Articles: neuropathic-pain.
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Nociceptors with somata in dorsal root ganglia (DRGs) readily switch from an electrically silent state to a hyperactive state of tonic, nonaccommodating, low-frequency, irregular discharge of action potentials (APs). Spontaneous activity (SA) during this state is present in vivo in rats months after spinal cord injury (SCI) and has been causally linked to SCI pain. Intrinsically generated SA and, more generally, ongoing activity (OA) are induced by various neuropathic conditions in rats, mice, and humans and are retained in nociceptor somata after dissociation and culturing, providing a powerful tool for investigating its mechanisms and functions. ⋯ The most consistent electrophysiological alteration associated with OA was enhancement of DSFs. An unexpected discovery after plantar incisions was hyperexcitability in neurons from thoracic DRGs that innervate dermatomes distant from the injured tissue. Potential in vivo functions of widespread, low-frequency nociceptor OA consistent with these and other findings are to contribute to hyperalgesic priming and to drive anxiety-related hypervigilance.
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Neuropathic pain remains difficult to treat, with drug development hampered by an incomplete understanding of the pathogenesis of the condition, as well as a lack of biomarkers. The problem is compounded by the scarcity of relevant human peripheral tissues, including skin, nerves, and dorsal root ganglia. Efforts to obtain such samples are accelerating, increasing the need for standardisation across laboratories. ⋯ We achieved consensus on minimal recommended phenotyping, harmonised wet laboratory protocols, statistical design, reporting, and data sharing. Here, we also share a variety of relevant standard operating procedures as supplementary protocols. We envision that our recommendations will help unify human tissue research in the field and accelerate our understanding of how abnormal interactions between sensory neurons and their local peripheral environment contribute towards neuropathic pain.
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Chemotherapy-induced peripheral neuropathic pain aggravates cancer survivors' life burden. Electroacupuncture (EA) has exhibited promising analgesic effects on neuropathic pain in previous studies. We investigated whether EA was effective in a paclitaxel-induced neuropathic pain mouse model. ⋯ Electroacupuncture effectively alleviated paclitaxel-induced mechanical allodynia, and the effect was attenuated by the chemogenetic activation of astrocytes in the RVM. In addition, inhibiting astrocytic calcium activity by using either IP3R2 knockout (IP3R2 KO) mice or microinjection of AAV-mediated hPMCA2 w/b into the RVM to reduce non-IP3R2-dependent Ca2+ signaling in astrocytes exhibited an analgesic effect on neuropathic pain, which mimicked the EA effect. The current study revealed the pivotal role of the RVM astrocytes in mediating the analgesic effects of EA on chemotherapy-induced peripheral neuropathic pain.
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Gabapentinoids are commonly prescribed to control neuropathic pain of lumbar radiculopathy. Few trials have compared the efficacy of gabapentin (GBP) and pregabalin (PGB). Therefore, the authors conducted a meta-analysis to compare the difference in effect between GBP and PGB in lumbar radiculopathy patients. ⋯ Based on this article, the existing evidence suggests that PGB was more effective in reducing pain of lumbar radiculopathy compared to GBP at the short-term follow-up, but there was no difference in the long-term follow-up. Physicians should consider this finding in prescribing medications for patients with lumbar radiculopathy.
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The sodium-activated potassium channel Slack (KNa1.1, Kcnt1) plays a critical role in tuning neuronal excitability. Previous studies have revealed that Slack is expressed in neurons of the superficial dorsal horn of the spinal cord. However, the precise role of Slack in spinal dorsal horn neurons is unclear. ⋯ Unexpectedly, Lbx1-Slack-/- mice demonstrated increased scratching after intradermal injection of chloroquine, LY344864, and histamine. Moreover, neuromedin B receptors are coexpressed with Slack in the dorsal horn, and scratching after intrathecal delivery of neuromedin B was increased in Lbx1-Slack-/- mice. Our study provides in vivo evidence that Slack expressed in spinal dorsal horn neurons inhibits nerve injury-induced allodynia and acute itch induced by various pruritogens.