Evidence for Inflammation in the Fibromyalgia Syndrome

Despite the traditional non-inflammatory view of the fibromyalgia syndrome [FMS], there is growing evidence for a form of inflammation in FMS. The majority of the evidence for such an assertion comes from studies of abnormal cytokine levels in the serum or in vitro cultures of leukocytes from patients with FMS compared with samples taken from healthy normal controls (1–9). This topic was recently reviewed (10).

Classically, cytokines can be viewed as target specific, non-antibody, peptide/proteins released by activated inflammatory cells and serving as intercellular mediators of inflammation. They represent a form of facilitory or inhibitory communication between cells. The most obvious players in this game of immunological tag are the cytokine-secreting cells, the cytokines and the target cells bearing receptors for specific cytokines. Less intuitive are a class of molecules that can specifically bind to the cytokines and prevent their binding to the target cell receptor. These molecules include soluble cytokine receptor molecules, which presumably have broken free from the surface of target cells. However, another way by which this can be accomplished is with immunoglobulin antibodies that are specific for the given cytokine. The effectiveness of each cytokine in properly influencing the target cell depends on many factors, including the strategic timing of the cytokine's release, the cytokine's ability to alude inactivation or destruction, the avidity of any soluble inactivating agents, the cytokine's concentration in the region of the target cell, the cytokine's half-life in solution, the proximity of the secreting cell to the target cell and the receptiveness of the target cell to the cytokine's message.

To date, most of our information about this process has come from the study of cytokine concentrations in biological fluids with access to the target cells. As we gain experience with these biological systems, it will be increasingly possible to predict the target cell's response based on triangulation of limited information, not unlike the identification of a geographic location based on three points of reference in a global-positioning system.

The lead article for this issue of the Journal of Musculoskeletal Pain [JMP] comes from Delhi, India (11). The authors used the 2010 American College of Rheumatology Fibromyalgia Diagnostic Criteria [2010 ACR FDC] to confirm the diagnosis of FMS (12). Then they used standard technology to measure the plasma concentrations of four cytokines in the interleukin [IL] class; IL-2, IL-4, IL-6 and IL-10. They also documented the plasma concentration of interferon-γ. The Pearson correlation matrix was used to seek relationships between each of the cytokine concentrations and the severity of the study subject's subjective pain. The reader is advised to seek out the authors' findings and interpretations. Be prepared for dramatic findings and surprising implications. Suffice it to suggest that the findings of this study could substantially change our perception of FMS pathogenesis in an important subset of patients. It would appear that one of the triangulation links is revealed for FMS pain and we impatiently await the appearance of others.

The second research contribution to this issue comes from Rize, Turkey (13). The authors proposed to evaluate the relationship between FMS clinical manifestations and those of patients with neuropathic pain. It is interesting to note that what appears to be underlying the central sensitization of FMS is a central neuropathic process while the contemporary definition of neuropathic pain focuses on dysfunction of peripheral neurons. The authors identified 173 female FMS patients and evaluated their painful symptoms by standard FMS criteria and by criteria typically used to assess neuropathic pain. The latter approach identified about half of the FMS patients as exhibiting pain descriptions usually associated with neuropathic pain. Is this an indication that FMS overlaps with neuropathic pain or that some patients have both central and peripheral nervous system involvement? Perhaps, another explanation is that the signs and symptoms of neuropathic pain are not as specific for the usual neuropathic conditions as some would wish to believe. It might be strategic to include FMS as a disease control in studies intending to develop diagnostic criteria for neuropathic pain. The authors offer their views on the relevance of these findings to contemporary views of FMS and neuropathic pain.

A study reported from Kahramanmaras and Bursa, Turkey, was designed as a follow-up to confirm the investigators own earlier observations on dyscognition in FMS (14). The topic of cognitive impairment in FMS was discussed in an earlier JMP editorial (15). The authors' preferred method for the assessment of dyscognition in FMS was the clock drawing test [CDT], which they describe in refreshing detail. The CDT is an interesting method that uses a circle to represent a clock face. The study subject's task with this image is to properly place the missing 12 numbers and to place the hands where they can indicate a specific time of day. A clinician blinded to the participant's study group interpreted the CDT forms and calculated the resultant CDT scores. Three methods were used to score the instrument and the scoring method mattered. A cognitive deficit was documented in FMS when compared with the matched controls. The relationships of that deficit to other comorbid manifestations was well documented. The authors' discussion helps put this issue into perspective despite controversy in the literature resulting from apparently conflicting findings from different studies.

From San Diego, California, United States, has come a report regarding the application of the goodness-of-fit hypothesis to coping strategies in women with FMS (16). One goal was to determine whether goodness of fit would explain the development of depression and mood disturbance in FMS. An additional goal was to determine whether the hypothesis applies to meaning-focused coping in FMS. These approaches have not previously been applied to chronic medical conditions, but FMS was chosen for study because many patients with FMS must find ways of coping despite feelings of distress and lack of control. The participants were 478 women with FMS, who reported having a physician's diagnosis of FMS but that diagnosis was also confirmed by the investigatory team using the 1990 American College of Rheumatology Research Classification Criteria [1990 ACR RCC] for FMS. In general, the authors found that successful coping improves both depression and mood disturbance. The reader is encouraged to carefully review the article for an understanding of the instruments used and how their findings were interpreted. The authors found that the goodness-of-fit hypothesis seems to apply to coping strategies of women with FMS, particularly to those with the highest levels of problem-focused coping. The reader will wish to compare that with the authors' findings with meaning-focused coping. The authors view this kind of study as a fruitful direction for investigators hoping to develop new interventions for people with FMS.

