RATIONALE, AIMS AND OBJECTIVES:The primary purpose of this study was to test both classic and novel FM pain and non-pain symptoms to determine their practical efficacy in aiding clinicians to distinguish FM pain from other chronic pain disorders.METHODS:158 pain patients from two primary care clinics were evaluated with history, physical exam, chart review, and a questionnaire containing 26 exploratory symptoms (10 from the Symptom Impact Questionnaire (SIQR) and 16 from the FM literature)). The symptoms were rated on a 0-10 VAS for severity by those patients reporting pain over the past week. Somers' D and mean severity differences between FM and chronic pain patients without FM were used to rank the discriminatory and diagnostic contributions of symptoms.RESULTS:Fifty patients (14.2%) carried a chart diagnosis of FM, 108 (30.7%) had pain but not FM, and 192 (54.5%) who had neither pain nor FM. Comparing means between the two pain groups, the 5 best differentiating symptoms (all, P < .0001) were: a persistent deep aching over most of my body, poor balance (7.4 vs 3.1), environmental sensitivity (6.8 vs 3.0), tenderness to touch (6.8 vs 3.6) and pain after exercise (8.1 vs 4.1). Notably, VAS pain though significantly higher for FM was least discriminatory (6.5 vs 5.1, P < .001). The five best symptoms generated a ROC = 0.85 and Somers' D = 0.69, an accuracy of 81%, and an odd's ratio of 14.4.CONCLUSIONS:Our results herein suggest that clinicians may be well-served to consider symptoms in addition to those contained in current diagnostic criteria when recognizing FM in their chronic pain patients.

Objective. The Symptom Impact Questionnaire (SIQR), now used for over a decade, has strong psychometric properties based on patients' subjective questionnaire data and correlations with other general measures of severity. However, the construct validity of the SIQR in assessing the central features of fibromyalgia (FM) has not been tested specifically with more objective measures. This study examined the construct validity of the SIQR using clinical examination of prominent features of FM, as well as patient questionnaire data. Methods. We determined if SIQR severity groups (low, moderate, high severity) in 158 chronic pain patients (50 FM, 108 Pain/No FM) predicted four central features of FM tenderness and pain: digital palpation tenderness, blood pressure cuff evoked pain, widespread pain locations, and a persistent deep ache question. Results. Low, moderate, and high SIQR severity groups showed concomitant increases in tenderness in response to digital evoked palpation (F= 23.5; p<0.0000; eta(2)(p)=0.23; MR=.54), blood pressure cuff evoked pain (F= 17.0; p<0.0000; eta(2)(p)=0.18; MR=0.48) and number of pain location (F= 38.8; p<0.0000; eta(2)(p)=0.33; MR. 59). Strongest differences in SIQR severity were found in response to the question, "I have a persistent deep aching over most of my body" (F=87.5; p<0.0000; eta(2)(p)=0.53; MR=0.74). Conclusion. The SIQR strongly predicts the central features of FM tenderness and pain including its widespreadness and its multifaceted character. We propose that tenderness, both locally and over most of the body, attendant to the SIQR is the hallmark of the FM phenotype: tenderness is focal, diffuse, deep, and superficial.

