Articles: hyperalgesia.
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Mechanical allodynia is a cardinal sign of several inflammatory pain disorders where nerve growth factor, a prototypic neurotrophin, plays a crucial role by binding to TrkA receptors. Here, we took the advantage of our generated knock-in mouse model expressing a chimeric TrkA/TrkC receptor that seems to not specifically develop mechanical allodynia after inflammation, to identify the TrkA downstream pathways involved in this phenomenon. ⋯ Inflammatory reaction (oedema, IL-6 content), pain behaviours after intraplantar capsaicin, as well as TRPV1 calcium imaging response of dorsal root ganglion neurons were similar between TrkAC and WT mice. This deficiency in mechanical allodynia development in TrkAC mice is likely due to the alteration of the expression of different TrkA transduction pathways (ie, Akt, p38 MAPK, and c-Jun) especially p38 MAPK, in the dorsal root ganglion cell bodies, ultimately leading to an alteration of at least, ASIC3 channel overexpression, known to participate in nociceptor mechanosensory function.
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Experimental neurology · May 2020
Upregulation of transcription factor 4 downregulates NaV1.8 expression in DRG neurons and prevents the development of rat inflammatory and neuropathic hypersensitivity.
The voltage sodium channel 1.8 (NaV1.8) in the dorsal root ganglion (DRG) neurons contributes to the initiation and development of chronic inflammatory and neuropathic pain. However, an effective intervention on NaV1.8 remains to be studied in pre-clinical research and clinical trials. In this study, we aimed to investigate whether transcription factor 4 (TCF4) overexpression represses NaV1.8 expression in DRG neurons, thus preventing the development of chronic pain. ⋯ We showed that the intrathecal delivery of TCF4 overexpression virus significantly repressed the increase of NaV1.8 and prevented the development of hyperalgesia in rats. Moreover, we confirmed the efficient role of an overexpressed TCF4 in preventing the CFA- and SNI-induced neuronal hyperexcitability by calcium imaging. Our results suggest that attenuating the dysregulation of NaV1.8 by targeting TCF4 may be a novel therapeutic strategy for chronic inflammatory and neuropathic pain.
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Sodium-potassium-chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) are associated with the transmission of peripheral pain. We investigated whether the increase of NKCC1 and KCC2 is associated with peripheral pain transmission in dorsal root ganglion neurons. To this aim, rats with persistent hyperalgesia were randomly divided into four groups. ⋯ In addition, bumetanide can achieve analgesic effects. All experiments were approved by the Institutional Ethics Review Board at the First Affiliated Hospital, College of Medicine, Shihezi University, China on February 22, 2017 (approval No. A2017-169-01).
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Opioid-induced hyperalgesia (OIH) is a phenomenon whereby opioids increase patients' pain sensitivity, complicating their use in analgesia. We explored practitioners' attitudes towards, and knowledge concerning diagnosis, risk factors, and treatment of OIH. ⋯ Most clinicians agreed that OIH is a complication of opioid therapy, but were divided regarding the prevalence of OIH, etiological factors, and optimal management.
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Burn injury pain is a significant public health problem. Burn injury treatment has improved tremendously in recent decades. However, an unintended consequence is that a larger number of patients now survive more severe injuries, and face intense pain that is very hard to treat. ⋯ This ligand-specific signaling by different opioids implies that burn injury may reduce the antinociceptive potency of opioids to different degrees, in a drug-specific manner. Indeed, recent findings hint at drug-specific differences in the ability of opioids to manage burn pain early after injury, as well as differences in their ability to prevent or treat the development of chronic and neuropathic pain. Here we review the current state of opioid treatment, as well as new findings that could potentially lead to opioid-based pain management strategies that may be significantly more effective than the current solutions.