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Investigation of hyperalgesia at the spinal transcriptome level indicated that carrageenan-induced inflammation of rat hind paws leads to a rapid but sustained increase in S100A8 and S100A9 expression, two genes implicated in the pathology of numerous inflammatory diseases including rheumatoid arthritis and gout. In situ hybridization revealed that the elevation occurred in neutrophils that migrate...
Electrical stimulation is widely used to assess the function of sensory nerves in humans. In the present study, the threshold current (CT) required to evoke a paw withdrawal response in rats was assessed with stepwise increases in current delivered as sinusoidal stimulation at frequencies of 2000Hz (CT2000), 250Hz (CT250) and 5Hz (CT5). Baseline CT was 840±3μA for CT2000, 267±2μA for CT250 and 165±1μA...
The roles of central protein kinases A and C (PKA and PKC) in various pain states have intensively been investigated during the past decade. The aim of the present study was to investigate the peripheral involvement of PKA and PKC in persistent nociceptive response, evoked pain behaviors, and inflammation induced by subcutaneous (s.c.) injection of bee venom (BV, 0.2mg/50μl) in rats. The effects of...
Acute microinjection of mu-, delta-, or kappa-opioid receptor (MOPr, DOPr, KOPr) agonists into the rostral ventromedial medulla (RVM) produces antinociception. Thermal antinociception produced by MOPr and DOPr agonists is potentiated during inflammation [Hurley RW, Hammond DL. The analgesic effects of supraspinal mu and delta opioid receptor agonists are potentiated during persistent inflammation...
The acid sensing ion channel 3 (ASIC3) is critical for the development of secondary hyperalgesia as measured by mechanical stimulation of the paw following muscle insult. We designed experiments to test whether ASIC3 was necessary for the development of both primary and secondary mechanical hyperalgesia that develops after joint inflammation. We used ASIC3 −/− mice and examined the primary (response...
Although both inflammatory and neural mechanisms have been suggested as potential contributors to Complex Regional Pain Syndrome type I (CRPS-I), the pathogenesis of the syndrome is still unclear. Clinical trials have shown that free radical scavengers can reduce signs and symptoms of CRPS-I, indirectly suggesting that free radicals and increased oxidative stress are involved in the pathogenesis of...
Peripheral inflammation evokes functional and biochemical changes in the periphery and spinal cord which result in central sensitization and hypersensitivity. Inhibitory control systems from the rostral ventromedial medulla (RVM) are also activated. The present study investigates whether endogenous kappa-opioid receptor (KOPr) systems contribute to these neuroadaptations. Inflammation was induced...
Recent studies indicate that ATP and UTP act at G protein-coupled (P2Y) nucleotide receptors to excite nociceptive sensory neurons; nucleotides also potentiate signaling through the pro-nociceptive capsaicin receptor, TRPV1. We demonstrate here that P2Y 2 is the principal UTP receptor in somatosensory neurons: P2Y 2 is highly expressed in dorsal root ganglia and P2Y 2 (−/−)...
Animal studies have documented a critical role for cytokines in cell signaling events underlying inflammation and pain associated with tissue injury. While clinical reports indicate an important role of cytokines in inflammatory pain, methodological limitations have made systematic human studies difficult. This study examined the utility of a human in vivo bioassay combining microdialysis with multiplex...
It has been postulated that the G protein-coupled receptor, GPR55, is a third cannabinoid receptor. Given that the ligands at the CB 1 and CB 2 receptors are effective analgesic and anti-inflammatory agents, the role of GPR55 in hyperalgesia associated with inflammatory and neuropathic pain has been investigated. As there are no well-validated GPR55 tool compounds, a GPR55 knockout...
The glial cytokine, interleukin-1β (IL-1β), potentiates the excitability of nociceptive trigeminal ganglion (TRG) neurons via membrane depolarization following peripheral inflammation. Perforated patch-clamp technique was used this study to show that the mechanism underlying the excitability of small-diameter TRG neurons following inflammation is due to IL-1β. Inflammation was induced by injection...
Sumatriptan and the other triptan drugs target the serotonin receptor subtypes1B, 1D, and 1F (5-HT 1B/D/F ), and are prescribed widely in the treatment of migraine. An anti-migraine action of triptans has been postulated at multiple targets, within the brain and at both the central and peripheral terminals of trigeminal “pain-sensory” fibers. However, as triptan receptors are also located...
The roles of ion channels in sensory neurons were examined in experimental models of muscle pain in the rat. Rats were injected with 50μl of 4% carrageenan or subjected to an eccentric exercise (ECC) of the gastrocnemius muscle (GM). The Randall–Selitto and von Frey tests were performed on the calves to evaluate mechanical hyperalgesia of the muscle. The changes in expression of four genes and proteins...
Clinically, pain is a complex phenomenon consisting of both sensory and affective aberrations that can persist indefinitely. Pre-clinically, several animal paradigms have been established that reliably mimic both the acute and chronic aspects of pain pertinent to the human condition; however, the commonly used behavioral models only assess the sensory component of pain elicited by an evoked nociceptive...
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