The concept of secondary fibromyalgia (FM) has garnered increasing interest over the last decade. This has resulted from the realization that many common rheumatic disorders have an FM comorbidity that influences, or should influence, optimal management1,2. In this edition of The Journal , Wolfe and colleagues reconsider the issue of primary and secondary FM, asking whether they are equivalent3. Currently, there is no universally agreed-upon definition. Dr. Kahler Hench, the originator of the term fibromyalgia , provided this definition: "Fibrositis is considered primary when there is no associated underlying disorder and secondary when it occurs in patients with underlying rheumatic or other organic disease"4. The 1990 American College of Rheumatology (ACR) criteria paper noted: "To avoid argument over the existence or nonexistence of 'secondary fibromyalgia,' which is believed by some investigators to be fibromyalgia caused [author's italics] by another condition, we adopted the term secondary-concomitant fibromyalgia [original italics] to indicate fibromyalgia occurring in the presence of another significant rheumatic disorder which may have been caused by or was merely associated with the patient's fibromyalgia"5. In the current paper by Wolfe, et al , the following definition is given: Secondary FM is FM occurring in the presence of another clinically important and dominant medical disorder3. We agree with this simplified definition and note that there is an ever-increasing list of disorders that have been associated with FM [Table 1; plus the same table with references (Supplementary Table 1, available with the online version of this article)]; whether a patient is designated as having primary FM becomes dependent upon a diligent search for all such associated comorbidities. View this table: Table 1. Fibromyalgia comorbidities. … Address correspondence to Dr. R.M. Bennett, 6119 SW California St., Portland, Oregon 97219, USA. E-mail: bennetrob1{at}comcast.net

We thank the Journal of Pain for the opportunity to respond to Dr. Wolfe. 2 Wolfe F: Letter to the editor: Fibromyalgia criteria. J Pain. 2019 Feb 11. pii: S1526-5900(18)30920-9. https://doi.org/10.1016/j.jpain.2019.02.002. [Epub ahead of print] Google Scholar We would like to emphasize several main points in response to Dr. Wolfe.

Lesley M. Arnold,* Robert M. Bennett,y Leslie J. Crofford,z Linda E. Dean,x Daniel J. Clauw,{ Don L. Goldenberg,jj Mary-Ann Fitzcharles,** Eduardo S. Paiva,yy Roland Staud,zz Piercarlo Sarzi-Puttini,xx Dan Buskila,{{ and Gary J. Macfarlanex Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio yDepartment of Medicine, Oregon Health and Science University, Portland, Oregon zDivision of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee xEpidemiology Group and Aberdeen Centre for Arthritis and Musculoskeletal Health, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Scotland, United Kingdom {Departments of Anesthesiology, Medicine (Rheumatology), and Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan jjDepartment of Medicine, Tufts University School of Medicine, Boston, Massachusetts, and Departments of Medicine and Nursing, Oregon Health and Science University, Portland, Oregon Division of Rheumatology, Department of Medicine, McGill University, Montreal, Quebec, Canada yyDivision of Rheumatology, Department of Medicine, Universidade Federal do Parana, Curitiba, Brazil zzDivision of Rheumatology, Department of Medicine, University of Florida, Gainesville, Florida xxDivision of Rheumatology, Department of Medicine, Milan University, Milan, Italy {{Department of Medicine, H. Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel

Background Fibromyalgia (FM) patients have a wide range of symptoms. Objectives Herein we analysed 20 common symptoms to determine those that best discriminate between FM patients and chronic pain patients without FM (Chronic Pain). Methods 352 patients (mean age 50+/16.3 years, 70% female) scheduled for a routine examination in two primary care practices were studied. 