Articles: hyperalgesia.
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GABA-A receptor positive allosteric modulators (PAMs) mediate robust analgesia in animal models of pathological pain, in part via enhancing injury-induced loss of GABA-A-α2 and -α3 receptor function within the spinal cord. As yet, a lack of clinically suitable tool compounds has prevented this concept being tested in humans. Prior to assessing the efficacy of GABA-A receptor PAMs in a human volunteer pain model we have compared compounds capable of variously modulating GABA-A receptor function in comparable rat models of capsaicin-induced acute nocifensive flinching behaviour and secondary mechanical hypersensitivity. ⋯ This was surprising as both NS11394 and TPA023 robustly attenuated late phase (6-30 min post-injection) capsaicin-induced flinching, a pain-like behaviour that is putatively driven by peripheral and central sensitizing mechanisms. Diazepam also attenuated capsaicin-induced nocifensive behaviours, albeit at doses previously shown to impair locomotor function. Our data indicate that GABA-A receptor PAMs with optimal selectivity and efficacy profiles reduce centrally-mediated mechanical hypersensitivity in capsaicin-injected rats, an observation that we expect can translate directly to human volunteer studies.
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Zhong Xi Yi Jie He Xue Bao · Dec 2012
Effects of electroacupuncture on expression of c-fos protein in the spinal dorsal horn of rats with chronic visceral hyperalgesia.
Acupuncture is widely used in clinics to suppress chronic visceral pain in patients with irritable bowel syndrome (IBS); however, the exact neurobiological mechanisms for its therapeutic effects need further exploration. The aim of this study was to investigate the possible involvement of spinal neurons in the effects of electroacupuncture (EA) in relieving chronic visceral hyperalgesia in a rat model of IBS. ⋯ The abnormally high neuronal excitability in the spinal dorsal horn may be an important reason underlying the visceral hyperalgesia in IBS model rats. EA treatment can relieve the chronic visceral hyperalgesia in IBS rats by suppressing the abnormal neuronal excitability in the spinal dorsal horn.
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Neuropathic pain after nerve injuries is characterized by positive and negative sensory symptoms and signs. The extent of sensory fiber loss after nerve injuries has been demonstrated to correlate with symptoms of neuropathic pain by quantitative sensory testing and confirmed by biopsies of small nerve fibers. However, the relationship between the pathologic changes of large nerves on injuries and resulting pain symptoms remains unclear. ⋯ Transient injuries on sensory fibers can produce either positive or negative symptoms of neuropathic pain, and the different extent of sensory fiber loss after different degrees of injuries might account for the varied resulting symptoms of neuropathic pain.
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We have to trust the patient. Pain is undertreated. Inadequate treatment has adverse consequences. ⋯ They are responsive to opioid analgesia. They need baseline opioids ("opioid debt"), mostly a well-stabilized OST. They require higher doses, more frequent dosing and longer opioid administration.
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We previously demonstrated that intrathecal IL-1β caused thermal hyperalgesia in rats. This study was conducted to examine the effects and cellular mechanisms of glial inhibitors on IL-1β-induced nociception in rats. The effects of minocycline (20 μg), fluorocitrate (1 nmol), and SB203580 (5 μg) on IL-1β (100 ng) treatment in rats were measured by nociceptive behaviors, western blotting of p38 mitogen-activated protein kinase (MAPK) and inducible nitric oxide synthase (iNOS) expression, cerebrospinal fluid nitric oxide (NO) levels, and immunohistochemical analyses. ⋯ Minocycline, fluorocitrate, or SB203580 pretreatment suppressed this IL-1β-upregulated P-p38 MAPK mainly in microglia and iNOS mainly in astrocytes; minocycline exhibited the most potent effect. Minocycline and fluorocitrate pretreatment abrogated IL-1β-induced NO release and thermal hyperalgesia in rats. In conclusion, minocycline, fluorocitrate, and SB203580 effectively suppressed the IL-1β-induced central sensitization and hyperalgesia in rats.