Pain
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Alterations in the composition and function of the gut microbiome in women with fibromyalgia have recently been demonstrated, including changes in the relative abundance of certain bile acid-metabolizing bacteria. Bile acids can affect multiple physiological processes, including visceral pain, but have yet to be explored for association to the fibromyalgia gut microbiome. In this study, 16S rRNA sequencing and targeted metabolomic approaches were used to characterize the gut microbiome and circulating bile acids in a cohort of 42 women with fibromyalgia and 42 healthy controls. ⋯ The changes observed in the composition of the gut microbiota and the concentration of circulating secondary bile acids seem congruent with the phenotype of increased nociception and are quantitatively correlated with symptom severity. This is a first demonstration of circulating bile acid alteration in individuals with fibromyalgia, potentially secondary to upstream gut microbiome alterations. If corroborated in independent studies, these observations may allow for the development of molecular diagnostic aids for fibromyalgia as well as mechanistic insights into the syndrome.
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Ectopic discharge ("ectopia") in damaged afferent axons is a major contributor to chronic neuropathic pain. Clinical opinion discourages surgical resection of nerves proximal to the original injury site for fear of resurgence of ectopia and exacerbated pain. We tested this concept in a well-established animal neuroma model. ⋯ Similarly, we saw no indication of resurgent ectopia originating in axotomized dorsal root ganglion neuronal somata and no behavioral reflection of resurgence. In summary, we failed to validate the concern that proximal resection of a problematic nerve would lead to intense resurgent ectopic discharge and pain. As the well-entrenched concept of resurgence is based more on case reports and anecdotes than on solid evidence, it may be justified to relax the stricture against resecting neuromas as a therapeutic strategy, at least within the framework of controlled clinical trials.
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Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. ⋯ Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.
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Targeted muscle reinnervation (TMR) is a clinical intervention that is rapidly becoming common in major limb amputation to prevent or reduce amputation-related pain. However, TMR is much less effective when applied long after injury compared with acute TMR. Since the mechanisms governing pain relief in TMR of amputated nerves are unknown, we developed a preclinical model as a platform for mechanistic examination. ⋯ In this model, the pain phenotype induced by nerve transection is reduced by TMR when performed within 3 weeks after injury. However, TMR delayed 12 weeks after injury fails to reduce pain behaviors. This replicates clinical experience with limb amputation, supporting validity of this model for examining the mechanisms of TMR analgesia.
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Previously, we observed that B cells and autoantibodies mediated chronic nociceptive sensitization in the mouse tibia fracture model of complex regional pain syndrome and that complex regional pain syndrome patient antibodies were pronociceptive in fracture mice lacking mature B cells and antibodies (muMT). The current study used a lumbar spinal disk puncture (DP) model of low back pain in wild-type (WT) and muMT mice to evaluate pronociceptive adaptive immune responses. Spinal disks and cords were collected 3 weeks after DP for polymerase chain reaction and immunohistochemistry analyses. ⋯ Serum collected from WT DP mice and injected into muMT DP mice caused nociceptive sensitization, as did intrathecal injection of IgM collected from WT DP mice, and IgM immune complexes were observed in lumbar spinal disks and cord of WT DP mice. Serum from WT tibia fracture mice was not pronociceptive in muMT DP mice and vice versa, evidence that each type of tissue trauma chronically generates its own unique antibodies and targeted antigens. These data further support the pronociceptive autoimmunity hypothesis for the transition from tissue injury to chronic musculoskeletal pain state.