50 patients (14.2%) had FM (based on 1990 ACR) and 108 patients (30.7%) had Chronic Pain. All subjects completed a survey of 20 symptoms commonly found in FM patients – 10 were from the Symptom Impact Questionnaire (SIQR). Results Table 1 presents the 20 symptoms ranked by magnitude of Somers’ D. This is a statistic that provides an estimate of predicting a diagnosis of fibromyalgia versus no fibromyalgia (OR: 1.87–8.00; p<0.001). The top 10 symptoms showed strong correlations with diagnosis (D=0.49 to 0.64) and large mean differences between the 2 groups (Means: 2.8–4.3). Notably, there was a 4.3 score difference in Persistent Deep Ache and only a 1.4 difference in SIQR Pain (p<0.001). Using a 4-point criterion as a clinical cut-off (0–10), symptoms best discriminating patients with FM from Chronic Pain were: Persistent Deep Aching (86% vs. 36%), Environmental Sensitivity (82% vs. 38%), Poor Balance (82% vs. 35%), Tenderness to Touch (84% vs. 39%) and Pain after exercise (96% vs. 54%). The symptoms of Pain, Unrefreshing Sleep, Muscle Stiffness and Low Energy were high in both groups, thus they are not good discriminators. Conclusions In this sample from 2 primary care practices, Persistent Deep Aching, Tenderness to Touch, Environmental Sensitivity, Poor Balance and Pain after Exercise were the best discriminators between FM patients and patients with Chronic Pain. Notably: Depression, Headaches, Poor Memory and Irritable Bowel symptoms were weak discriminators; in fact, none of the top 10 discriminators appear in the 2016 Fibromyalgia Diagnostic Criteria. Disclosure of Interest None declared

Objectives: (1) To assess providers’ experience and knowledge of chronic noncancer pain (CNCP) management. (2) To assess providers’ utilization of the Centers for Disease Control and Prevention (CDC) 2016 Guideline for Prescribing Opioids for Chronic Pain. (3) To assess the influence of the 2016 CDC guideline on provider confidence in managing CNCP and adherence to the CDC recommendations.Methods: A cross-sectional, web-based survey conducted with 417 Oregon prescribing providers, divided into three continuing medical education (CME) groups composed of minimal (0-3), moderate (4-10), and high (≥11) hours of training. Results: The three CME groups were associated with increased use of CDC opioid recommended practices (29.4, 34.2, 38.8; p = 0.001; scale 0-50), opioid conversion confidence (5.5, 6.5, 7.4; p < 0.001; scale 0-9), and confidence in pain management (5.5, 5.9, 6.9; p < 0.001, scale 0-9). Slightly more providers utilized CDC recommended practices than did not (57 vs 43 percent). However, CME groups differed substantially in utilization of CDC practices (42 vs 57 vs 72 percent; p < 0.001). Neither providers’ profession (physician vs nurse practitioner [NP]) nor geographic setting (urban vs rural) showed differences in use of recommended practices or general confident in pain management (all p > 0.05); however, physicians were slightly more confident in opioid dose conversion than NPs (6.9 vs 5.9; p < 0. 001, scale 0-9).Conclusions: Higher hours of recent CME positively benefit provider confidence in pain management and utilization of CDC recommended practices. NPs and rural providers were equivalent to their physician and urban counterparts on confidence and adherence to CDC practices, with minor exceptions.

Fibromyalgia (FM) is a common chronic pain disorder that presents diagnostic challenges for clinicians. Several classification, diagnostic and screening criteria have been developed over the years, but there continues to be a need to develop criteria that reflect the current understanding of FM and are practical for use by clinicians and researchers. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration (FDA) and the American Pain Society (APS) initiated the ACTTION-APS Pain Taxonomy (AAPT) to develop a diagnostic system that would be clinically useful and consistent across chronic pain disorders. The AAPT established an international FM working group consisting of clinicians and researchers with expertise in FM to generate core diagnostic criteria for FM and apply the multidimensional diagnostic framework adopted by AAPT to FM. The process for developing the AAPT criteria and dimensions included literature reviews and synthesis, consensus discussions, and analyses of data from large population-based studies conducted in the United Kingdom. The FM working group established a revised diagnosis of FM and identified risk factors, course, prognosis, and pathophysiology of FM. Future studies will assess the criteria for feasibility, reliability, and validity. Revisions of the dimensions will also be required as research advances our understanding of FM. PERSPECTIVE: The ACTTION-APS FM taxonomy provides an evidence-based diagnostic system for FM. The taxonomy includes diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms. This approach might improve the recognition of FM in clinical practice.

