Medscape updates on clinical studies (Medical Professionals' Continuing Ed site) re: FM

canadjineh

In my inbox on March 6/2015 re: FM & prevalence of cardiovascular problems. Complete quote from Study Discussion: (I put some of the main points in bold type here)

"Journal of Clinical Rheumatology

Fibromyalgia and Nondipper Circadian Blood Pressure Variability
Salih İnal, MD, Esra Erkol İnal, MD, Gülay Ulusal Okyay, MD, Gökhan Tuna Öztürk, MD, Kürşad Öneç, MD, Galip Güz, MD
Disclosures
J Clin Rheumatol. 2014;20(8):422-426.

Abstract

Background and Objectives Aberrant circadian rhythm with persistent nocturnal sympathetic hyperactivity has pointed out malfunctioning autonomic nervous system in fibromyalgia (FM) patients. This is a common pathogenesis shared also by patients with nondipping blood pressure (BP) pattern. Therefore, we aimed to investigate the frequency of nondipping BP pattern in normotensive women with newly diagnosed FM compared with healthy women.

Methods Sixty-seven normotensive women with new diagnosis of FM and 38 age-matched healthy volunteer women were recruited into the study. All subjects underwent 24-hour ambulatory BP monitoring on a usual working day. Individuals were defined as "dippers" if their nocturnal BP values decreased by more than 10% compared with daytime values; defined as "nondippers" in case of a decline less than 10%. Serum creatinine, fasting blood glucose, cholesterol levels, albumin, and thyroid-stimulating hormone levels were assessed.

Results Ambulatory measurements showed significantly higher diastolic BP values in patients with FM for both average of 24-hour recordings. Patients with FM had significantly lower systolic (9.1 ± 3.9 vs 11.5 ± 4.9, P = 0.010) and diastolic dipping ratios (12.3 ± 6.1 vs 16.1 ± 6.4, P = 0.004). The number of nondippers in the FM group was significantly higher than that of controls for both systolic (66% vs 34%, P = 0.002) and diastolic BP measurements (42% vs 21%, P=0.031). Patients with FM were 3.68 times more likely to be systolic nondipper and 2.69 times more likely to be diastolic nondipper.

Conclusions We have demonstrated a significant relationship between FM and nondipping BP pattern, and we suggest that nondipping profile, which has been closely associated with cardiovascular morbidity, may appear as an additional risk factor in patients with FM.

Results

The demographic characteristics and laboratory data of the subjects are shown in Table 1. Fibromyalgia patients and healthy subjects were similar regarding age, BMI, fasting blood glucose levels, smoking status, and resting heart rates (all P > 0.05). Total cholesterol and LDL cholesterol levels were significantly higher in patients with FM compared with control subjects (both P <0.05).

Office and ambulatory BP measurements of the study participants are presented in Table 2. There was no difference in office BP measurements between patients with FM and control subjects. Ambulatory measurements showed significantly higher diastolic BP values in patients with FM for both average of 24-hour recordings (70.9 ± 6.7 vs 68.3 ± 5.3, P = 0.025) and nocturnal recordings (65.3 ± 7.5 vs 60.8 ± 5.8, P = 0.002). In addition, patients with FM had significantly lower systolic (9.1 ± 3.9 vs 11.5 ± 4.9, P = 0.010) and diastolic dipping ratios (12.3 ± 6.1 vs 16.1 ± 6.4, P = 0.004).

Under the lights of this study, we could consider that some systemic adverse effects might be appearing in the course of FM, besides the well-known discomforts in daily lives of the affected persons. The clinical outcomes such as left ventricular hypertrophy, coronary artery diseases, and renal damage are more prevalent in nondipper hypertensive subjects compared with those having normal circadian profile.[9,10,31–33] Of particular interest, nondipper pattern was reported to be associated with higher target organ damage even in normotensive subjects.[34] Regarding the prevention of complications, the treatment strategies based on ambulatory BP measurements have been found superior to the ones based on traditional office BP measurements.[35] However, the current hypertension guidelines do not recommend the routine use of ambulatory BP measurements in clinical practice and limit its application to a few particular cases.[13,36] In our study, we particularly identified distorted nocturnal BP profile by ambulatory recordings in patients with FM for whom the daytime office BP measurements were completely in normal limit. Given the adverse prognostic effects of nondipping pattern, we suggest that ambulatory BP monitorization should take place in the clinical evaluation of patients with FM.

Another finding of this study was the higher total cholesterol and LDL cholesterol levels of patients with FM compared with our control subjects. Hypercholesterolemia, particularly high LDL cholesterol levels, is a well-known traditional risk factor, and there is extensive evidence for LDL cholesterol reduction as a target for decreasing cardiovascular risk. Consistent with our results, total cholesterol and LDL cholesterol levels of women with FM were found to be significantly higher than that of the control subjects in a previous study conducted by Gurer et al.[37] Interestingly, in a more recent trial, a significant correlation was reported between FM symptoms and total cholesterol levels in patients with FM.[38]The exact mechanism of any relation between hypercholesterolemia and FM is unknown, but reduced physical activity caused by painful conditions might be a causative factor. Besides nondipper BP pattern, such negative effects on the lipid profile may also play a role in the possible development of accelerated atherosclerosis in patients with FM.

Previously, several studies have pointed out the effects of smoking status, ethnicity,[39] obesity,[40] and hypothyroidism[11] over the development of nondipping status. In our study, patients with FM and control subjects were similar in terms of BMI, serum TSH levels, and smoking status. In addition, all participants were female and from the same ethnicity. Therefore, we can suggest that the impact of FM over the development of nondipping status was independent of possible confounders.

Although the present study is the first to demonstrate the relationship between FM and impaired diurnal rhythm of BP, it has several limitations. First limitation is somewhat small number of the study population. A considerable number of newly diagnosed patients with FM have been excluded because of systemic diseases, which could have potential effects on circadian BP variability. Second, we did not record any disease severity measurement, and we could not put forward any mechanism in the casual pathway of this relationship. Third, our study was of cross-sectional design and lacks long-term clinical follow-up. We have not investigated the impact of FM on circadian BP variability in prospective manner. Finally, all study participants were female and from the same ethnicity; however, this point may be taken as an advantage as previously mentioned.

In conclusion, we have demonstrated a significant relationship between FM and nondipping BP pattern. We can consider that nondipping profile, which is closely associated with cardiovascular morbidity, may appear as an additional risk factor in patients with FM. Further studies are warranted to confirm this relationship, to elucidate the pathogenetic mechanisms, and to show the impact of effective therapies on circadian BP profile."


Hope some others found this enlightening/helpful...

canadjineh

March 23/2015 article and references on Medscape
Gluten-free Diet in the Management of Patients With Irritable Bowel Syndrome, Fibromyalgia and Lymphocytic Enteritis
Umberto Volta
Disclosures
Arthritis Res Ther. 2014;16(505)

Authors and Disclosures
Umberto Volta

Department of Medical and Surgical Sciences, University of Bologna, via Massarenti 9, Bologna 40138, Italy

Correspondence
umberto.volta@aosp.bo.it
Competing interests
The author declares that he has no competing interests.

"An evaluation of the effect of 1 year of a gluten-free diet was performed in patients with irritable bowel syndrome and fibromyalgia syndrome displaying lymphocytic enteritis. Gluten withdrawal produced a slight but significant improvement of the functional symptoms, suggesting that gluten might be partly responsible for this clinical picture. This hypothesis should be confirmed by a double-blind placebo-controlled trial since it cannot be ruled out that the studied patients displayed a subjective sensation of improvement due to the placebo effect of gluten withdrawal. Further investigations are needed before recommending gluten withdrawal in patients with fibromyalgia and lymphocytic enteritis.

In their paper published in a recent issue of Arthritis Research and Therapy, Rodrigo and colleagues evaluated the effect of 1 year of a gluten-free diet on the clinical evolution of irritable bowel syndrome (IBS) plus fibromyalgia syndrome (FMS) in patients with lymphocytic enteritis (LE).[1] The study sample included 97 adult females with IBS and FMS, of whom 58 had LE and the remaining 39 had a normal intraepithelial lymphocytic (IEL) count. All subjects fulfilled the Rome III criteria for IBS and the American College of Rheumatology 1990 criteria for FMS and none of them satisfied the diagnostic criteria for celiac disease diagnosis (absence of villous atrophy and negativity for tissue transglutaminase antibodies).

IBS and FMS are two chronic functional disorders that are found in a high number of people in the general population and are frequently detected in the same subject.[2] A subset of patients complaining of IBS and FMS displays LE, a morphological finding that by itself is not specific for celiac disease, also being found in many other pathological conditions such as food allergy, autoimmune disorders, Helicobacter pylori infection, nonsteroidal anti-inflammatory drug treatment and common variable immunodeficiency.[3]

The spectrum of gluten-related disorders has recently acquired a new syndrome, defined as nonceliac gluten sensitivity according to the criteria established in the two Consensus Conferences held in London and Munich.[4] This new clinical entity is characterized by IBS-like symptoms and several extraintestinal manifestations occurring after gluten ingestion in patients without celiac disease and wheat allergy. In a recent prospective multicenter survey of 486 patients with nonceliac gluten sensitivity, IBS and FMS were respectively detected in 47% and 31% of cases and about one-third of these patients had LE.[5]

Along with IBS-related and FMS-related symptoms, the patients studied by Rodrigo and colleagues also showed other manifestations resembling the clinical picture of nonceliac gluten sensitivity such as skin rash, cognitive dysfunction, headache, numbness, anxiety and depression.[1]

In Rodrigo and colleagues' paper, the gluten-free diet produced a slight but significant improvement of both IBS-related (chronic abdominal pain, changes in intestinal habit, bloating) and FMS-related symptoms (chronic widespread pain, generalized tender points, fatigue and restless sleep) in the LE subgroup versus the non-LE subgroup. These results stress the potential role of gluten as a trigger of the clinical manifestations of IBS and FMS and indicate that LE might be useful to identify those patients who potentially benefit from gluten withdrawal. One relevant limitation of this study is the lack of a double-blind placebo-controlled challenge, which is the only procedure to confirm the role of gluten proteins in the development of these clinical manifestations. Indeed, it cannot be ruled out that some patients displayed a subjective sensation of improvement due to the placebo effect of a gluten-free diet.[6] The search for antigliadin antibodies could be of help to elucidate whether gluten can be partly responsible for the clinical picture observed in Rodrigo and colleagues' patients. Indeed, antigliadin antibodies (particularly those belonging to the IgG class) are the only marker observed in patients with symptoms elicited by gluten ingestion, being positive in more than 50% of cases.[7] These antibodies are not specific for gluten-related symptoms, but their finding in patients with symptoms potentially evoked by gluten ingestion should be regarded as an indication for a gluten-free diet trial in patients with LE.[8] Antigliadin antibodies of the IgG class are closely related to the gluten-induced symptoms and tend to disappear very quickly (within a few weeks) together with the remission of symptoms after a gluten-free diet.[9]

An interesting finding emerging from the Spanish study is that about 20% of IBS/FMS patients with LE had relatives with celiac disease, whereas no familial case of celiac disease was observed among patients without LE.[1] In the same guise, familial cases of FMS were found, although to a lesser extent, only in the group with LE (7%). These data suggest that first-degree relatives of IBS/FMS patients with LE should be carefully investigated for the possible presence of undetected cases of celiac disease and FMS. For LE, the mean IEL number reported in Rodrigo and colleagues' paper was 35/100. This result confirms that LE found in gluten-sensitive patients is mild, with a lower mean IEL number than that usually observed in celiac disease patients (usually >40/100).[10]

The caution in the conclusions of Rodrigo and colleagues' study is appreciable and shareable. A gluten-free diet is not appropriate in patients with IBS/FMS with normal intestinal mucosa (normal IEL count). Moreover, although the reported results suggest a significant improvement of symptomatology after a gluten-free diet in the LE subgroup, further studies including double-blind placebo-controlled trials are needed before proposing gluten withdrawal in IBS/FMS patients with LE.

