Articles: hyperalgesia.
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Thermal burns induce pain at the site of injury, mechanical hyperalgesia, associated with a complex time-dependent inflammatory response. To determine the contribution of inflammatory mediators to burn injury-induced mechanical hyperalgesia, we measured dynamic changes in the levels of three potent hyperalgesic cytokines, interleukin IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNFalpha), in skin of the rat, following a partial-thickness burn injury. ⋯ Spinal intrathecal injection of oligodeoxynucleotides antisense for gp130, a receptor subunit shared by members of the IL-6 family of cytokines, attenuated both burn- and intradermal IL-6-induced hyperalgesia, as did intradermal injection of anti-IL-6 function blocking antibodies. These studies suggest that IL-6 is an important mediator of burn-injury pain.
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Comparative Study
Gabapentin prevents delayed and long-lasting hyperalgesia induced by fentanyl in rats.
Opioid-induced hyperalgesia can develop rapidly after opioid exposure. Neuropathic pain and opioid-induced hyperalgesia share common pathophysiologic mechanisms. Gabapentin is effective for the management of neuropathic pain and may therefore prevent opioid-induced hyperalgesia. This study tested the effectiveness of gabapentin for prevention of long-lasting hyperalgesia induced by acute systemic fentanyl in uninjured rats. Involvement of the alpha2delta auxiliary subunits of voltage-gated calcium channels in the prevention of opioid-induced hyperalgesia by gabapentin also was assessed. ⋯ Intraperitoneal and intrathecal gabapentin prevents the development of hyperalgesia induced by acute systemic exposure to opioids. This prevention may result, at least in part, from binding of gabapentin to the alpha2delta auxiliary subunits of voltage-gated calcium channels.
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Painful neuropathy is one of the most common complications of diabetes, one hallmark of which is tactile allodynia (pain hypersensitivity to innocuous stimulation). The underlying mechanisms of tactile allodynia are, however, poorly understood. Emerging evidence indicates that, following nerve injury, activated microglia in the spinal cord play a crucial role in tactile allodynia. ⋯ We also found that a single administration of U0126 reduced the expression of allodynia. Together, these results suggest that activated dorsal horn microglia may be a crucial component of diabetes-induced tactile allodynia, mediated, in part, by the ERK signaling pathway. Thus, inhibiting microglia activation in the dorsal horn may represent a therapeutic strategy for treating diabetic tactile allodynia.
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C5a, a complement activation product, exhibits a broad spectrum of inflammatory activities particularly neutrophil chemoattraction. Herein, the role of C5a in the genesis of inflammatory hypernociception was investigated in rats and mice using the specific C5a receptor antagonist PMX53 (AcF-[OP(D-Cha)WR]). ⋯ These results suggest that C5a is an important inflammatory hypernociceptive mediator, acting by a mechanism independent of hypernociceptive cytokine release, but dependent on the presence of neutrophils. Therefore, we suggest that inhibiting the action of C5a has therapeutic potential in the control of inflammatory pain.
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Using a mouse model of advanced skin cancer which has mixed nociceptive-neuropathic pain, we evaluated the analgesic effects of morphine and analgesic adjuvants. Morphine hydrochloride (10--30 mg/kg, oral) and mexiletine hydrochloride (10--30 mg/kg, intraperitoneal) dose-dependently inhibited thermal hyperalgesia. ⋯ Analgesic tolerance was observed after 6th administration of morphine, and it was not developed until at least 7th administration of mexiletine and baclofen. This mouse model of skin cancer may be useful for the pharmacological evaluation of the effects of opioids and analgesic adjuvants on mixed nociceptive-neuropathic pain of advanced cancer.