ObjectiveTo investigate whether associations between pain and the additional symptoms associated with fibromyalgia are different in persons with chronic widespread pain (CWP) compared to multisite pain (MSP), with or without joint areas.MethodsSix studies were used: 1958 British birth cohort, Epidemiology of Functional Disorders, Kid Low Back Pain, Managing Unexplained Symptoms (Chronic Widespread Pain) in Primary Care: Involving Traditional and Accessible New Approaches, Study of Health and its Management, and Women's Health Study (WHEST; females). MSP was defined as the presence of pain in ≥8 body sites in adults (≥10 sites in children) indicated on 4‐view body manikins, conducted first to include joints (positive joints) and second without (negative joints). The relationship between pain and fatigue, sleep disturbance, somatic symptoms, and mood impairment was assessed using logistic regression. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs).ResultsThere were 34,818 participants across the study populations (adults age range 42–56 years, male 43–51% [excluding WHEST], and CWP prevalence 12–17%). Among those reporting MSP, the proportion reporting CWP ranged between 62% and 76%. Among those reporting the symptoms associated with fibromyalgia, there was an increased likelihood of reporting pain, the magnitude of which was similar regardless of the definition used. For example, within WHEST, reporting moderate/severe fatigue (Chalder fatigue scale 4–11) was associated with a >5‐fold increase in likelihood of reporting pain (CWP OR 5.2 [95% CI 3.9–6.9], MSP–positive joints OR 6.5 [95% CI 5.0–8.6], and MSP–negative joints OR 6.5 [95% CI 4.7–9.0]).ConclusionThis large‐scale study demonstrates that regardless of the pain definition used, the magnitude of association between pain and other associated symptoms of fibromyalgia is similar. This finding supports the continued collection of both when classifying fibromyalgia, but highlights the fact that pain may not require to follow the definition outlined within the 1990 American College of Rheumatology criteria.

Rationale, aims, and objectivesPrimary care providers are increasingly expected to recognize and treat fibromyalgia (FM) without significant interaction with rheumatologists. The purpose of this study was to evaluate the potential usefulness of 3 simple measures (tenderness to digital pressure, BP cuff-evoked pain, and a single patient question) as a screening test for possible FM in a patient with chronic pain. MethodsA total of 352 patients (mean age 5016.3years, 70% female) scheduled for routine examination in 2 primary care practices were studied. They were comprised of 52 patients (14.8%) who carried a chart diagnosis of FM, 108 (30.7%) with chronic pain but not FM, and 192 who had neither pain nor FM (54.5%). Subjects were assessed for tenderness to digital pressure at 10 locations, BP cuff-evoked pain, and a single question, I have a persistent deep aching over most of my body (0-10). ResultsFM patients endorsed the single deep ache question substantially more than those with chronic pain but without FM (7.4 +/- 2.9 vs 3.2 +/- 3.4; P<.0001) and exhibited greater bilateral digital evoked tenderness (6.1 +/- 3.1 vs 2.4 +/- 2.4, P<0.0001), and BP-evoked pressure pain (132.6mmHg +/- 45.5 vs 169.2mmHg +/- 48.0, P<0.0001). However, on multivariate logistic regressions, the BP cuff-evoked pain became non-significant. On further analyses, a useful screening test was provided by: (1) pain on pinching the Achilles tendon at 4kg/pressure over 4seconds, and (2) and positive endorsement of the question I have a persistent deep aching over most of my body. ConclusionThese results suggest that 2 tests, taking less than 1minute, can indicate a probable diagnosis of FM in a chronic pain patient. In the case of a positive screen, a follow-up examination is required for confirmation or refutation.

