Mol Pain
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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.
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Orofacial pain disorders are predominately experienced by women. Progesterone, a major ovarian hormone, is neuroprotective and antinociceptive. We recently reported that progesterone attenuates estrogen-exacerbated orofacial pain behaviors, yet it remains unclear what anatomical substrate underlies progesterone's activity in the trigeminal system. ⋯ Trigeminal ganglia were processed by either fluorescent immunochemistry or western blotting to for visualization and quantification of Sig-1R, 5α-reductase, and 3α-hydroxysteroid dehydrogenase. Here we report that Sig-1Rs and both enzymes involved in progesterone metabolism are highly expressed in a variety of nociceptive sensory neuron populations in the female rat trigeminal ganglia at similar levels across the four stages of the estrous cycle. These data indicate that trigeminal sensory neurons are an anatomical substrate for the reported antinociceptive activity of progesterone via Sig-1R and/or conversion to allopregnanolone.
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Thermal nociception involves the transmission of temperature-related noxious information from the periphery to the CNS and is a heritable trait that could predict transition to persistent pain. Rodent forward genetics complement human studies by controlling genetic complexity and environmental factors, analysis of end point tissue, and validation of variants on appropriate genetic backgrounds. Reduced complexity crosses between nearly identical inbred substrains with robust trait differences can greatly facilitate unbiased discovery of novel genes and variants. ⋯ Whole brain proteomics further supported decreased H2AFY expression could underlie enhanced hot plate sensitivity, and identified ACADS as a candidate for reduced brain weight. To summarize, a BALB/c reduced complexity cross combined with multiple-omics approaches facilitated identification of candidate genes underlying thermal nociception and brain weight. These substrains provide a powerful, reciprocal platform for future validation of candidate variants.
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Phantom tooth pain (PTP) is a rare and specific neuropathic pain that occurs after pulpectomy and tooth extraction, but its cause is not understood. We hypothesized that there is a genetic contribution to PTP. We focused on solute carrier family 17 member 9 (SLC17A9)/vesicular nucleotide transporter (VNUT) and purinergic receptor P2Y12 (P2RY12), both of which have been associated with neuropathic pain and pain transduction signaling in the trigeminal ganglion in rodents. ⋯ Therefore, these carriers may be more susceptible to PTP. These results suggest that specific genetic polymorphisms of the SLC17A9 and P2RY12 genes are involved in PTP. This is the first report on genes that are associated with PTP in humans.