References

1.Rodrigo L, Blanco I, Bobes J, de Serres F: Effect of one year of a gluten-free diet on the clinical evolution of irritable bowel syndrome plus fibromyalgia in patients with associated lymphocytic enteritis: a case–control study. Arthritis Res Ther 2014, 16:421.

2.Whitehead WE, Palsson O, Jones KR: Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology 2002, 122:1140–1156.

3.Brown I, Mino-Kenudson M, Deshpande V, Lauwers GY: Intraepithelial lymphocytosis in architecturally preserved proximal small intestinal mucosa: an increasing diagnostic problem with a wide differential diagnosis. Arch Pathol Lab Med 2006, 130:1020–1025.

4.Catassi C, Bai JC, Bonaz B, Bouma G, Calabrò A, Carroccio A, Castillejo G, Ciacci C, Cristofori F, Dolinsek J, Francavilla R, Elli L, Green P, Holtmeier W, Koehler P, Koletzko S, Meinhold C, Sanders D, Schumann M, Schuppan D, Ullrich R, Vécsei A, Volta U, Zevallos V, Sapone A, Fasano A: Non-celiac gluten sensitivity: the new frontier of gluten related disorders. Nutrients 2013, 5:3839–3853.

5.Volta U, Bardella MT, Calabrò A, Troncone R, Corazza GR: Study Group for Non-Celiac Gluten Sensitivity: An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity. BMC Med 2014, 12:85.

6.Godlee F: Gluten sensitivity: real or not? BMJ 2012, 345:e7982.

7.Volta U, Tovoli F, Cicola R, Parisi C, Fabbri A, Piscaglia M, Fiorini E, Caio G: Serological tests in gluten sensitivity (nonceliac gluten intolerance). J Clin Gastroenterol 2012, 46:680–685.

8.Verdu EF: Can gluten contribute to irritable bowel syndrome? Am J Gastroenterol 2011, 106:516–518.

9.Caio G, Volta U, Tovoli F, De Giorgio R: Effect of gluten-free diet on immune response to gliadin in patients with non-coeliac gluten sensitivity. BMC Gastroenterol 2014, 12:85.

10.Volta U, Caio G, Tovoli F, De Giorgio R: Non-celiac gluten sensitivity: questions still to be answered despite an increasing awareness. Cell Mol Immunol 2013, 10:383–392.

canadjineh

italics are my comments

New Article on Aug 25th re:
Juvenile Fibromyalgia: Intensive Therapy Relieves Pain

Children with fibromyalgia experienced significant improvements in pain and function without medications after an intensive program of physical therapy (PT), occupational therapy (OT), and psychosocial services, according to a new study. The improvements were still significant 1 year after completing the program.

David D. Sherry, MD, from the Division of Rheumatology at Children's Hospital of Philadelphia, and colleagues present their findings in an article published online July 21 in the Journal of Pediatrics.

"Our children with long-standing fibromyalgia exhibited significant improvement in nearly all of the functional and pain measures that we applied," the authors write.

The study enrolled 64 of 81 patients with juvenile fibromyalgia (median age, 16 years) who were already participating in an intensive musculoskeletal pain program. Most of the patients were white girls. The patients discontinued all their medications at enrollment.

Physical and occupational therapy involved 5 to 6 hours per day of therapeutic activities such as long-distance community ambulation and running up and down stairs, with the goal of reestablishing normal function and maximizing aerobic conditioning. In addition, patients participated 4 hours a week in cognitive and behavioral therapy one on one or in groups, along with art, music, and family therapies.

"Both the dose of PT/OT and the quality of the therapy differed from traditional PT/OT, in that we focused on desensitization and prolonged aerobics, strengthening, and functional activities individualized to the subjects, and did not inquire about pain or let pain or the fear of pain stop them," the authors write.

"We believe that this focus on function rather than pain helps children break the pain cycle and overcome the long-standing functional and pain limitations with which they presented."

The researchers used a pain visual analogue scale; the Pediatric Quality of Life Inventory, Team Report; a functional disability inventory; and other measures of ability to achieve and maintain normal functioning. The latter included the Bruce Treadmill Protocol, which consists of walking on a gradually accelerating treadmill for 21 minutes or until the patient is unable to continue.

The researchers tallied results at baseline, on completion of the intensive program, and 1 year later.

At the end of the program, the mean pain score decreased significantly from program entry (from 66 of 100 to 25 of 100; P = .001). One third of patients reported no pain at 1 year after program completion.

The mean Bruce Treadmill Protocol time fell slightly over the year after program completion, but scores remained significantly better than those at program entry (P < .001) and remained at or above the 90th percentile for age and sex compared with below the 25th percentile at enrollment.

Scores improved significantly initially and remained stable or improved at 1 year for all Pain Stages of Change Questionnaire, adolescent version subset; the Pediatric Quality of Life Inventory, Teen Report; and the Bruininks-Oseretsky Test of Motor Performance, Second Edition.

Fibromyalgia is an incurable musculoskeletal disorder and pain syndrome of unknown etiology and elusive treatment solutions. Defined by persistent, amplified, widespread pain associated with five or more of 18 trigger points, it affects between 2% and 6% of the pediatric population. More than 90% of patients report persistent pain and sleep disturbance, with persistent symptoms into adulthood.


"[T]hese children had long-standing pain that did not remit with less-intensive therapy," the authors note.

Bottom line, they say: "Children with fibromyalgia can be successfully treated without the use of medications and can regain normal function, achieve remission or marked reduction of pain, and experience increased quality of life with an interdisciplinary approach that uses much more intensive [physical and occupational therapy] than is common in most pain programs, along with cognitive, behavioral, and other psychosocial supports."

Funded by the Children’s Hospital of Philadelphia and the Snider Family. The authors have disclosed no relevant financial relationships.

J Pediatrics. Published online July 21, 2015. Abstract

I think this would work for adults too (seems to in my case, anyhow.)

canadjineh

Fibromyalgia Linked to Deficiencies in RBC Magnesium, IGF-1

Nancy A. Melville
| September 22, 2015

NATIONAL HARBOR, MD — Patients with fibromyalgia show deficiencies in red blood cell (RBC) magnesium and insulin-like growth factor 1 (IGF-1), a small study shows, suggesting potential clues to underpinnings of the condition and avenues for treatment.
"In identifying a comorbidity that can be objectively verified, you can let patients know that one of the reasons they could be having problems is because of these abnormal levels. Restoring those levels to where they should be, we have found, can truly turn people's lives around — they have more stamina and more energy," Dr Romano said.

Their research was presented here at the American Academy of Pain Management (AAPM) 2015 Annual Meeting.

Comorbidities Related?

Having reported on low RBC magnesium levels among his patients with fibromyalgia back in the 1990s, Dr Romano noted some previous studies also linking low IGF-1 to the condition and sought to further investigate whether the two comorbidities were often related.

He enrolled 60 patients with confirmed fibromyalgia: 10 men with a mean age of 49.5 years and 50 women with a mean age of 42.8 years.

In tests evaluating IGF-1, the patients as a group had a mean IGF-1 level of 59.33 ng/dL, which is lower than the mean of 235 ng/dL that would be expected according to calculations of patients' ages. IGF-1 levels are age dependent.

Measures of RBC magnesium levels were also taken on the same day, and results as a group showed a mean magnesium level of 4.49 mg/dL, lower than the mean level in a control group of 12 osteoarthritic patients and the laboratory standard of 5.5 mg/dL.

"The findings suggest that if you determine that fibromyalgia patients have low magnesium levels, you might want to check IGF-1," Dr Romano said.

He noted that in referring such patients to an endocrinologist, the results have been consistent.
"When I suspect a patient's IGF-1 levels are low, I send them to an endocrinologist for confirmation and they will do the intravenous GHRH [growth hormone–releasing hormone]-arginine stimulation test," he explained.
"The typical response is a peak and then the level comes down, but in the vast majority of fibromyalgia patients it's just a flat reading, with no response."

Treatment with growth hormone to restore normal levels typically starts with low dose, 0.2 mg, of subcutaneous injections daily for several months, with increased titration if levels are not restored within several months, Dr Romano said.

Although the study is small, Dr Romano urged clinicians to consider such factors when struggling with fibromyalgia management.

"The take-home message is to keep looking," he said. "Fibromyalgia patients tend to have numerous comorbidities and they may be related."

Studies that have also linked IGF-1 levels to fibromyalgia include a randomized, double-blind, placebo-controlled study published in 1997 in the American Journal of Medicine, which showed significant overall improvements in fibromyalgia symptom scores after IGF-1–deficient women were treated with daily growth hormone injections.

The "Future" of Chronic Pain

Pain specialist Forest Tennant, MD, PhD, from the Veract Intractable Pain Clinic in West Covina, California, who has also explored the role of hormones in chronic pain and presented a talk on the topic at the meeting, noted that, aside from the few earlier studies, the role of growth hormone in fibromyalgia has not been extensively explored.


"When it comes to pain, we're not entirely certain what growth hormone does, but that it affects mainly hard tissue such as bone cartilage," he told Medscape Medical News.

"But we've been extensively studying human chorionic gonadotropin and that looks like it works more importantly in the nervous system and really seems to be becoming an essential compound."

"I'm glad they're studying this, however, because [hormone involvement] is the future of chronic pain, there's no question about it."

Dr Romano has disclosed no relevant financial relationships. Dr Tennant receives speaker's bureau fees from Ethos Labs, Regenesis Biomedical, and INSYS Therapeutics.

