Emma Kathryn Guymer

The use of opioids in fibromyalgia

Fibromyalgia syndrome (FMS) is a chronic disorder of widespread pain with high personal and societal burdens. Although targeted pharmacotherapies have become available in recent years, it remains a challenging condition to treat. Despite no randomized controlled trials addressing the short‐ or long‐term use of opioids in FMS, their use remains prevalent. In this article we discuss the role of opioids and other analgesics in the management of FMS, with particular focus on problems associated with their use. We review aspects of the pathophysiology of FMS and consider how specific factors may contribute to the lack of efficacy of opioids in this condition. Finally, we discuss drugs with combined opioid and anti‐opioid action and their roles in FMS. There is insufficient evidence to recommend the routine use of opioids in FMS. As well as having a significant adverse effect profile, their inefficacy may be due to their inability to target the pathophysiologic processes involved in this central sensitization syndrome.

Fibromyalgia Syndrome: Which Antidepressant Drug Should We Choose

Fibromyalgia syndrome [FM] has core clinical features of widespread pain and widespread abnormal tenderness. The specific cause of the altered neurophysiology that underpins these clinical manifestations remains unclear. However, increased sensitisation of neural networks that relates to pain, as well as interacting mechanoreceptors, appear important targets for modulation by pharmacological agents. Further, many FM patients have emotional distress and some are depressed. Antidepressant agents have therapeutic benefits in FM. If depression is present antidepressant drugs will provide typical benefits to mood but not always to other key outcome measures, such as pain or tenderness. Selective serotonin receptor reuptake blockers are not as effective for overall FM improvement as drugs that block both serotonin and norepinephrine in a relatively balanced way. Thus tricyclic antidepressants will improve many important FM outcomes but are effective in only about 40 percent of individuals. Newer agents of this class, such as duloxetine and milnacipran, show improvement in key FM outcomes in about 60 percent of patients. Longer term studies will indicate the durability of these responses and the overall tolerance of the drugs. Any drug therapy will need to be integrated with appropriate education, exercise and attention to psychological modulatory factors to achieve best results.

Clinical characteristics of 150 consecutive fibromyalgia patients attending an Australian public hospital clinic

To describe clinical characteristics of fibromyalgia in an Australian population.

Whiplash: Same Elephant, Different Room

Musculoskeletal injury can cause acute pain and can also trigger chronic pain. The mechanisms resulting in these 2 outcomes are essentially different, with acute pain relating primarily to peripheral nociception and chronic pain relating primarily to central sensitization. Acute musculoskeletal pain usually resolves with time or treatment. Chronic pain, by definition, persists and associates with significant longterm health effects and diminished quality of life (QOL). Despite the importance of this problem, the issues surrounding persisting pain after injury remain controversial1. Aspects of postinjury pain and disability are addressed in this issue of The Journal through followup of persons involved in minor trauma from motor vehicle accidents2. The clinical features of patients with persisting pain after trauma, where the inciting lesion has resolved, are usually distinctive and embody a number of characteristic pain phenotypes. Central sensitization is the most prominent contributing mechanism3. Common examples are fibromyalgia (FM), regional pain syndrome, and complex regional pain syndrome (CRPS)4. These disorders are characterized by widespread or regionalized pain in a distribution that cannot be explained by an abnormality of a specific localized musculoskeletal or neural structure, be it in the periphery or in the spinal area. The pain may be segmental and often accompanied by unpleasant non-neuroanatomical sensory sensations within the same region. There is widespread or regional lowering of pain threshold elicited clinically by the determination of abnormal tenderness on palpation, more prominent in selected areas known as tender points. Muscular tightness, co-contraction, and development of trigger points are common. There is often mild soft tissue swelling and dermatographia, indicative of neurogenic inflammation. In CRPS more prominent vasomotor, sudomotor, muscle, and dystrophic features are present5. In addition to these physical signs, patients complain to a varying degree about sleep disturbance, fatigue, cognitive dysfunction, … Address correspondence to Dr. Littlejohn, Suite H, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, Australia; E-mail: Geoff.littlejohn{at}monash.edu

