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Interdisciplinary pain rehabilitation (IPR) usually employs a cognitive-behavioural therapeutic (CBT) approach. However, there is growing support for chronic pain treatments based on acceptance and commitment therapy (ACT). Most studies of ACT and CBT for chronic pain have evaluated their effects after psychological interventions, not after IPR. We compared the results of an ACT-based IPR programme with two CBT-based IPR programmes.
Learn More >Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat neuropathic pain but the quality of evidence remains low. We aimed to assess the efficacy and safety of neuronavigated rTMS to the motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) in neuropathic pain over 25 weeks. We did a randomised double-blind, placebo-controlled trial at four outpatient clinics in France. Patients aged 18-75 years with peripheral neuropathic pain were randomly assigned in a 1:1 ratio to M1 or DLPFC-rTMS and re-randomised in a 2:1 ratio to active or sham rTMS (10 Hz, 3000 pulses/session, 15 sessions over 22 weeks). Patients and investigators were blind to treatment allocation. The primary endpoint was the comparison between active M1-rTMS, active DLPCF-rTMS and sham-rTMS for the change over the course of 25 weeks (group by time interaction) in average pain intensity (from 0 no pain to 10 maximal pain) on the Brief Pain Inventory (BPI), using a mixed model repeated measures analysis in patients who received at least one rTMS session (modified ITT population). Secondary outcomes included other measures of pain intensity and relief, sensory and affective dimensions of pain, quality of pain, self reported pain intensity and fatigue (patients diary), patient and clinician global impression of change (PGIC, CGIC), quality of life, sleep, mood and catastrophizing. This study is registered with ClinicalTrials.gov NCT02010281. A total of 152 patients were randomised and 149 received treatment (49 for M1; 52 for DLPFC; 48 for sham). M1-rTMS reduced pain intensity versus sham-rTMS (estimate for group x session interaction: -0.048 ± 0.02; 95% CI: -0.09 to -0.01; p = 0.01). DLPFC-rTMS was not better than sham (estimate: -0.003 ± 0.01; 95% CI:-0.04 to 0.03, p = 0.9). M1-rRMS, but not DLPFC-rTMS, was also superior to sham-rTMS on pain relief, sensory dimenson of pain, self reported pain intensity and fatigue, PGIC and CGIC. There were no effect on quality of pain, mood, sleep and quality of life as all groups improved similarly over time. Headache was the most common side effect and occurred in 17 (34.7%), 23 (44.2%) and 13 (27.1%) patients from M1, DLPFC and sham groups respectively (p = 0.2). Our results support the clinical relevance of M1-rTMS, but not of DLPFC-rTMS, for peripheral neuropathic pain with an excellent safety profile.
Learn More >Fibromyalgia syndrome (FMS) is a highly prevalent, debilitating disease with heterogeneous symptoms of widespread pain and tenderness, fatigue, sleep disturbance, and impaired cognition. The cause of FMS is unknown, but the clinical constellation of symptoms and abnormalities in the neuroendocrine system, autonomic nervous system, and sleep implicate the nervous system in its pathogenesis. In this issue of the JCI, Goebel, Krock, et al. identified antibodies from patients with FMS that produce FMS in mice by binding to satellite glial cells (SGCs), which envelope sensory neurons. Because antibodies harvested from patients with FMS, but not controls, stimulated SGCs to an activated state known to mediate chronic pain by augmenting neuronal activity, these findings reveal a pivotal role for autoreactive IgG in the pathophysiology of FMS. These important findings pave a pathway to study mechanism-based experimental therapeutics targeting IgG titers or antibody binding to SGCs underlying the neuroimmune dysfunction of FMS.
Learn More >The incidence rate of neck pain is increasing worldwide, and the disease is associated with a high social burden. Manual therapy has been widely applied in the treatment of neck pain, but a high-quality, pragmatic randomized clinical trial for this treatment has not been conducted to date.
Learn More >Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nociceptive fibers in skin-nerve preparations from mice treated with FMS IgG displayed an increased responsiveness to cold and mechanical stimulation. These mice also displayed reduced locomotor activity, reduced paw grip strength, and a loss of intraepidermal innervation. In contrast, transfer of IgG-depleted serum from FMS patients or IgG from healthy control subjects had no effect. Patient IgG did not activate naive sensory neurons directly. IgG from FMS patients labeled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG), but no cells in the spinal cord. Furthermore, FMS IgG bound to human DRG. Our results demonstrate that IgG from FMS patients produces painful sensory hypersensitivities by sensitizing peripheral nociceptive afferents and suggest that therapies reducing patient IgG titers may be effective for fibromyalgia.
Learn More >The Centers for Disease Control and Prevention (CDC) released the "Guideline For Prescribing Opioids For Chronic Pain" (hereafter, CDC guideline) in 2016, but its association with prescribing practices for patients who are opioid naive is unknown.
Learn More >Legalization of cannabidiol (CBD) products has ignited interest in clinical practice and research. One desired indication includes possible pain-relieving effects of CBD. The purposes of the current article are to (1) clarify terminology relevant to cannabinoids; (2) explain and understand the pharmacotherapeutics of CBD; (3) examine research of the current use of CBD by older adults for treating pain; (4) discuss safety considerations with using CBD products; and (5) provide best practice recommendations for clinicians as they advise their older adult patients. A review of the literature demonstrated mixed results on the efficacy of CBD in relieving pain in older adults. There is inconsistency in the labeling of over-the-counter CBD products that can result in safety issues and will require more federal quality control. Likewise, gaps in knowledge regarding safety and efficacy of CBD use in older adults are vast and require further research. [(7), 6-15.].
Learn More >We tested the hypothesis that the cognitive impairment associated with inflammatory pain may result from dysregulation of the top-down control of locus ceruleus's (LC) activity by the medial prefrontal cortex (mPFC). Injection of complete Freund's adjuvant (CFA) served as a model for inflammatory pain. The CFA injection decreased the thermal thresholds in both sexes but only the male mice showed increased anxiety-like behavior and diminished cognition, while the females were not affected. Increased calcium fluorescence, a marker for neuronal activity, was detected by photometry in the mPFC of males but not in females with CFA. Next, while chemogenetic inhibition of the projections from the mPFC to the LC improved the object recognition memory of males with pain, the inhibition of the mPFC to LC pathway in female mice produced anxiolysis and spatial memory deficits. The behavior results prompted us to compare the reciprocal innervation of mPFC and LC between the sexes. We used an anterograde transsynaptic tagging technique, which relies on postsynaptic cre transfer, to assess the innervation of LC by mPFC efferents. The males showed a higher rate of postsynaptic cre transfer into LC neurons from mPFC efferents than the females. And vice versa, a retrograde tracing experiment demonstrated that LC to mPFC projection neurons were more numerous in females when compared to males. In conclusion, we provide evidence that subtle differences in the reciprocal neuronal circuit between the LC and mPFC may contribute to sex differences associated with the adverse cognitive effects of inflammatory pain.
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