American Academy of Pain Management (AAPM) 2015 Annual Meeting. Presented September 19, 2015.

***********************************************************************
PubMed studies below on magnesium and Fibromyalgia.

Please excuse the lack of links, but you can just search the titles in PubMed.

1: Moorkens G, Manuel y Keenoy B, Vertommen J, et al. Magnesium deficit in a sample of the
Belgian population presenting with chronic fatigue. Magnes Res 1997;10:329-37.
2: Ng SY. Hair calcium and magnesium levels in patients with fibromyalgia: a case center
study. J Manipulative Physiol Ther 1999;22:586-93.
3: Red blood cell magnesium and chronic fatigue syndrome?IM Cox, MJ Campbell, D Dowson -
The Lancet, 1991 - Elsevier
4: A connection between magnesium deficiency and aging: new insights from cellular
studies.?Killilea DW, Maier JA., Magnes Res. 2008 Jun;21(2):77-82.
5: Effects of pH and free Mg2+ on the Keq of the creatine kinase reaction and other
phosphate hydrolyses and phosphate transfer reactions.
Lawson JW, Veech RL. J Biol Chem. 1979 Jul 25;254(14):6528-37.
6: Magnesium homeostasis during high-intensity anaerobic exercise in men.
Deuster PA, Dolev E, Kyle SB, Anderson RA, Schoomaker EB.
J Appl Physiol. 1987 Feb;62(2):545-50.
7: Molecular components of vertebrate Mg2+-homeostasis regulation.?Schmitz C, Deason F,
Perraud AL. Magnes Res. 2007 Mar;20(1):6-18.

deeschange

Great information

canadjineh

thanks, @deeschange I'll add more as they come to my inbox.

canadjineh

New study abstract:

Pelvic Floor and Urinary Distress in Women With Fibromyalgia

Kim Dupree Jones, PhD, FNP, FAAN; Charlene Maxwell, DNP, FNP; Scott D. Mist, PhD; Virginia King, MD; Mary Anna Denman, MD; W. Thomas Gregory, MD
Disclosures
Pain Manag Nurs. 2015;16(6):834-840.

Fibromyalgia (FM) patients were recently found to have more symptom burden from bothersome pelvic pain syndromes than women seeking care for pelvic floor disease at a urogynecology clinic. We sought to further characterize pelvic floor symptoms in a larger sample of FM patients using of validated questionnaires. Female listserv members of the Fibromyalgia Information Foundation completed an online survey of three validated questionnaires: the Pelvic Floor Distress Inventory 20 (PFDI-20), the Pelvic Pain, Urgency and Frequency Questionnaire (PUF), and the Revised Fibromyalgia Impact Questionnaire (FIQR). Scores were characterized using descriptive statistics. Patients (n = 204 with complete data on 177) were on average 52.3 ± 11.4 years with a mean parity of 2.5 ± 1.9. FM severity based on FIQR score (57.2 ± 14.9) positively correlated with PFDI-20 total 159.08 ± 55.2 (r = .34, p < .001) and PUF total 16.54 ± 7 (r = .36, p < .001). Women with FM report significantly bothersome pelvic floor and urinary symptoms. Fibromyalgia management should include evaluation and treatment of pelvic floor disorders recognizing that pelvic distress and urinary symptoms are associated with more severe FM symptoms. Validated questionnaires, like the ones used in this study, are easily incorporated into clinical practice.

Like FM, chronic pelvic pain and bladder pain have been characterized by some as functional or sensory hypersensitivity pain disorders for which there are conflicting etiologic theories and lack of standardized treatments (Clemens, Elliott, Suttorp, & Berry, 2012; Clemens et al., 2014; Adams & Denman, 2011). Pelvic floor disorders negatively influence a woman's activities of daily living, sexual function, bowel and bladder function, and overall quality of life. Despite their high prevalence and negative impact, little known about the relationship between pelvic/bladder symptoms and FM severity. The purpose of this study was to characterize pelvic floor and urinary symptoms in patients with FM. A secondary aim was to describe the strength of the relationship between pelvic floor and urinary symptoms with the total impact of FM.

Demographic and clinical data were collected via an investigator-designed questionnaire and the Revised Fibromyalgia Impact Questionnaire (FIQR). The FIQR is a validated questionnaire commonly used in clinical practice to measure the FM patient's current level of negative impact from FM symptoms and physical function in the context of three domains: level of function (range 0–30), overall impact (range 0–20), and symptoms (range 0–50). Symptom questions assess pain, fatigue, disrupted sleep, muscle tenderness, stiffness, memory, anxiety, depression, balance, and sensitivity to light/noise/smell. Higher scores on the FIQR total score (range 0–100) indicate greater negative impact of FM on overall functioning; an FIQR total score of 0–39 represents mild symptoms, 40–58 represents moderate symptoms, and 59–100 represents severe impact on overall functioning (Bennett et al., 2009).

Of the 500 invitations e-mailed to participate, 483 were successfully received by potential participants. A total of 204 potential respondents completed the survey (42% response rate). Of those, 177 had complete data. All data were preprocessed for completeness and appropriate response ranges. The data were analyzed using Stata software (Stata Statistical Software, Release 13, StataCorp LP, College Station, TX). The mean age was 52.3 ± 11.4 years, with a history of 2.5 ± 1.9 births. Patients were mostly married (71%). As is reflective of the Pacific Northwest, 92% were Caucasian. Additional data indicated that most reported FM symptoms for >10 years (69%), with almost half (45%) having received a diagnosis >10 years ago. Almost all reported problems with concentration or memory (94%); more than half reported co-morbidities, including chronic fatigue syndrome (56%), chronic headache (74%), temporomandibular joint disorders (55%), dry eyes/dry mouth (74%), balance problems (73%), restless leg (55%), anxiety symptoms (63%), and depressive symptoms (79%). With regard to pelvic/urinary/abdominal symptoms, 80% endorsed having irritable bowel/gastrointestinal (GI) problems, whereas only 39% were diagnosed with irritable bladder or interstitial cystitis
Mean responses to the PFDI-20 were 159.1 ± 55.2. In addition, the colorectal distress was the most bothersome subscale at 58.2 ± 22.5. The mean total score of the PUF was 16.5 ± 7.0. The symptom score was 10.3 ± 4.5; mean bother score was 6.3 ± 3.1 (Table 2). The majority of patients indicated that they experienced bladder or pelvic pain at least occasionally (93%), with greater than half reporting symptoms on a usual basis. The majority of participants reported feelings of urinary urgency after voiding (93%), with greater than half reporting that they experience this on a usual basis.

The revised Fibromyalgia Impact Questionnaire was 57.2 ± 15.0, indicating moderate to severe FM impact. Symptom severity was 28.2 ± 7.3 with a pain score of 5.5 ± 2.0. Five FM symptoms were ranked as more severe than pain. The most severe symptoms were sleep problems and fatigue, followed by stiffness; sensitivity to odors, cold, bright light, and loud noise; and tenderness to touch (Table 3).

In general, as FM impact was worse, pelvic and bladder symptoms were also worse. Most notably, the FIQR symptom subscale was positive correlated with PFDI-20 total (r = .34, p < .001). The CRADI and the FIQR symptom subscale were similarly correlated (r = .34, p < .005). The PUF total was also correlated positively with the FIQR symptom subscale (r = .36, p < .001).

Continued next post as this is too long for one post in MFP...

canadjineh

Continuation of study abstract from previous post...

The findings of this study support findings in the literature that FM is commonly associated with self-reported co-morbidities such as irritable bowel or gastrointestinal problems, depressive symptoms, anxiety symptoms, temporomandibular dysfunction, chronic pelvic pain and irritable bladder (Clauw, 2014; Mease, 2009). The following data, however, are novel to the literature: (1) the majority (93%) of women indicated that they experience bladder or pelvic pain at least occasionally, with more than half reporting that they experience discomfort on a usual basis, and (2) FIQR scores positively correlated with PFDI-20 (total and CRADI subscale) and PUF scores, indicating that among those with more severe FM impact, there is an increased presence and severity of urinary and pelvic floor distress symptoms.

Newly published data report that women with FM have 50% greater pelvic floor symptoms compared with matched women without FM who were evaluated at a urogynecology clinic for pelvic floor distress (Adams et al., 2014). The women with FM had significantly worse pelvic floor distress than age-matched women without FM (PFDI scores 145.0 [63.3] versus 110.5 [64.5; p = .005]). Patients in Adams' study were of similar age, parity, and race compared with patients in our study. These authors also report physical examination data. The most notable were that most FM patients had levator myalgia on examination, OR 3.8 (95% CE 1.3, 9.1). Patients in our cohort, compared with Adams' FM cohort, reported greater levels of total pelvic floor distress (159.1 [55.2] vs. 145.0 [63.3]) and colorectal symptoms (58. 2 [22.5] vs. 37.9 [22.6]). Both groups had similar levels pelvic organ prolapse symptoms (50.5 [27.3] vs. 51.6 [26.9]). Adam's sample had greater levels of urogenital symptoms (48.1 [29.0] vs. 55.4 [29.1]).

We compared these data to data from the present study and also found that in a simple linear regression controlling for parity, women with FM reported pelvic floor symptoms at a severity greater than women presenting to a urogynecology practice despite being the same age (p < .01).

There is evidence that patients with urologic chronic pelvic pain syndrome are more likely to suffer from bothersome symptoms in other body systems similar to those found in FM compared with healthy controls (Lai, North, Andriole, Sayuk, & Hong, 2012). Additionally, women with FM are more likely to have had a hysterectomy compared with the general population, yet hysterectomy may not improve chronic pelvic pain in women with FM (Pamuk, Donmez, & Cakir, 2009; Santoro, Cronan, Adams, & Kothari, 2012; ter Borg, Gerards-Rociu, Haanen, & Westers, 1999).. Similarly patients with chronic pelvic pain compared with those without recently were found to be at increased risk of not improving or even worsening after undergoing transvaginal mesh revision (Danford, Osborn, Reynolds, Biller, & Dmochowski, 2015).

Based on responses from the PUF questionnaire, we found that the majority (93%) of women with FM indicated that they experience bladder or pelvic pain at least occasionally, with more than half reporting that they experience discomfort on a usual basis. This is interesting because only 39% self-report a diagnosis of irritable/pain bladder or interstitial cystitis. Perhaps nonurogyencologic providers are less confident in diagnosing specific bladder disorders. Although this study does not address whether the women in our FM cohort fit the diagnostic criteria for interstitial cystitis, the results do suggest that women with FM should be evaluated for these comorbidities, including interstitial cystitis. This finding is consistent with previous studies linking FM and interstitial cystitis as shared comorbidities with possible shared pathophysiology. De Araujo et al. (2008)) used both validated questionnaires and urodynamic assessment to evaluate symptoms of urinary distress among the FM population and found that symptoms of lower urinary tract distress such as frequency and incontinence were statistically more prevalent among the FM population with known lower urinary tract symptoms (LUTS) (n = 51) compared with a group with LUTS but without FM (n = 50) (de Araujo et al., 2008). Objectively, urodynamic studies revealed that the FM population had higher detrusor overactivity compared with the LUTS-only group and significantly worse quality of life as evaluated by validated questionnaire.

