Mol Pain
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GABAergic system disinhibition played an important role in the pathogenesis of remifentanil-induced hyperalgesia (RIH). K+-Cl--cotransporter-2 (KCC2) has the potential to enhance the strength of GABAergic signaling function. However, few reports have focused on the additive analgesic effect of KCC2 enhancer and GABAA receptor agonist on the spinal dorsal horn. ⋯ Taken together, these findings suggested that the RIH was initiated by decreased GABA release. Downregulation of GABAAα2R and KCC2 receptor contributed to spinally mediated hyperalgesia in RIH. KCC2 enhancer was proved to potentiate antinociceptive effect of GABAAR agonist in RIH.
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Trigeminal neuropathic pain has been modeled in rodents through the constriction of the infraorbital nerve (CCI-ION). Sensory alterations, including spontaneous pain, and thermal and mechanical hyperalgesia are well characterized, but there is a notable lack of evidence about the affective pain component in this model. Evaluation of the emotional component of pain in rats has been proposed as a way to optimize potential translational value of non-clinical studies. ⋯ Amphetamine caused a marked increase in 50 kHz USV emission in CCI-ION rats. In addition, TH expression was lower in constricted animals and c-Fos analysis revealed an increase in neuronal activation. Taken together, these data indicate that CCI-ION causes a reduction in the emission of environmental-induced appetitive calls concomitantly with facial mechanical hyperalgesia and that both changes may be related to a reduction in the mesolimbic dopaminergic activity.
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Tumor metastasis to bone is often accompanied by a severe pain syndrome (cancer-induced bone pain, CIBP) that is frequently unresponsive to analgesics, which markedly reduces patient quality of life and cancer treatment tolerance in patients. Prolonged pain can induce hypersensitivity via spinal plasticity, and several recent studies have implicated the involvement of vascular endothelial growth factor-A (VEGF-A) signaling in this process. Here, we speculated that CIBP is associated with VEGF-A/VEGFR2 signaling in the spinal cord. ⋯ Conversely, the intrathecal injection of exogenous VEGF-A was sufficient to cause pain hypersensitivity in naïve mice via the VEGFR2-mediated activation of protein kinase C. Moreover, the spinal blockade of VEGF-A or VEGFR2 also suppressed N-methyl-D-aspartate receptor (NMDAR) activation and downstream Ca2+-dependent signaling. Thus, spinal VEGF-A/VEGFR2/NMDAR signaling pathways may be critical mediators of CIBP.
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Offset analgesia is defined by a dramatic drop in perceived pain intensity with a relatively small decrease in noxious input. Although functional magnetic resonance imaging studies implicate subcortical descending inhibitory circuits during offset analgesia, the role of cortical areas remains unclear. The current study identifies cortical correlates of offset analgesia using functional near infrared spectroscopy (fNIRS). ⋯ These data demonstrate opposing cortical activation patterns during offset analgesia and support a model in which right dlPFC underlies ongoing evaluation of pain intensity change. With predictions of decreasing pain intensity, right dlPFC activation likely inhibits ascending noxious input via subcortical pathways resulting in SSC and mPFC deactivation. This study identifies cortical circuitry underlying offset analgesia and introduces the use of fNIRS to study pain modulation in an outpatient clinical environment.
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In the mid-1990s, the development of combination antiretroviral therapy converted HIV infection into a chronic condition, with newly diagnosed patients now living longer than the general population. HIV affects both the central and peripheral nerve systems, resulting in a variety of clinical problems, including peripheral neuropathy, which is a common neurological consequence. Despite this, there is a scarcity of data on the extent of peripheral sensory neuropathy and its underlying factors in Ethiopia, necessitating this study. ⋯ Peripheral sensory neuropathy was incredibly common. Accordingly, peripheral sensory neuropathy was found considerably associated with age, viral load level, stage of the disease, and DM comorbidity. It is vital to integrate routine peripheral sensory neuropathy screening strategies for clients who are on ART follow up for prevention and early identification of the problem.