Patients with functional pain disorders often complain of generalized sensory hypersensitivity, finding sounds, smells, or even everyday light aversive. The neural basis for this aversion is unknown, but it cannot be attributed to a general increase in cortical sensory processing. Here, we quantified the threshold for aversion to light in patients with fibromyalgia, a pain disorder thought to reflect dysregulation of pain-modulating systems in the brain. These individuals expressed discomfort at light levels substantially lower than that of healthy control subjects. Complementary studies in lightly anesthetized rat demonstrated that a subset of identified pain-modulating neurons in the rostral ventromedial medulla unexpectedly responds to light. Approximately half of the pain-facilitating "ON-cells" and pain-inhibiting "OFF-cells" sampled exhibited a change in firing with light exposure, shifting the system to a pronociceptive state with the activation of ON-cells and suppression of OFF-cell firing. The change in neuronal firing did not require a trigeminal or posterior thalamic relay, but it was blocked by the inactivation of the olivary pretectal nucleus. Light exposure also resulted in a measurable but modest decrease in the threshold for heat-evoked paw withdrawal, as would be expected with engagement of this pain-modulating circuitry. These data demonstrate integration of information about light intensity with somatic input at the level of single pain-modulating neurons in the brain stem of the rat under basal conditions. Taken together, our findings in rodents and humans provide a novel mechanism for abnormal photosensitivity and suggest that light has the potential to engage pain-modulating systems such that normally innocuous inputs are perceived as aversive or even painful.

Pain ManagementVol. 6, No. 4 Special Focus Issue: Pain management in fibromyalgia – ForewordFree AccessPain management in fibromyalgiaRobert M BennettRobert M Bennett*Author for correspondence: E-mail Address: bennetrob1@comcast.net Professor of Medicine & Nursing, Oregon Health & Sciences University, Portland, OR 97239, USASearch for more papers by this authorPublished Online:13 Jul 2016https://doi.org/10.2217/pmt-2016-0026AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: fibromyalgiaopioidspainFirst draft submitted: 20 June 2016; Accepted for publication: 20 June 2016; Published online: 13 July 2016Fibromyalgia is a multidimensional pain syndrome that currently defies an exact definition [1]. Nevertheless, rheumatologists, pain specialists and increasingly primary care providers, are gaining confidence in making this diagnosis and initiating treatment [2]. The multidimensionality of fibromyalgia stems from its amalgamation of diverse symptoms: widespread pain, tenderness, fatigue, nonrefreshing sleep, musculoskeletal stiffness, cognitive dysfunction, environmental sensitivity, mood disorders, poor balance, muscle weakness, functional impairments and disability [3]. Moreover, there are the commonly associated issues of irritable bowel syndrome, restless leg syndrome, overactive bladder, pelvic pain, vulvodynia, dyspareunia, migraine headaches, paresthesia and suicidal ideation. Furthermore, the majority of fibromyalgia patients have one or more comorbidities unrelated to fibromyalgia, such as osteoarthritis, rheumatoid arthritis, obesity, low back pain, systemic lupus erythematosus, traumatic injuries and psychological traumas such as post-traumatic stress disorder [4]. Against this backdrop, it is little wonder that clinical research studies, especially those involving medications, usually fail to deliver encouraging results. This is well exemplified by several of the papers in this issue of Pain Management.The problem of multidimensionality in fibromyalgia patients is mentioned by several authors. This is well summed up in Dr Turk's review which noted “despite similarities in symptoms, patients with fibromyalgia are unique, and require individualized treatment based on their symptoms and experiences. Providers must avoid adopting the ‘patient-uniformity myth’, assuming that all patients with the same diagnosis are identical and thereby require the same treatment regimen.” This therapeutic mindset is helped by understanding fibromyalgia from a biopsychosocial perspective. While there is good evidence of central sensitization and defective pain modulation in fibromyalgia patients, it is increasingly apparent that subcortical nociceptive transmission is modified by psychosocial factors [5]. From this perspective, the patient's subjective experience of central sensitization is influenced by