In 1997 a study evaluating pain threshold and FM symptoms in people with FM (n = 60), in people with interstitial cystitis without FM (n = 30), and in healthy controls (n = 30) found that both the FM and interstitial cystitis groups exhibited increased pain sensitivity to both tender points and control points compared with the healthy control group (Clauw et al., 1997). Furthermore, both the FM and interstitial cystitis groups reported higher levels of FM symptoms compared with the healthy controls.
Our findings may contribute to the growing body of literature suggesting that pelvic floor distress could play a significant role in FM as a potential pain generator that perpetuates and exacerbates chronic pain and hyperalgesia. Given the high prevalence of pelvic distress among the FM group, this could also indicate that those diagnosed with a pelvic floor disorders should also be evaluated for FM and vice-versa. Co-investigators on this study report that screening for undiagnosed FM is not typically completed in the urogynecologic evaluation.
It is imperative to learn if women with FM have differing outcomes from the treatment of pelvic floor disorders than women without FM. Ultimately, clinicians need to know if early recognition and treatment of pelvic floor disorders among women with FM could improve their overall FM functioning and decrease pain.


End of abstract.

canadjineh

Something to think about... is your FM actually Systemic Lupus Erythematosis? I have cut out a couple pages of very comprehensive scientific lingo regarding the testing parameters - best to check with your physician as they may be able to access the full site for more info. This test is so far only available in the US.

Systemic Lupus Erythematosus and Primary Fibromyalgia Can Be Distinguished by Testing for Cell-bound Complement Activation Products

Daniel J Wallace; Stuart L Silverman; John Conklin; Derren Barken; Thierry Dervieux
Disclosures
Lupus Sci Med. 2016;3(1)

Objective: We sought to establish the performance of cell-bound complement activation products (CB-CAPs) as a diagnostic tool to distinguish primary fibromyalgia (FM) from systemic lupus erythematosus (SLE).

Introduction

Systemic lupus erythematosus (SLE) remains the prototypical autoimmune systemic disease in which hyperactivity of the immune system and production of autoantibodies lead to a variety of symptoms including chronic pain, arthralgia, fatigue, morning stiffness and, most importantly, damage in key organs including the kidney and central nervous system.[1] Because SLE is a serious chronic condition associated with significant mortality and burden to the healthcare system, early diagnosis and initiation of appropriate therapy (eg, immunosuppressants, antimalarials and corticosteroids) is important.[2] However, many patients with SLE present with symptoms that are non-specific, do not fulfil formal classification criteria of the disease (eg, American College of Rheumatology (ACR) criteria)[3] and thus may remain undiagnosed for a prolonged time.

This challenge in correctly identifying and diagnosing SLE is further complicated by the low prevalence of the disease (~1/1000 in the USA) in comparison with other more prevalent rheumatic disorders whose symptoms mimic those of SLE[4,5] such as rheumatoid arthritis, and primary fibromyalgia (FM).[6] In particular, SLE can sometimes be difficult to identify and differentiate from FM, because the prevalence of FM is at least 10-fold greater than that of SLE, and most symptomatic patients (eg, with chronic widespread pain) are initially evaluated by primary care physicians who lack expertise in diagnosing the disease.[7] Moreover, FM is a non-inflammatory pain syndrome,[8,9] whereas SLE is a systemic inflammatory illness and thus there a significant treatment and prognostic differences between those two conditions.

Traditionally, clinicians distinguish SLE from other illnesses by a combination of clinical history, demographic, age at disease onset together with examination and the determination of laboratory tests that include antinuclear antibody (ANA) among other SLE-specific autoantibodies. ANA is a sensitive test for SLE, and more than 95% of SLE are ANA positive during the course of their disease.[10] However, about 14% of the general population is also ANA positive,[11] and 15%–25% of patients with FM have been reported to be positive for ANA.[12,13] It follows that the risk of misdiagnosing SLE could be significant, as the vast majority of patients presenting with symptoms mimicking SLE will turn out to have FM and not SLE, even if the ANA test is positive. Other diagnostic tests such as anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) can be helpful in diagnosing SLE, but their utility is limited by their poor sensitivity.

The value of cell-bound complement activation products (CB-CAPs, including C4d deposited on erythrocytes (EC4d) and B-lymphocytes (BC4d) in the differential diagnosis of SLE compared with other autoimmune rheumatic diseases) has been established previously.[14–17] We recently combined these CB-CAP biomarkers with standard rheumatic disease autoantibodies into a multi-analyte assay with algorithm (MAAA). The CB-CAPs in MAAA have demonstrated improved sensitivity compared with anti-DNA antibodies and low serum levels of C3 and C4 for the diagnosis of SLE.

Because SLE is far less prevalent than FM, the vast majority of patients presenting with non-specific muscular, articular and constitutional symptoms will have FM and not SLE.[32] Many clinicians rely on ANA testing to identify SLE but the ANA test has severe limitations including a significant number of false-positives. While these limitations are recognised by rheumatologists, many primary care physicians may be unaware of these drawbacks and inappropriate referral of ANA-positive patients can follow the initial clinical assessment. Because of its high specificity, the CB-CAPs in MAAA could potentially facilitate the appropriate referral of true patients with SLE to the rheumatologist.
We believe that this practical tool with enhanced performances compared with traditional complement measure (C3/C4) can help establish a diagnosis for SLE. Moreover it is a practical measure of complement activation as blood specimen can be shipped overnight from the physician office to the laboratory. In summary, our data indicate that the CB-CAPs in MAAA test has utility in differentiating SLE from FM, and the value of the test is particularly significant among subjects that are ANA positive.

canadjineh

Clinical Rheumatology had articles on FM and Chronic Widespread Pain Syndrome in Autoimmune Thyroid Disease. 2014 &2015. Behooves us all to get a FULL PANEL Thyroid test including all the antibodies. My thyroid T3 T4 etc were all in the 'normal' range, but obviously not normal for me as my antibodies show at 1100 and they should be under 66...
Something to think about....

canadjineh

Hi all: Finally another MedScape article in my inbox that is an adjunct to FM issues with sleep/autoimmune diseases.

Key Primary Care Takeaways: Digestive Disease Week 2016
David A. Johnson, MD

Sleep Fragmentation and the Gut Microbiome

"The last study that I wanted to bring to your attention was a very fascinating study looking at the effects of sleep fragmentation on the gut microbiome.[12] You can't pick up a journal of any sort, primary care or specialty, and not see something about the gut microbiome.

This particular study looked at the effects of sleep on the gut microbiome and potential effects on immune function. This was a mouse study where they fragmented the sleep of mice and they looked at the microbiome, comparing with a control population of mice without sleep fragmentation. What is very interesting is that there is actually a circadian rhythm in the gut. In the course of the normal day, there is undulation, but a return to baseline from the day before. When they fragmented the sleep of these mice, they actually inverted this rhythm. Instead of a nice undulating clock-like mechanism, they found profound dysbiosis. We know that sleep fragmentation changes gut permeability, but we also can say that the gut is the largest immune system. They also looked at the mesenteric lymph nodes and their gene arrays that encode for the integrity of the gut wall—so, cytokines and chemokines that upregulate the integrity of the gut wall. These gene arrays were all inhibited. There was a major reduction in their viability, and they were basically downregulated.

Certainly when talking about immune function, we need to remember to talk to patients about sleep function. This is really a big wakeup call for us, as it starts to relate to gut dysbiosis and when patients are not responding to treatment. We need to take a good sleep history and talk to the patient about how they sleep and how they feel the next day when they get up. Sleep function is going to be really important as we start to tie this with the role of dysbiosis of the gut microbiome in virtually all diseases.

I wanted to give you a 30,000-foot view of the data that I thought were newsworthy from DDW 2016. You'll see more on these topics as the articles start to appear in in the literature, but I wanted to give you these updates that will hopefully steer you well in your next patient interactions."

canadjineh

Free Vimeo link to a very eye-opening documentary called "Genetic Roulette, the Gamble of Our Lives" interviewing MD's, oncologists, internists, pediatricians, allergists, and university med researchers about the effect of GMO foods on our gut health and immune system diseases.
free til midnight Jan 1
action.responsibletechnology.org/signup_page/grm58

canadjineh

Towards a Neurophysiological Signature for Fibromyalgia New Medscape article this month (4 pages long - I only posted one diagram and last discussion/abstract page)

AUTHORS AND DISCLOSURES
Marina López-Solàa,b,*, Choong-Wan Wooa,b, Jesus Pujolc, Joan Deusc,d,e, Ben J. Harrisonf, Jordi Monfortg and Tor D. Wagera,b

aDepartment of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA, bInstitute of Cognitive Science, University of Colorado Boulder, Boulder, CO, USA, cMRI Research Unit, Department of Radiology, Hospital del Mar, CIBERSAM G21, Barcelona, Spain, dDepartment of Clinical and Health Psychology, Autonomous University of Barcelona, Barcelona, Spain, eGuttmann Neurorehabilitation Institute, Autonomous University of Barcelona, Spain, fMelbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Victoria, Australia, gDepartment of Rheumatology, Hospital del Mar, Barcelona, Spain

*Corresponding author
Address: Department of Psychology and Neuroscience, University of Colorado Boulder, 345 UCB, Boulder, CO 80305, USA. Tel.: (303) 492 4299; fax: (303) 492 2967. E-mail address: marina.lopezsola@colorado.edu (M. López-Solà).

Conflict of interest statement
The authors declare no conflict of interests.




Brain Features Diagnostic of Fibromyalgia

"Combined Pain-multisensory Neural Classifier. Our study provides 3 distinct neural targets for objective patient characterization. A model combining: (1) enhanced responses in the NPSp, a pain-specific brain network, (2) a pattern of brain responses to painful pressure (FM-pain pattern), and (3) a pattern of extranociceptive multisensory responses, differentiated patients with FM vs healthy participants with 93% cross-validated accuracy. The 3 effects are theoretically significant. Stronger NPSp responses mediated mechanical hyperalgesia in FM and were associated with a trend to greater depression; stronger FM-pain and multisensory responses were associated with greater clinical pain. Thus, the combined model is most likely to be useful for clinical and translational purposes, although either feature might also be used alone. Although the NPSn was not significant in the final model, NPSn responses may nonetheless be important for assessing and understanding functional aspects of FM.