GILZ: Glitzing up our understanding of the glucocorticoid receptor in psychopathology

Dysfunction of the hypothalamic-pituitary-adrenal axis, particularly the glucocorticoid receptor, is a commonly implicated link between stress and psychopathology. GR abnormalities are frequently reported in depression, and these anomalies must be resolved before depressive symptoms remit. This biological finding is rendered clinically relevant by the knowledge that only select antidepressants alter GR function. The relationship between GR dysfunction and other diseases associated with psychiatric stress, such as post-traumatic stress disorder (PTSD) and fibromyalgia, is also documented. However, as laboratory constraints limit the utility of GR testing, other measures of GR activity, such as levels of GR-induced genes, may have greater clinical value. In this review, glucocorticoid-induced leucine zipper (GILZ), a product of GR-initiated gene transcription, will be discussed in the context of GR dysfunction in psychopathology.

Fibromyalgia: current diagnosis and management

Fibromyalgia is a common disorder occurring in approximately 2–5% of most populations, with female patients outnumbering males by up to nine to one. The two essential components of fibromyalgia, experienced in conjunction, are widespread pain and widespread abnormal bodily tenderness, although other common features of the syndrome include fatigue, muscle stiffness, poor-quality sleep and emotional distress. The clinical features result from complex changes of pain-related neurophysiological function in the brain and spinal cord, particularly through the neurophysiological process of sensitization. Management of fibromyalgia is directed to the inputs to this process, through a combination of education, exercise and psychological strategies. A number of drugs can also target this mechanism. With use of selected combinations of these strategies, the prognosis of fibromyalgia is now much improved.

Fibromyalgia remains a significant burden in rheumatoid arthritis patients in Australia

High rates of fibromyalgia (FM) are reported in rheumatoid arthritis (RA) patients. Advances in RA management have occurred, but information regarding current significance of FM in RA is limited. This investigation estimated the prevalence and health effects of concomitant FM in Australian RA patients.

Modulation of NMDA Receptor Activity in Fibromyalgia

Activation of the N-methyl-d-aspartate receptor (NMDAR) results in increased sensitivity of spinal cord and brain pathways that process sensory information, particularly those which relate to pain. The NMDAR shows increased activity in fibromyalgia and hence modulation of the NMDAR is a target for therapeutic intervention. A literature review of interventions impacting on the NMDAR shows a number of drugs to be active on the NMDAR mechanism in fibromyalgia patients, with variable clinical effects. Low-dose intravenous ketamine and oral memantine both show clinically useful benefit in fibromyalgia. However, consideration of side-effects, logistics and cost need to be factored into management decisions regarding use of these drugs in this clinical setting. Overall benefits with current NMDAR antagonists appear modest and there is a need for better strategy trials to clarify optimal dose schedules and to delineate potential longer–term adverse events. Further investigation of the role of the NMDAR in fibromyalgia and the effect of other molecules that modulate this receptor appear important to enhance treatment targets in fibromyalgia.

In Clinical Practice, the Term “Central Sensitivity Score” Is More Useful Than the Term “Polysymptomatic Distress Scale”: Comment on the Editorial by Wolfe