psychological variables such as mood states, sociocultural environment, past experiences, its expectancy beliefs, catastrophization and other behavioral factors.Patient education is a key factor in developing a beneficial patient–doctor relationship [6]. Patients have to understand that there is currently no cure for fibromyalgia; searching endlessly for what is ‘medically wrong’ detracts from their engagement and self-management. As Dr Turk notes, “a blind focus on illness per se ignores the real ability of individuals with fibromyalgia to make meaningful gains, and further keeps them from enjoying life that they have before them despite symptoms.” Cognitive–behavioral therapy is currently the favored approach that focuses on thoughts, feelings and behaviors, and is thus ideally suited for treating fibromyalgia from a biopsychosocial perspective. Important components of cognitive–behavioral therapy are as follows [7]:Education reassurance;Focus on functional gains rather than fibromyalgia as a disease;Realistic goal setting;Lifelong self-management;Pacing and increasing activities;Managing sleep;Addressing cognitive dysfunction – use of daily planners, to do lists, attention techniques;Recognizing the role of stress in symptom development;Counteracting maladaptive thinking;Relapse and maintenance;Improved communication with others;Assertiveness training; andUse of medications.Many fibromyalgia patients state that fatigue is their major problem [8]. Our understanding of the neurophysiology fatigue is still in its infancy. Dr Mannerkorpi's special report concludes that fatigue and sleep disturbance are multifactorial, and partly related to hypersensitivity to unpleasant sensory stimuli. She recommends that the management of fatigue needs to incorporate regular physical exercise with appropriate pacing and improved sleep hygiene. However, many patients find that exercise often aggravates their pain and fatigue, and they drop out before any benefits are realized. Keeping patients in an exercise program is the subject of Dr Jones' editorial. She advises to avoid discussing an ‘exercise program’. Rather, the patient needs to focus on increasing physical activity, not necessarily going to the gym, among others. She provides a menu of ten talking points that providers can use to start a conversation about how to successfully increase their level of activity. Each talking point provides a different way of increasing activity. This is another example of learning a self-management skill that needs a paradigm shift from a passive patient role to an active role. Dr Ablin discusses medications, such as modafinil, that may benefit fibromyalgia-related fatigue [9].Fibromyalgia patients often inquire about dietary interventions [10]. The Internet abounds with recommendations, usually focusing on foods that benefit fibromyalgia patients and foods that aggravate fibromyalgia. Most of these recommendations are anecdotal. However, a few well done research studies support the recommendation of avoiding glutamate and aspartate. Dr Holton's special report notes that glutamate is the major excitatory neurotransmitter in the brain and that fibromyalgia patients have higher levels of glutamate in the cerebrospinal fluid. Aspartate activates NMDA receptors; a crucial first step on the road to central sensitization. Dr Holton discusses three studies that demonstrated benefits from the elimination of monosodium glutamate and aspartame.Central sensitization is driven by peripheral pain generators. With this in mind, all fibromyalgia patients should be carefully evaluated for pain generators, which commonly include osteoarthritis, injuries, migraine headaches, temporomandibular joint dysfunction and myofascial pain. Dr Fernández de las Peñas reviews the role of myofascial trigger points as important pain generators in the development of central sensitization. He outlines various strategies for managing myofascial trigger points. This is apparently an underappreciated topic, as none of the other contributors mention myofascial pain.Dr Goldenberg's editorial starts by noting that systematic reviews of pharmacologic intervention in fibromyalgia have been somewhat discouraging. For instance, he reports that most reviews have found little evidence that selective serotonin reuptake inhibitors are efficacious in fibromyalgia, while most have found only modest efficacy for the dual-reuptake inhibitors [2,3]. Duloxetine and milnacipran provided a small incremental benefit over placebo in reducing pain but not in reducing fatigue or improving sleep or quality of life. Most long-term studies have found little change in