Pain-related Patterns. The NPSp pattern showed an augmented response in FM when the stimulus intensity was matched, but not when subjective pain was matched. It was a significant mediator of mechanical hypersensitivity in patients. Thus, NPSp responses are enhanced in patients in proportion to their augmented subjective experience of pressure-induced pain and are consistent with previous evidence supporting peripheral (Refs. 52,64,69) and central (Refs. 10,45,58,66) sensitization in FM. The current study cannot determine whether this enhancement reflects a change in the gain of the NPSp per unit stimulus intensity or simply reflects enhanced afferent input. Future studies could begin to disentangle these alternatives by testing multiple stimulus intensities in both patients and controls.

Rather than being limited to regions associated most strongly with emotional or evaluative aspects of pain (eg, anterior insula, ACC, lateral PFC), our findings showed a distributed enhancement of nociceptive processing affecting all major NPSp regions. In agreement with previous observations[25,56] and considering the validation properties of the NPS, the results provide evidence of augmented pain-specific responses in FM, consistent with peripheral/central sensitization.

NPSp responses were predictive of experimental pain but not ongoing clinical pain intensity, consistent with work showing that medial prefrontal-striatal systems rather than classic nociceptive systems are correlated with chronic low back pain.[6]

The NPSn pattern includes patterns within medial regions in which greater deactivation was previously associated with increased pain.[70] In this study, however, increased pain was associated with greater activations in healthy participants (specifically for the PCC/precuneus cluster) and patients with FM (for both the PCC/precuneus and the pgACC clusters). The pgACC showed increased activation specifically for patients with FM, in agreement with previous findings showing that chronic pain patients do not deactivate pgACC/medial PFC and/or surrounding regions of the "default mode" network as strongly as controls do (and sometimes show activation).[2,5,6,12,27,63,72] Conversely, the PCC/precuneus may activate in response to pressure-evoked pain in both healthy[4,16,43,65] and patient populations.[27,48,59,65] The value of "default mode" network regions as predictors of pain may therefore vary across pain modalities and pain patient groups. We discuss the issue in detail in Supplementary Text 3 (available online at http://links.lww.com/PAIN/A340).

The FM-pain pattern complements the NPS results by showing that FM was best characterized by concurrently augmented pain-evoked activation in regions that show an important role in sensory integration (anterior SII extending to middle insula) and "default mode" regions and reduced activation of the dorsolateral PFC, a region commonly found to play a role in pain and emotion regulation.[71,73] This pattern, which was (together with the multisensory) predictive of clinical pain in patients, also emphasizes the importance of some key regions that are not part of the NPS (and are important for self-related, motivational, and emotional regulation) as targets for future study in FM.

Supplementary analyses of medication use indicated that it was not sufficient to explain the relationship between the status of patients with FM and alterations in brain activity (Supplementary Text 4, available online at http://links.lww.com/PAIN/A340).

The multisensory pattern is the feature that most strongly discriminates patients with FM from healthy participants, with and without controlling for NPS and FM-pain responses, and contributes to predict clinical pain. Central processing of nonpainful sensory signals may be of particular importance in maintaining clinical pain in FM, in agreement with previous work.[29,42,58] Consistently, Harte et al.[29] very recently showed that fMRI data during a visual task could discriminate patients with FM vs healthy controls with 82% accuracy. The multisensory pattern shows early sensory cortical processing attenuation, which is consistent with reduced processing of fine sensory/discriminative properties of stimulus,[1,18,46,53] accompanied by amplification of sensory integration (in agreement with Ref. 29) and self-referential aspects of the response, including potential threat of harm.[17]

The FM-pain pattern could accurately classify patients vs controls using multisensory brain responses and vice versa, which may reflect a more global brain reorganization in FM that may be detected across a range of experimental conditions. Our study and others show overlapping brain functional alterations during rest and task performance in FM and other chronic pain conditions involving sensory integration (eg, Refs. 19,36,42,58), salience (Refs. 33,42,50,58,68), and default-mode network regions (eg, Refs. 6–8,49,50,58).

Overall, we have found an augmented NPSp response that is consistent with enhanced nociceptive processing, and partly mediates augmented mechanical pain, and, more broadly, evidence for central nervous system alteration in brain processing of sensory stimuli that go beyond nociception, consistent with a central nervous system pathophysiological component in FM.

Several limitations and future directions remain to be addressed in future studies. First, replication of these results with fully independent validation samples is a next step toward translational utility. The validation process is a long, multistudy, and multipublication effort.[9,26] Second, false-negative cases, ie, patients who are erroneously classified as healthy controls using these brain measures, are always a possibility. Importantly, these brain patterns may not capture other sensory/affective/cognitive processes that may also be altered in patients with FM. Third, the brain pattern–symptom severity correlations that we present are preliminary and need replication in multiple samples. Fourth, further studies are needed to test whether our findings generalize to other chronic pain populations or are specific to FM. Last, all participants included in the study were females and therefore the findings cannot be generalized to the population of men with FM, for which future generalization and validation studies are warranted.

Overall, an important open question concerns the extent to which FM and other chronic pain disorders are pathophysiologically distinct or may share certain brain features independent of primary etiology. Testing the generalizability of the brain patterns we identify here may advance our understanding regarding the common and independent central pathophysiology of distinct chronic pain conditions across domains of sensory processing. Thus, the current approach may help in identifying pain endophenotypes across a spectrum of chronic pain conditions and in providing objective guidance for therapeutic interventions on an individualized basis."

canadjineh

New stuff from 2017:
It's a pdf on studies done and their conclusions regarding gluten sensitivity and FM (and some other diseases). Only a couple pages long plus all the references listed (extra page).
https://researchgate.net/profile/Rossella_Talotta/publication/273783874_Algo-dysfunctional_syndromes_A_critical_digest_of_the_recent_literature/links/5810be3c08aee15d4914f66f.pdf

canadjineh

Bump! I'll add more when stuff comes into my inbox but seems like not much happening on the FM front right now in clinical studies etc.

canadjineh

New studies/hypotheses Jan 2018:
Fibromyalgia and unexplained widespread pain: The idiopathic cerebrospinal pressure dysregulation hypothesis

canadjineh

Passive body heating improves sleep patterns in female patients with fibromyalgia
Partial quote:

Reductions in slow wave sleep and increased sleep fragmentation caused by awakenings (5,12) are among the sleep pattern alterations reported by more than 90% of patients with FM (35). Promisingly, an increase in slow wave sleep after treatment with peripheral passive body heating was observed in the present study. Slow wave sleep is considered a facilitator of muscle recovery and a great peripheral restorer, given that growth hormone is primarily released during this sleep stage. This result, combined with the significant reduction in the number of awakenings, suggests that sleep patterns were significantly improved in FM patients following passive body heating therapy. Indeed, less fragmented sleep leads to a more consolidated sleep pattern.

canadjineh

Here's the definitive documents for FM (Canada) - this was set out for doctors by doctors, peer reviewed and has all the symptoms and tests laid out. Link 1 (The main page from the ME/FM Society of BC) https://mefm.bc.ca/single-post/2017/08/01/%E2%80%8BFM-CANADIAN-CONSENSUS-DOCUMENTS
and Link 2 (The actual document itself - 107 pages including references and appendices) mefmaction.com/images/stories/Medical/FMConsensusDocumentbk.pdf

canadjineh

Bump to top of FM forum page

canadjineh

Tai Chi Beats Aerobic Exercise for Fibromyalgia

Compared with aerobic exercise, the traditional martial art of tai chi is as good as, or better than, aerobic exercise, for improving the overall severity of fibromyalgia symptoms, new research shows.

Results of a 52-week single-blind trial showed that in addition to fibromyalgia symptom relief, tai chi was associated greater improvements in depression, anxiety, self-efficacy, and the mental component of the Short-Form Health Survey (SF-36) quality-of-life measure.

"Compared with aerobic exercise, the most commonly prescribed non-drug treatment, tai chi appears as effective as or better for managing fibromyalgia," the investigators, led by Chenchen Wang, MD, Tufts University School of Medicine in Boston, Massachusetts, write. "This mind-body approach may be considered a therapeutic option in the multidisciplinary management of fibromyalgia."

The study was published online March 21 in the BMJ. https://bmj.com/content/360/bmj.k851

Complex Disorder
A complex disorder, fibromyalgia is characterized by chronic widespread musculoskeletal pain, fatigue, sleep disturbance, and prominent physical and

psychological impairment, the investigators note. Estimates suggest it affects 2% to 4% of the general population aged 18 to 65 years.

Aerobic exercise is recommended as a standard treatment for fibromyalgia, but many patients find it difficult to exercise because of fluctuations in symptoms. Some trials have suggested that tai chi alleviates pain and improves physical and mental health in patients with fibromyalgia but concluded that larger and more rigorous trials are needed to confirm the results.

In addition, the duration and frequency of tai chi required to achieve optimal benefit are unknown, as is its efficacy compared with that of aerobic exercise in this patient population.

To find out more, the investigators conducted a prospective, randomized, 52-week, single-blind, comparative effectiveness trial.

The study included 226 people with fibromyalgia who were randomly assigned to receive supervised aerobic exercise for 24 weeks, twice weekly (n = 75), or one of four Yang-style supervised tai chi interventions, 12 or 24 weeks once or twice weekly (n = 151). Participants were followed for 52 weeks. Investigators report adherence was "rigorously" encouraged in person and by telephone.

The study's primary outcome was change in the revised Fibromyalgia Impact Questionnaire (FIQR) scores at 24 weeks compared with baseline. Secondary outcomes included changes of scores in patients' global assessment, anxiety, depression, self-efficacy, coping strategies, physical functional performance, functional limitation, sleep, and health-related quality of life as measured by the Short-Form Health Survey (SF-36).

The mean age of participants was 52 years, 92% were women, the racial/ethnic composition was diverse (61% white), and mean body mass index was 30 kg/m2. The average duration of body pain was 9 years.
Participants had poor health status at enrollment, indicated by an average SF-36 physical score that was about 2 standard deviations below that of the general US population.

Each supervised session lasted 1 hour, and all participants were encouraged to include at least 30 minutes of tai chi or aerobic exercise in their daily routine during the intervention period. The researchers also asked participants to continue their exercise routines for up to the 52-week follow-up.

Research staff blinded to group assignment measured body mass index, treatment expectations, adherence, safety, and physical performance on the 6-minute walk test.

People in the tai chi groups attended 62% of classes vs 40% of participants in the aerobic exercise group.

"Participants assigned to the mind-body therapy maintained higher and more consistent attendance than those assigned to aerobic exercise. Tai chi, which consists of a gentler, low impact meditative sequence of movements with minimal side effects, may be better embraced by patients with fibromyalgia in the long term," the authors write.