Continuing with the topic of coping, investigators from Porto Alegre, Rio Grande do Sul, Brazil, reported their experience with a case-controlled assessment of religious spiritual coping in FMS (17). Forty-two adult females with FMS recruited from a rheumatology clinic were compared in a cross-sectional case–control design with 90 pain-free females recruited from a gynecology clinic of the same institution. The assessment of religious spiritual coping was accomplished with the validated self-report Brazilian version of a previously developed Religious Spiritual Coping Questionnaire. This questionnaire has the potential to discriminate forms of religious/spiritual coping, both in its positive and negative [the latter, as when the coping strategy is maladaptive] aspects. The results are interesting and worth careful review. The author's parting comment was that “chronic pain may lead to a more a pragmatic approach to struggling against disease.”

Finally, an epidemiology study comes from Kerman, Iran (18). In this study, work-related musculoskeletal pain problems experienced by 110 practicing dentists in the Kerman community were compared with those of a demographically matched cohort of office workers. The evaluating instrument was a self-report questionnaire, which assessed the painful symptoms with respect to their body locations, their duration, their influence on function, and whether medical care had been sought in their regard. The results showed that musculoskeletal problems were common among Iranian dentists despite their relatively short work days, averaging less than 6 h/day. The reader may wonder about the effects of demographic factors and physical exercise on the prevalence of the symptoms. The authors present and discuss those findings.

This issue of the JMP is also favored by having an interesting case report with supportive reviews. From Wolverhampton and Hereford, United Kingdom, a 35-year-old male carried a presumptive diagnosis of FMS but was found to have multiple bony hemangiomatosis (19).

A very interesting paper is included in the Ideas section of this issue (20). The authors' offer a diaphragmatic breathing exercise regimen that could have its effects in central nervous system retraining. The approach could represent a non-invasive and very inexpensive complementary therapy for people with FMS.

Please note the special interest columns which provide reviews of papers published in other medical journals since the previous issue of the JMP. The topics of these reviews are FMS, myofascial pain syndrome and other soft tissue pain syndromes.

See also a review (21) of a new book entitled MRI for Orthopedic Surgeons.

As always, readers of the JMP are invited to submit the original manuscripts for blinded peer review, case reports of general interest, research ideas to promote further investigation and letters to keep us all informed. The JMP editorial office frequently receives relevant books to be evaluated by and for the benefit of our readers. Book reviewers are allowed keep the featured book after the evaluation report is completed. Readers who would be interested in being a book reviewer for the JMP, please communicate that to the editor [[email protected]]. Indeed, there is a good example of such a review in this issue.

Potential authors of contributions to the JMP should note that submissions and all communications between the authors and the JMP staff are to be accomplished online. Visit http://mc.manuscriptcentral.com/wjmp for more details.

The clear mandate of the International MYOPAIN Society [IMS], for which the JMP is the official journal, is to perpetuate the international meeting that has been held every 3 years, but is moving soon to an every 2 years schedule. The next International MYOPAIN Meeting will be MYOPAIN 2013 which will be held in the beautiful Pacific seacoast town of Seattle, Washington, United States. Two years later, the International MYOPAIN 2015 Meeting will be held on an elegant Pacific coast town of Sydney, Australia, as the IMS responds to the goal of better serving our growing numbers of members from Asia and the Pacific Rim. The IMS website www.myopain.com will offer details as they become available.

Be aware that Regional IMS Chapters are beginning to form. The first Regional IMS Chapter to be officially organized was in Thailand. Congratulations to them! The mastermind of that project was Pradit Prateepavanich, MD, PhD, whose contact information is Department of Rehabilitation Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand, EML: [email protected], [email protected], in case others wish to learn how he did it.

Barbara Runnels, MEd, has now officially retired from her post as administrator of the IMS after 16 years of distinguished service. In that capacity, she and her staff shepherded the International MYOPAIN meetings in Chieti, Italy, 1998; Portland, Oregon, United States, 2001; Munich, Germany, 2004; Washington, DC, United States, 2007; and Toledo, Spain, 2010. In addition, she scrimped and saved to build the trust fund to a level that will help ensure that the IMS can survive. Thank you Barbara for your efforts.

The new IMS administrator is Larry E. Bodkin, Jr., M.S., CAE, Executive Director, International MYOPAIN Society, 1876-B Eider Court, Tallahassee, Florida 32308, United States; Phone [phone], Fax [phone]; E-Mail [email protected]; Website www.myopain.org . He is responsible for the new look of the IMS website. Dues payment should be sent to his office. All communications regarding IMS should be directed to him and his staff. As Mr. Bodkin gets things organized in his town of Tallahassee, Florida, United States, we expect great things ahead. Welcome to the IMS team, Larry!