symptoms over time but significant individual patient variability.He supports Dr Turk’s notion that ‘the patient uniformity myth’ is a significant factor leading to poor results in clinical trials. Dr Goldenberg suggests that patients entering clinical trials should be stratified according to variables such as pre-existing mood disorders, catastrophizing, multiple somatic symptoms, stress levels, poor sleep, obesity, disability, unemployment and inactivity.Dr Choy's Special Report provides an overview of sleep dysfunction in fibromyalgia patients. In the mid-1970s, Drs Moldofsky and Smythe provided polysomnographic evidence of disordered non-rapid eye movement sleep in fibromyalgia and also produced a transient fibromyalgia-like syndrome in healthy volunteers by disrupting their non-rapid eye movement sleep [11]. Since that time other sleep abnormalities have been described, and their role in modulating dysfunctional sensory processing is described by Dr Choy. He notes that epidemiological and experimental studies have indicated that sleep dysfunction may lead to the development of fibromyalgia, and in healthy individuals sleep disruption impairs pain processing with reduction in descending pain modulation [12]. Among currently available pharmacological treatments, he states that amitriptyline and pregabalin can improve sleep quality. Interestingly, there is one study that finds daytime napping is associated with increased severity.Dr Okifuji's review echoes the views of most contributors in saying “fibromyalgia continues to be a very difficult condition to successfully treat. fibromyalgia is by nature a multi-symptom, possibly multimechanistic disorder; thus any single modality that does not cover relevant areas of fibromyalgia would likely fail. The importance of considering individual variations in developing a personalized approach cannot be overstated.” Dr Okifuji is a strong proponent of using psychological/behavioral approaches in the management of fibromyalgia, and stresses the importance of a patient’s active engagement in all therapies. Until a patient becomes fully committed, the chances of success are considerably reduced. The use of motivational enhancement therapy is a relatively new technique that has the potential for improving the patient’s active engagement in therapy [13].Dr Ablin's review provides a thorough commentary of current medications and novel therapies that are currently being evaluated. He notes that “at the current point in time much of the art of treating fibromyalgia remains an exercise of trial and error.” A recent review in Expert Opinion in Pharmacotherapy complements Dr Ablin’s contribution: according to the available evidence, pregabalin, duloxetine and milnacipran should be the drugs of choice for the treatment of this disease, followed by amitriptyline and cyclobenzaprine. Other drugs with at least one positive clinical trial include some selective serotonin reuptake inhibitors, moclobemide, pirlindole, gabapentin, tramadol, tropisetron, sodium oxybate and nabilone. Combination therapy is an option that needs to be more thoroughly investigated in clinical trials [14].The use of opioids nonmalignant states is currently a ‘hot potato’ [15]. Dr Littlejohn's review states that “there is no evidence that pure opioids, such as morphine or oxycodone have any benefit in fibromyalgia. Tramadol has moderate evidence for efficacy, but adverse events and drug cross-reactions limit its use. Low-dose naltrexone targets activated glial cells and has some evidence of benefit.” Dr Littlejohn has found that buprenorphine, a partial µ-opioid agonist action, with κ- and δ-opioid receptor antagonist actions, is useful in selected fibromyalgia patients, particularly where there is comorbid painful osteoarthritis of the hip, knee and back.Financial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.References1 Bennett R, Friend R, Marcus D et al. Criteria for the diagnosis of fibromyalgia: validation of the modified 2010 preliminary ACR criteria and the development of alternative criteria. Arthritis Care Res. 66(9), 1364–1373 (2014).Crossref, Google Scholar2 Arnold LM, Clauw DJ, Dunegan LJ, Turk DC. A framework for fibromyalgia management for primary care providers. Mayo Clin. Proc. 87(5), 488–496 (2012).Crossref, Medline, Google Scholar3 Bennett RM, Jones J, Turk DC, Russell IJ, Matallana L. An internet survey of 2,596 people with fibromyalgia. BMC Musculoskelet. Disord. 8, 27 (2007).Crossref, Medline, Google Scholar4 Rehm SE, Koroschetz J, Gockel U et al. A cross-sectional survey of 3035 patients with fibromyalgia: subgroups of patients with typical comorbidities and sensory symptom profiles. Rheumatology (Oxford) 49(6), 1146–1152 (2010).Crossref, Medline, Google Scholar5 Fomberstein K, Qadri S, Ramani R. Functional MRI and pain. Curr. Opin. 