FIQR scores improved for participants in all groups compared to baseline at the 12-, 24- and 52-week evaluations. Participants in all five groups demonstrated a similar reduction in use of analgesics, antidepressants, muscle relaxants, and antiepileptic agents over time.

A total of 183 participants (81%) completed the 24-week evaluation. At this time point, improvement in FIQR scores in the combined tai chi groups was significantly greater than in the aerobic exercise group (P = .03).

The duration of tai chi mattered, with people in the 24-week groups reporting greater improvements in FIQR scores compared with those in the 12-week groups. The difference was statically significant (P = .007).

When the investigators looked at the frequency of tai chi, they found no significant difference in effectiveness at 24 weeks between those who participated in tai chi once a week and those participating twice a week, suggesting tai chi once a week may be sufficient to see the reported improvements.

Secondary outcomes at 24 weeks that also significantly favored the tai chi groups included patient global assessment (P = .005), Hospital Anxiety and Depression Scale anxiety scores (P = .006), self-efficacy (P = .004), and coping strategies (P = .005).

A total of 154 adverse events (AEs) were reported in the study. This included 117 AEs among 115 participants assigned to tai chi and 37 among 75 participants in the aerobic exercise group. Most were minor musculoskeletal events, the authors noted, but 8 AEs in the tai chi group and 4 in the aerobic exercise group were considered related to the interventions.

Rethinking the Standard Treatment
"It may be time to rethink what type of exercise is most effective for patients with fibromyalgia," Wang writes in an opinion piece accompanying the study.

"Despite the well-established benefits of aerobic exercise as a core standard treatment for fibromyalgia, patients in our trial had difficulty adhering to the aerobic exercise programme. This may not be surprising — many patients with fibromyalgia find performing and adhering to exercise programs hard. Complaints such as 'the floor is too hard,' 'I cannot stand this,' 'I'm too tired,' or 'I'm in too much pain' were common."

Three instructors taught tai chi in the study. The outcomes were consistent across these instructors, suggesting that the "classic Yang style tai chi can be deployed in other settings in a standardized manner for fibromyalgia," the authors write.

In another accompanying opinion piece, Amy Price, a trauma survivor with chronic pain and a former neurocognitive rehabilitation consultant, notes that her "balance was poor from brain and spinal damage, and I could only see the depressing future of being a patient with chronic pain. I didn't expect tai chi to work, but thought I'd give it a chance."

"Initially, I could only do ten minutes, three times a week, with constant supervision, because of memory and balance problems. Gradually, over about six weeks, my balance improved and this reduced anxiety and increased strength in my broken body," she writes. She would generally recommend tai chi for others with fibromyalgia but recommended patients discuss the option with their physician first, that they stop and speak up if they feel any pain, and that the quality of the instructor matters.

The National Institutes of Health National Center for Complementary and Integrative Health, the National Center for Research Resources, and the National Center for Advancing Translational Sciences funded the study. Wang has disclosed no relevant financial relationships. Price is The BMJ Patient Editor for Research and Evaluation and serves on the BMJ Patient Panel. She has disclosed no relevant financial relationships.

BMJ. Published online March 21, 2018. Abstract

melmerritt33

Interesting, thanks for posting. I’ve wondered about trying this type of exercise again since every other exercise just seems doomed to failure.

canadjineh

I might check into it again too. I used to take one of my rehab physio clients to a class. It helped him a lot with his brain injury recovery.

canadjineh

New studies sent from Journal of Clinical Rheumatology to my inbox via Medscape: Now that recreational cannabis is legal here, it will be easier to get than the old medical cannabis system was. Think I will try it next year with edibles or oils as smoke/vapour in the lungs causes other problems.

Medical Cannabis for the Treatment of Fibromyalgia
George Habib, MD, MPH; Suheil Artul, MD

DISCLOSURES J Clin Rheumatol. 2018;24(5):255-258.

Abstract
Background: Fibromyalgia is a chronic pain syndrome, characterized by chronic musculoskeletal pain, fatigue, and mood disturbances. There are nearly no data on the effect of medical cannabis (MC) treatment on patients with fibromyalgia.

Methods: Data were obtained from the registries of 2 hospitals in Israel (Laniado Hospital and Nazareth Hospital) on patients with a diagnosis of fibromyalgia who were treated with MC. After obtaining patient consent, demographic, clinical, and laboratory parameters were documented. All the patients also completed the Revised Fibromyalgia Impact Questionnaire regarding the period before and after MC treatment.

Results: Thirty patients were identified, and 26 patients were included in the study. There were 19 female patients (73%), and the mean age of the study group was 37.8 ± 7.6 years. The mean dosage of MC was 26 ± 8.3 g per month, and the mean duration of MC use was 10.4 ± 11.3 months. After commencing MC treatment, all the patients reported a significant improvement in every parameter on the questionnaire, and 13 patients (50%) stopped taking any other medications for fibromyalgia. Eight patients (30%) experienced very mild adverse effects.

Conclusions: Medical cannabis treatment had a significant favorable effect on patients with fibromyalgia, with few adverse effects.

Introduction
Fibromyalgia is one of the most common chronic pain syndromes.[1] It is characterized by diffuse musculoskeletal pain, in addition to extreme fatigue and mood and sleep disturbances.[1] The pathogenesis of fibromyalgia is not clear. It usually affects women more than men and has a genetic preponderance.[2] Its prevalence in the general population is estimated to be approximately 7%, and it is more common among women than men.[3]

Fibromyalgia can have tremendous physical, as well as psychological, impacts on patients.[4] For example, many patients may be unable to accomplish various tasks at work and home, resulting in physical disability, which can be accompanied by anxiety and depression. Unfortunately, in most patients, fibromyalgia is chronic, and the main treatment is pain control medications. These medications include simple analgesics, pregabalin, and opiates.[5,6] Patients with fibromyalgia may also benefit from tricyclic antidepressants, benzodiazepines, and other types of antidepressants.[7] However, many of these medications are associated with adverse effects, which affect compliance. As a result, many patients with fibromyalgia experience continuous pain.

Cannabis is derived from the cannabis plant and is considered an illicit drug in most countries, including Israel. However, it is widely used illegally or legally in some countries where cannabis use is not outlawed.[8] The 2 main cannabis plant species are Cannabis sativa and Cannabis indica.[9] Most species today are a hybrid of the two, with cannabis derived from C. sativa designed mainly for morning or daytime use because it induces "energy" and cannabis derived from C. indica reserved primarily for evening or nighttime use because it induces calmness and good sleep.[10] The flowers of the cannabis plant contain more than 100 types of phytocannabinoids. Most research has focused on Δ-9-tetrahydrocannabinol and cannabidiol, both of which have the highest concentrations of phytocannabinoids.[11] There are 2 known receptors of endogenous cannabinoids (endocannabinoids): CB1 and CB2.[12] CB1 is mainly found in the central nervous system.[12] CB2 is found in different organs of the body, with its activities mainly related to the immune system.[12] Δ-9-Tetrahydrocannabinol is a partial agonist for the CB1 and CB2 receptors, and cannabidiol is an antagonist. Activation of CB1 results in a decrease in synaptic signals and neurological excitability.[13]

In recent years, cannabis had been legislated in some states in the United States for medical use, as well as in some countries in Europe.[14,15] In Israel, medical cannabis (MC) is licensed by the Israeli Medical Cannabis Agency of the Ministry of Health for patients with specific indications, including cancer with uncontrolled pain, Crohn disease with uncontrolled gastrointestinal symptoms, uncontrolled seizures, uncontrolled Parkinson disease, posttraumatic stress disorder, and unresponsive diabetic neuropathy. Requests for an MC license are submitted by the specialist taking care of the patient. Based on the recommendations of the Israeli Rheumatology Association, fibromyalgia is not included in the list of indications for MC. However, approval for MC treatment may be granted in some cases of fibromyalgia, especially for fibromyalgia patients who are also receiving treatment by other subspecialties, such as pain clinics, orthopedics (for discopathy), psychiatrists, and/or gastroenterologists (for irritable bowel syndrome). In most cases, following approval, the starting dose of MC is 20 g per month. The drug may be supplied directly to the patient every month or collected from a distribution center. Initially, the patient will be instructed in the use of MC by the supply team, and the patient may choose the mode of consumption (i.e., smoking, vaporization, oral oil drops, or a combination of these). There are 8 suppliers of MC in Israel, and the patient has the right to choose the company that supplies the MC. The patient is advised to consume the same amount of MC daily to prevent a shortage of MC by the end of the month.

There are only a few studies in the literature on the use of cannabis by fibromyalgia patients.[16,17] In these studies, the patients used unlicensed cannabis from different suppliers, and the studies contained no information on either the type or amount (in grams) of cannabis used. In general, the patients in these studies reported favorable effects of cannabis use. A systematic review of the use of synthetic cannabinoids in fibromyalgia (nabilone, 2 studies) found evidence (very low quality) of a greater reduction in pain and limitations in health-related quality of life in the synthetic cannabinoid group as compared with a placebo group in 1 study and better effects of synthetic cannabinoids on sleep than amitriptyline in another study.[18] The aim of the present study was to examine the effects of licensed MC on patients with fibromyalgia in an Israeli population.

Patients and Methods
This was a retrospective review of patients with fibromyalgia who were treated with MC. Data were obtained on patients with fibromyalgia from the registries of Laniado Hospital, Netanya, and Nazareth Hospital, Nazareth, Israel. All the patients met the diagnostic criteria for fibromyalgia.[19] The patients were contacted and asked to participate in the study.

The inclusion criteria were patients older than 18 years and being able to sign a consent form. The exclusion criteria were patients with malignancy-associated or other rheumatic disease–associated fibromyalgia.

All the patients signed a consent form, and the study was approved by the local ethics committee of Laniado Hospital.

After obtaining consent, demographic, clinical, and laboratory parameters were documented. Demographic data included age and sex. Clinical data included the duration of symptoms of fibromyalgia, time of disease diagnosis, medical treatment before and after MC treatment, dose of MC, mode of consumption, adverse effects of MC, employment status, impact of MC treatment on return to work (part-time or full-time work), and number of hours of work. Laboratory parameters included serological markers and vitamin B12 status.

In addition, all the patients completed the Revised Fibromyalgia Impact Questionnaire (FIQR) on the period before and after MC treatment.[20] The patients were asked to document any medical treatment they had received for fibromyalgia in the 2 months prior to starting MC treatment and during the 2 months while receiving MC treatment. Simple analgesics were considered paracetamol, dipyrone, or orphenadrine citrate combined with paracetamol. Mild opiates were considered tablets containing equal to or less than 30 mg of codeine or equal to or less than 100 mg tramadol per day. Strong opiates were considered any treatment containing oxycodone, patches containing fentanyl or buprenorphine, and tablets containing more than 200 mg tramadol per day. The participants were also asked about adverse effects associated with the use of MC. In the questionnaire, all the participants were asked to describe their experience of MC treatment in their own words.