To the Editor: We read with interest the recent editorial by Dr. Wolfe (1), in which he summarized the status of the American College of Rheumatology (ACR) 2010 preliminary diagnostic criteria for fibromyalgia (2) and the 2011 modification of those criteria (3). He notes that the 2 components of the 2010 criteria, the Widespread Pain Index and the Symptom Severity Scale, can be summated, and that the resultant score that is obtained will fall within a defined range, allowing a “fibromyalgia symptom scale” to be constructed (3). This score not only can define whether a patient meets the criteria for a diagnosis of fibromyalgia but also can indicate where the patient is on the “continuum of distress,” regardless of whether he or she has fibromyalgia. The features of fibromyalgia represent a continuous variable. Higher levels within the fibromyalgia symptom scale are more likely to be associated with fibromyalgia, and lower levels are less likely to do so. Because the scale can predict associations with characteristics of fibromyalgia (e.g., pain, poor sleep, fatigue), it has also been termed the “fibromyalgianess” scale (3). This scale has subsequently been termed the Polysymptomatic Distress (PSD) Scale, a term that is linked to previous associations between multiple symptoms and emotional distress (4,5). We agree that the modified version of the 2010 ACR criteria (now termed the fibromyalgia research criteria [6]) and the derived scale are significant advances for research into fibromyalgia in a wide range of clinical settings, including those outside rheumatology. Nonetheless, not everyone has adopted the term PSD Scale. For instance, in a recent study, this scale was referred to as the “fibromyalgia survey score” (7). The designated term PSD Scale implies that the scale is measuring distress and that by implication, emotional distress might be the key factor in fibromyalgia symptoms. We do not necessarily disagree with that proposition but believe that a broader term might be more useful within the wider medical community, and also to our patients. In our clinical practice, we now refer to this scale as the central sensitivity score, after initially considering the term central pain score. We believe that the score is measuring features that relate to central rather than peripheral factors in both normal persons and patients with fibromyalgia. Although pain is the dominant element contributing to the score, other critical non-pain symptoms are also rated (8). The scale emphasizes and assigns high ratings to levels of sleep disturbance, fatigue, and cognitive dysfunction, all of which relate to central factors. Other lesser-rated components of the scale include headache, abdominal pain, and depression. These elements can also have a large central component. This term thus highlights the key mechanism of sensitization in fibromyalgia and related disorders (9). Additionally, the number of pain regions reported by the patient also equates to the mechanism of central sensitivity. The more pain regions that are reported, the more there is centralization of the pain mechanism. Hence, we propose the term “central sensitivity score” rather than “polysymptomatic distress scale,” “fibromyalgianess scale,” or “fibromyalgia survey score.” The implications and clinical usefulness of the score may be expanded by this proposed alternative name, and more clinicians, including nonrheumatologists, might be disposed to use the score if fibromyalgia, “fibromyalgianess,” or “polysymptomatic distress” are not emphasized in the name.

Fibromyalgia has a high prevalence and impact in cardiac failure patients

Objective Chronic cardiac failure (CCF) shares several clinical features with fibromyalgia (FM), a syndrome of increased central sensitivity and musculoskeletal pain. FM frequently coexists with other chronic illness. Musculoskeletal pain is reported in patients with CCF; however, the prevalence and impact of FM in patients with CCF is not known. This research aims to assess the prevalence and effects of concurrent FM in patients with CCF and to identify other coexisting central sensitivity syndromes. Material and Methods In a cross-sectional study, demographic, clinical, and functional information was gathered from participants with CCF from public and private clinics. Cardiac failure severity was rated using the New York Heart Association (NYHA) scale. FM diagnosis was determined using 2011 American College of Rheumatology (ACR) criteria. The short-form 36 (SF-36) assessed overall health function. Results Of the 57 CCF participants (63.2% male, mean age 70.3 years), 22.8% (n=13) met FM diagnostic criteria. CCF patients with FM had poorer outcomes across multiple SF-36 domains (p<0.05), compared to those without, despite having comparable CCF severity. Those with FM were more likely to report other central sensitivity syndromes, especially temporomandibular joint dysfunction (mean Δ=23%, p<0.05), headache (mean Δ=28.8%, p<0.05), and irritable bladder (mean Δ=14%, p<0.05). Conclusion High prevalence of FM was found in patients with CCF. This was associated with increased likelihood of other comorbid central sensitivity syndromes and with poorer clinical outcomes. The recognition of coexisting FM in patients with CCF provides an important opportunity to improve health outcomes by managing FM-related symptoms, in addition to symptoms that relate specifically to CCF.