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North Am. 34(2), e1–e23 (2016).Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited ByMetabolomics analysis of plasma samples of patients with fibromyalgia and electromagnetic sensitivity using GC–MS technique19 December 2022 | Scientific Reports, Vol. 12, No. 1Effectiveness of non-pharmacological conservative therapies in adults with fibromyalgia: A systematic review of high-quality clinical trialsJournal of Back and Musculoskeletal Rehabilitation, Vol. 35, No. 1Systematic analysis of the cerebrospinal fluid proteome of fibromyalgia patientsJournal of Proteomics, Vol. 190The management of fibromyalgia from a psychosomatic perspective: an overview6 July 2017 | International Review of Psychiatry, Vol. 29, No. 5Abordaje integrado de la fibromialgiaFMC - Formación Médica Continuada en Atención Primaria, Vol. 24, No. 7Définition et évaluation de la douleurKinésithérapie, la Revue, Vol. 17, No. 186 Vol. 6, No. 4 Follow us on social media for the latest updates Metrics History Published online 13 July 2016 Published in print July 2016 Information© Future Medicine LtdKeywordsfibromyalgiaopioidspainFinancial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Revised recommendations for the management of fibromyalgia have been published by a multinational EULAR working group. Applying these guidelines to clinical practice will require good clinical judgement and flexibility.

To the Editor: We are somewhat baffled by Dr. Wolfe, el al ’s allegation that our editorial critique1 of their recent paper2 is part of an ongoing opposition to the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia. This seems odd, given that we independently validated those criteria3. Indeed, in contradistinction to Dr. Wolfe’s claim, we reviewed that paper and recommended “acceptance with revision.” Notwithstanding these facts, Dr. Wolfe went on to inaccurately criticize our paper’s methodology, and had to retract his mistake in an Erratum published in Arthritis and Rheumatology 4. Our editorial, solicited by the editor, provides constructive comments, and should be viewed in that light. This is the accepted scientific method for the progressive advancement of knowledge5. Our editorial stated that the Polysymptomatic Distress Scale (PSD) relies on the 19-point Widespread Pain Index (WPI) component as its primary assessment of pain. Wolfe, et al retorted that the WPI pain count “is not a primary assessment of pain” and that “we do not want people to use the WPI to measure pain severity.” Was this a misreading of the editorial? We did not say that the WPI is a primary assessment of pain, but that the PSD relies primarily on … Address correspondence to Dr. R. Friend, 2347 NW Overton St., Portland, Oregon 97210, USA. E-mail: ronald.friend{at}stonybrook.edu

OBJECTIVES:Fibromyalgia (FM) is a common pain disorder characterized by nociceptive dysregulation. The basic biology of FM is poorly understood. Herein we have used agnostic gene expression as a potential probe for informing its underlying biology and the development of a proof-of-concept diagnostic gene expression signature.METHODS:We analyzed RNA expression in 70 FM patients and 70 healthy controls. The isolated RNA was amplified and hybridized to Affymetrix® Human Gene 1.1 ST Peg arrays. The data was analyzed using Partek Genomics Suite version 6.6.RESULTS:Fibromyalgia patients exhibited a differential expression of 421 genes (p<0.001), several relevant to pathways for pain processing, such as glutamine/glutamate signaling and axonal development. There was also an upregulation of several inflammatory pathways and downregulation of pathways related to hypersensitivity and allergy. Using rigorous diagnostic modeling strategies, we show "locked" gene signatures discovered on Training and Test cohorts, that have a mean Area Under the Curve (AUC) of 0.81 on randomized, independent external data cohorts. Lastly, we identified a subset of 10 probesets that provided a diagnostic sensitivity for FM of 95% and a specificity of 96%. We also show that the signatures for FM were very specific to FM rather than common FM comorbidities.CONCLUSIONS:These findings provide new insights relevant to the pathogenesis of FM, and provide several testable hypotheses that warrant further exploration and also establish the foundation for a first blood-based molecular signature in FM that needs to be validated in larger cohorts of patients.