For statistical analysis, Wilcoxon signed rank test was conducted to compare the results of questionnaire data before MC treatment with those after MC treatment. A χ 2 test was performed to compare the number of patients receiving different types of medications prior to MC treatment with the number of patients receiving the same types of medications while receiving MC treatment.

This long 4 page article continued in next post

canadjineh

Medical Cannabis for the Treatment of Fibromyalgia
George Habib, MD, MPH; Suheil Artul, MD

DISCLOSURES J Clin Rheumatol. 2018;24(5):255-258.
cont'd

Results
Thirty patients were identified. One patient could not be contacted. Two patients had cancer, and 1 patient had inflammatory joint disease. Thus, 26 patients were included in the study. Nineteen patients (~73%) were females, and the mean age of the study group was 37.8 ± 7.6 years. The mean duration of a fibromyalgia diagnosis was 4.3 ± 2.64 years. The mean dose of MC was 26 ± 8.3 g per month, and the mean duration of treatment was 10.4 ± 11.3 months, with a median duration of 3 months. No patient ceased MC treatment.

Table 1 summarizes the demographic and clinical parameters of the patients. All the patients smoked or inhaled MC. One of the 26 patients used a combination of smoking and oral oil drops. Table 2 summarizes the mean score for each item in the FIQR before and after MC treatment. Table 3 summarizes the various medications patients took in the 2 months prior to MC treatment and in the 2 months under MC treatment. In the study group, 13 patients (50%) ceased taking any medication other than MC. Twelve patients (~46%) reduced the dose/number of mediations by at least 50% as compared with the dose/number of mediations prior to MC treatment. Table 4 summarizes the adverse effects of MC treatment reported by the patients.
(adverse effects noted in table 4 = dry mouth, red eyes, feeling of hunger)

Discussion
The main finding of the present study was that MC treatment was associated with significant favorable outcomes in every item evaluated in the FIQR. In some cases, the improvement was so marked that the patients completely ceased treatments they had taken previously. In other cases, the patients significantly reduced the dose or type of medication they had taken prior to MC treatment.

The patients expressed the effects of the treatment in their own words, and their responses were dramatic. Very rarely as physicians have we encountered such responses in real-life medicine, except possibly among patients treated with steroids for inflammatory conditions, such as polymyalgia rheumatica or rheumatoid arthritis.

Examples of the patients' responses were as follows: "I wish I had received this treatment when I was first diagnosed with fibromyalgia," "I returned to be the same person as before," "I regained my health," and "This is a miraculous treatment."

For some items of the FIQR, all the patients reported a favorable outcome. These included the effect of MC on pain and energy levels. For other items, the impact was less prominent, yet significant. These included the impact of MC on memory problems and daily activities of living, such as household activities (e.g., cleaning the house and changing bed sheets) and shopping (e.g., carrying grocery bags).

Another major benefit of MC treatment was a lack of serious adverse effects. The patients reported a few mild adverse effects, including dry mouth, redness of the eyes, and feeling hungry. These adverse effects appeared from the start of the treatment. The first 2 adverse effects were usually transient, lasting only a few weeks, and were mainly encountered in cases where the mode of MC was smoking. Many patients adapted to feeling hungry by eating prior to the use of MC.

The mean dose of MC consumed in the present study was relatively low (26 ± 8.2 g per month) as compared with that consumed by patients who receive MC for other indications, such as cancer pain. In the latter case, the dosage exceeded 60 g per month (personal communication, Dr. Salem Billan, oncologist, Rambam Medical Center, Haifa, oral communication, on July 1, 2017). In the present study, many patients continued to take 30 or even 20 g per month, which were the lowest starting doses, suggesting that consumption of approximately 1 g or less a day could be sufficient to control most symptoms of fibromyalgia. The findings of the present study should reassure health policy makers and health care providers that most fibromyalgia patients will remain on a relatively low dose.

There are no studies on tolerance among MC users. However, a previous study of other recreational cannabis users found no tolerance to subjective effects of cannabis.[21]

In the current study, 12 patients (46%) reported either an improvement in their capacity to work or return to full-time work (data not shown). The aforementioned finding has implications for the patient, the patient's family, and society. A literature search revealed no studies on this issue of return to work, among patients treated with MC for different indications. However, a large study of the impact of illicit use of cannabis reported detrimental effects on employment and labor force.[22]

Although previous research proposed a role for endocannabinoid deficiency in fibromyalgia,[23] the potential role of endogenous cannabinoids in the pathogenesis of fibromyalgia remains unclear. More studies are needed to clarify their role. The distribution of cannabinoid receptors in the body may favor the proposed theory of central sensitization in the pathogenesis of fibromyalgia.

The long-term effects of MC treatment remain unclear. All MC request forms submitted to the Israeli Medical Cannabis Agency of the Ministry of Health that are signed by all patients clearly state that the long-term effects of MC are not known. Previous studies showed gray matter volume reductions in different parts of the cortex and functional impairments in various cognitive skills among cannabis users.[24,25] However, these studies involved individuals with heavy cannabis use and not patients under licensed MC treatment who received much lower doses.

Given the somewhat arbitrary selection of patients by the Israeli Medical Cannabis Agency to receive MC for their fibromyalgia, we do not know if the conclusions of our study could be generalized to all fibromyalgia patients, mainly those with severe pain. However, the consistent findings of the impact of MC on many of the FIQR items, especially on pain, allude to the validity of the results.

The main drawback of the present study was its retrospective nature, where patients were asked to answer questions regarding the period prior to their use of MC. However, most patients (~54%) answered the questionnaire a relatively short period after starting MC treatment (i.e., ≤3 months) Second, as mentioned earlier, fibromyalgia is not among the indications for MC treatment. Based on personal experience, fewer than 5% of requests for MC treatment for fibromyalgia are approved. Thus, it seemed unpractical to administer the questionnaire a priori to all patients with fibromyalgia whose doctor submitted a form for MC licensing.

Disclosures:
George Habib, MD, MPH*†‡ and Suheil Artul, MD§||

*Rheumatology Unit, Laniado Hospital, Netanya; †Faculty of Medicine, Technion, Israel Institute of Technology, Haifa; ‡Rheumatolgy Clinic and §Department of Radiology, Nazareth Hospital, Nazareth Hospital, Nazareth; and ||Galilee Faculty of Medicine, Bar Ilan University, Ramat Gan, Israel.

Correspondence
George Habib, MD, MPH, Rheumatology Unit, Laniado Hospital, Netanya, Israel 42150. E–mail: gshabib@gmail.com.

The authors declare no conflict of interest.

canadjineh

New Gastroenterology article in Medscape Apr 22/2019

The Overlap of Irritable Bowel Syndrome and Noncoeliac Gluten Sensitivity
Anupam Rej; David S. Sanders

Curr Opin Gastroenterol. 2019;35(3):199-205.
DISCLOSURES:
Anupam Reja - a, and David S. Sanders - a,b

a-Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust and b-Academic Unit of Gastroenterology, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
There are no conflicts of interest.
Abstract and Introduction
Abstract
Purpose of review: There has been significant interest in gluten over the last decade, with an increase in interest of gluten-related disorders outside coeliac disease. Particularly, there has been a focus on the role of gluten in noncoeliac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS). There is significant overlap between both of these conditions, with the aim of this review to explore their complex relationship.

Recent findings: Gluten has been demonstrated to generate symptoms in individuals with NCGS. However, there appears to be an increasing role for gluten in symptom generation in patients with IBS also. Other components of wheat, other than gluten, are now also thought to be contributing factors in symptom generation.

Summary: There appears to be significant overlap between IBS and NCGS. It is likely that a subset of patients presenting with IBS actually have NCGS. In addition, it is likely that individuals with IBS may also have symptoms triggered by gluten. With the pathophysiology of both conditions not fully understood, as well as increasing knowledge of wheat components in symptom generation, further research is required to help distinguish between both.

Introduction
There has been a significant increase in the interest in gluten over the last decade, with over $15 billion spent in the gluten-free industry in the United States alone in 2016.[1] Many individuals report wheat sensitivity, having been reported as 10%.[2] However, only 1% of individuals have coeliac disease.[3] This has led to an interest in gluten-related disorders outside the diagnosis of coeliac disease, with a recent focus on noncoeliac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS).

NCGS is a condition first described in the late 1970s.[4] It is characterized by the development of intestinal and extraintestinal symptoms following the ingestion of gluten, provided that coeliac disease and IgE-mediated wheat allergy have been excluded. IBS presents with symptoms similar to NCGS, including abdominal pain, bloating and change in bowel habit.[5]

Whilst gluten has been noted to trigger symptoms in individuals with IBS and NCGS, it is now understood that other components in wheat may also trigger symptoms. These include amylase trypsin inhibitors (ATIs), wheat germ agglutenins (WGAs) and fermentable oligosaccharides, disaccharides , monosaccharides and polyols (FODMAPs).[6] With a lack of biomarkers for NCGS and a similar presentation to IBS, this has made it challenging to distinguish between these two clinical entities. This aim of this review is to explore the overlap between both of these conditions.

Whilst the pathophysiology of NCGS is not fully understood, it has been hypothesized that individuals with NCGS may have non-IgE-mediated wheat allergy.[18] In a large study by Carroccio et al.,[16] it was noted that the majority of individuals with wheat sensitivity were demonstrated to be suffering from cow's milk protein sensitivity. This condition is well known in the paediatric population, and could potentially suggest a non-IgE-mediated food hypersensitivity.[18] Also, a higher frequency of food allergy in the paediatric age was noted in the study, which would support this hypothesis.[18]
Elevated levels of fatty acid-binding 2 protein, a marker of intestinal epithelial cell damage, have been demonstrated to be elevated in patients with NCGS, also supporting the hypothesis of compromised intestinal epithelial barrier integrity.[20]

Gluten has been demonstrated to effect bowel barrier function in patients with IBS. A randomized controlled trial (RCT)[23] in 45 patients with IBS-D involved a 4-week trial of either a gluten-free diet (GFD) or gluten-containing diet (GCD). Small bowel permeability was demonstrated to be higher on a GCD, which was greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients. Expression of tight junction proteins (ZO-1, occludin and claudin-1) were demonstrated to be lower on a GCD. Another study[24] also demonstrated changes in tight junction proteins following gluten in IBS. This study demonstrated alterations in myosin light chain phosphorylation and claudin-15 and claudin-2 expression with gluten. These findings could potentially explain the changes in intestinal permeability seen in patients with IBS following gluten challenge.[24]

Interestingly, in 36 patients with IBS and suspected food intolerance, confocal laser endomicroscopy (CLE) has shown immediate and dramatic mucosal responses to several antigens. Mucosal responses to antigens were seen in 22 of the 36 patients, including wheat (n = 13). Intraepithelial lymphocytes increased, epithelial leaks/gaps formed and intervillous spaces widened in individuals who had mucosal responses to antigens.[25] This interesting method may help to identify individuals with IBS who have food sensitivity.

