Articles: pain-management.
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An ACVR1 activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans.
Altered bone morphogenetic protein (BMP) signaling is associated with many musculoskeletal diseases. However, it remains unknown whether BMP dysfunction has direct contribution to debilitating pain reported in many of these disorders. Here, we identified a novel neuropathic pain phenotype in patients with fibrodysplasia ossificans progressiva (FOP), a rare autosomal-dominant musculoskeletal disorder characterized by progressive heterotopic ossification. ⋯ Although there was no major effect of ACVR1 R206H on differentiation and maturation of nociceptive sensory neurons (iSNs) derived from FOP induced pluripotent stem cells, both intracellular and extracellular electrophysiology analyses of the ACVR1 R206H iSNs displayed ACVR1-dependent hyperexcitability, a hallmark of neuropathic pain. Consistent with this phenotype, we recorded enhanced responses of ACVR1 R206H iSNs to TRPV1 and TRPA1 agonists. Thus, activated ACVR1 signaling can modulate pain processing in humans and may represent a potential target for pain management in FOP and related BMP pathway diseases.
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Chronic non-cancer pain (CNCP) is common among frequent emergency department (ED) users, although factors underlying this association are unclear. This study estimated the association between sustained opioid use and frequent ED use among patients with CNCP. ⋯ Due to confounding by social and medical vulnerability, patients with CNCP with sustained opioid use appear to have a higher propensity for frequent ED use in unadjusted models. However, sustained opioid use was not associated with frequent ED use in these patients after adjustment.
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Nerve trauma-induced alternations of gene expression in the neurons of dorsal root ganglion (DRG) participate in nerve trauma-caused nociceptive hypersensitivity. Transcription factors regulate gene expression. Whether the transcription factor E74-like factor 1 (ELF1) in the DRG contributes to neuropathic pain is unknown. ⋯ Mechanistically, more ELF1 directly bond to and activated Mmp9 promoter in injured DRG neurons after CCI. Our data indicate that ELF1 participates in nerve trauma-caused nociceptive hypersensitivity likely through upregulating MMP9 in injured DRG. E74-like factor 1 may be a new target for management of neuropathic pain.
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Peripheral nerve blocks for pain management have historically been discussed in anesthesiology literature but, until recently, have not been considered in emergency medicine contexts. Transversus abdominis plane (TAP) blocks, in particular, have recently been explored in the emergency department for pain control in acute appendicitis but are potentially helpful for managing abdominal pain of other etiologies. ⋯ She was found to have a large rectus sheath hematoma on computed tomography. An ultrasound-guided transversus abdominis plane block was performed in the emergency department, and the patient had complete resolution of her pain.
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Review
Single-cell RNA sequencing in the context of neuropathic pain: Progress, challenges, and prospects.
Neuropathic pain, characterized by persistent or intermittent spontaneous pain as well as some unpleasant abnormal sensations, is one of the most prevalent health problems in the world. Ectopic nerve activity, central and peripheral nociceptive sensitization and many other potential mechanisms may participate in neuropathic pain. The complexity and ambiguity of neuropathic pain mechanisms result in difficulties in pain management, and existing treatment plans provide less-than-satisfactory relief. ⋯ Although scRNA-seq is a relatively new technique in the neuropathic pain field, there have been several studies based on animal models. However, because of the various differences between animals and humans, more attention should be given to translational medicine research. With the aid of scRNA-seq, researchers can further explore the mechanism of neuropathic pain to improve the clinical understanding of the diagnosis, treatment and management of neuropathic pain.