Wheat Components Other Than Gluten
The wheat grain has been demonstrated by proteomic analysis to contain several individual components. Wheat grains constitute about 10–12% of protein, of which 80% is gluten.[26] Whilst there has been a focus on gluten leading to the induction of symptoms in NCGS and IBS, several other components of wheat have been implicated as a causal factor, including amylase/trypsin inhibitors (ATIs), wheat germ agglutinins (WGAs) and fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs).[6]

Wheat ATIs represent a family of up to 17 proteins[27] and represent around 4% of the total wheat proteins.[28] ATIs are associated with baker's asthma,[29] and have been suggested as an aetiological mechanism in NCGS by activation of the innate immune system. Wheat ATIs have been demonstrated to drive intestinal inflammation via the activation of toll-like receptor 4, in vitro and in vivo.[30] The activation of toll-like receptor 4 is thought to lead to the upregulation of maturation markers and release of pro-inflammatory cytokines, leading to an innate immune response.[27] It is also thought that modern hexaploid wheat contains higher ATI activity than older variants.[27]

Lectins are generally regarded as antinutrients within food, with WGA being the best studied serial grain lectin. WGAs have been demonstrated to induce an inflammatory response by immune cells.[31] They have been demonstrated to affect enterocyte permeability, which could lead to the translocation of microbial and dietary antigens interacting with the cells of the immune system.[31] It is important to note, however, that human data demonstrating the effect of WGA on inflammatory markers is lacking.[31]

Fructans, which are part of the FODMAP family, are the major short-chain carbohydrates present in wheat-based grains. FODMAPs may lead to the initiation of symptoms in patients with NCGS and IBS. They are short-chain carbohydrates, which are poorly absorbed, leading to an increase in small bowel water content and intestinal transit.[32] They are subsequently fermented in the large bowel, leading to intestinal gas production and distension, which may lead to symptom generation in individuals.[33] Interestingly, similar physiological responses have been noted in healthy individuals as well as those with IBS.

Whilst the Salerno experts' criteria have enabled NCGS to be formally diagnosed, this may not be practical to implement in clinical practice. Many individuals who note that gluten causes symptoms are unlikely to undergo a gluten challenge. Also, issues remain with diagnosis, as several different study designs are used, as well as individuals having an anticipatory nocebo response, which may affect the reported prevalence. Further research is required to understand the pathophysiological basis of NCGS and identification of biomarkers to help aid diagnosis and distinguish between IBS.

There is now emerging evidence that individuals with IBS also may have sensitivity to gluten, with evidence to support a GFD in these patients. A RCT in 45 patients with IBS-D,[23] where patients were placed on a 4-week GFD or GCD, demonstrated an increased number of bowel movements per day on a GCD versus GFD (P = 0.04). A prospective study in 41 patients with IBS-D,[39] evaluating a 6-week GFD demonstrated a reduction in IBS Symptom Severity Score (IBS-SSS) from 286 to 131 on a GFD (P < 0.001). There have been several trials evaluating gluten in IBS and NCGS, as seen in Table 1.

A double-blind crossover trial in 59 individuals with self-reported NCGS,[40] noted a significant increase in gastrointestinal symptom rating scale (GSRS) score in those consuming fructans versus gluten (P = 0.049). This may suggest that fructans is the causal agent for symptoms rather than gluten. However, it has also been highlighted in the literature[5] that FODMAPs as a whole are unlikely to be purely responsible for symptoms experienced by NCGS patients, as individuals improve on a GFD, despite receiving FODMAPs from other sources outside wheat, such as legumes. Also, extraintestinal manifestations of NCGS cannot be explained by the mechanism of action of FODMAPs.

Conclusion
There appears to be significant overlap between NCGS and IBS. It is likely that a subset of patients presenting with IBS symptoms actually have NCGS, best diagnosed currently using the Salerno experts' criteria, although not without its limitations. Whilst individuals with NCGS note that gluten induces symptoms in comparison to IBS, it appears that individuals with IBS may benefit from a GFD also. There is currently debate with regards to the component of wheat is responsible for symptom generation, with further research required to delineate the pathophysiology of both NCGS and IBS. The development of accurate biomarkers in the future may help delineate NCGS and IBS further.

canadjineh

The above article is posted because Fibromyalgia and IBS, NCGS, and Celiac disease are all linked.

melmerritt33

Thanks for that post, very informative. This could explain why I have such a problem with my digestion and in particular when I go off plan and eat bread. I’ve never been properly diagnosed on that side because one of the things they want to eliminate before diagnosing it as IBS or another issue is Coeliac disease and I refuse to eat wheat heavy meals for six weeks solid just to do the test! Just the thought of the discomfort and unpleasantness that would involve puts me off.

canadjineh

Sorry that last post was soooo long and heavy-duty, but it was 6 pages on Medscape. I didn't copy the actual tests set-up and a couple other intro comments because.... too much stuff!

canadjineh

Sorry in advance... a bit heavy on the sci/tech lingo. Full 5 page article is in the September 2019 - Volume 160 - Issue 9 of PAIN - The Journal for the International Association for the Study of Pain or if you have a free Medscape account you can access it here: https://www.medscape.com/viewarticle/917321_1 Title: Virtual Reality, Music, and Pain: Developing the Premise for an Interdisciplinary Approach to Pain Management

Music and Pain
Music-based therapies have been used to mitigate acute[34] and chronic pain[9] as observed using subjective measures (eg, pain rating scales) and objective methods (eg, fMRI).[13]

Neurobiological Bases of Music and Their Relationship With Pain
Several studies have sought to explain the neural underpinnings of the human experience of music in general.[47] Neural responses to music are centered in the nucleus accumbens, a major reward brain center, and its dopaminergic stimulator, the ventral tegmental area.[60,71,72] The activation of the mesolimbic reward system and the release of dopamine in response to music has demonstrated its pleasure-giving capability.[45,46] This highlights the unique ability of music to connect and engage with multiple parts of the brain and music-evoked emotions.[45] Reybrouck et al. compiled results from 12 studies that used network science algorithms. They concluded that music activates the auditory cortex, the brain reward system, and areas associated with the mind wandering, with distinct changes associated with perceptual, action-related, cognitive, affective, and evaluative processes.[70] Studies have also shown that this pathway of anatomical substrates is shared with the perception of pain, indicating that the 2 may be more closely linked than once believed.[48]

The quantitative understanding of MT (Music Therapy) treatments as they relate with pain has also been explored. Dobek et al.[12] used fMRI to examine neural activity related to painful stimuli in subjects listening to music they enjoyed vs controls who had no music, finding altered neural patterns indicative of decreased pain when music was playing. Garza-Villarreal et al. found that listening to music reduced pain in fibromyalgia through top-down regulation of the modulatory network, with higher connectivity between the left angular gyrus, the right dorsolateral prefrontal cortex and the left caudate (lCau), and decreased connectivity with the right anterior cingulate cortex, the right supplementary motor area, and the precuneus and right precentral gyrus. Pain reduction levels were correlated with the connectivity of the left angular gyrus to the right precentral gyrus.[17] If these results are further confirmed, listening to music to activate the pain modulatory systems could open up new strategies for nonpharmacological treatments of pain.

canadjineh

Just bumping to keep this thread in view....unfortunately there is nothing new in the FM field as all eyes are on Covid-19/SARS-CoV-2 these days.

canadjineh

Looking back through my Medscape emails, seems I missed posting this one when it came in. It figures, considering the title and contents. Very apt.
https://medscape.com/viewarticle/904827?src=wnl_edit_tpal&uac=93466FZ&impID=1799911&faf=1

Researchers have reported for the first time that they have found inflammation in the brains of patients with fibromyalgia.

Daniel S. Albrecht, PhD, a postdoctoral fellow with the Department of Radiology at Massachusetts General Hospital, and Harvard Medical School, Boston, and colleagues, joined with a research team led by Anton Forsberg, PhD, of the Department of Clinical Neuroscience at the Karolinska Institute in Stockholm, Sweden, to broaden generalizability and boost statistical power of the study.

The researchers write that although there has been mounting evidence that brain inflammation plays some role in fibromyalgia, this research is the first to show direct evidence of brain glial activation in the poorly understood and difficult-to-treat chronic condition.

The findings were published online September 14 in Brain, Behavior, and Immunity.

In a news release, study coauthor Marco Loggia, PhD, from the Martinos Center for Biomedical Imaging, Massachusetts General Hospital, explains, "The activation of glial cells we observed in our studies releases inflammatory mediators that are thought to sensitize pain pathways and contribute to symptoms such as fatigue."

The evidence may open the door to new treatments and give comfort to those who have been told their symptoms are psychological.

"We don't have good treatment options for fibromyalgia, so identifying a potential treatment target could lead to the development of innovative, more effective therapies. And finding objective neurochemical changes in the brains of patients with fibromyalgia should help reduce the persistent stigma that many patients face, often being told their symptoms are imaginary and there's nothing really wrong with them."

A group of 31 patients who met the American College of Rheumatology definition for fibromyalgia diagnosis (29 women, average age 50.7 ± 11 years old) and 27 healthy controls (25 women, average age 49.4 ± 11 years old) received a hybrid magnetic resonance/positron-emission tomography (MR/PET) brain scan. The study excluded patients with fibromyalgia if they had any pain conditions other than fibromyalgia.

Using the imaging results, researchers found higher levels of the glial marker TSPO, a translocator protein, in several regions of the brain in patients with fibromyalgia relative to healthy controls. They also found that the degree of glial activation was related to the degree of fatigue the patients reported.

"Overall, our data support glial modulation as a potential therapeutic strategy," the authors write.

Fibromyalgia affects about 4 million US adults, according to the Centers for Disease Control and Prevention.

The study was supported by the International Association for the Study of Pain, Martinos Center Pilot Grant for Postdoctoral Fellows, and Harvard Catalyst Advance Imaging Pilot. The Swedish part of the study received funding from Stockholm County Council, Swedish Research Council, Swedish Rheumatism Association, and Fibromyalgiförbundet. The study was also funded by the European Union Seventh Framework Programme and a donation from the Lundblad family. The authors have disclosed no relevant financial relationships.

Brain Behav Immun. Published online September 14, 2018.