Articles: hyperalgesia.
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Visceral injury has been shown to alter somatic sensitivity, but little is known about the effect of somatic insult on the viscera. In the present study, we examined (1) the effect of colon inflammation on somatic sensitivity and (2) the affect of hind paw incision on colon sensitivity. After intracolonic administration of trinitrobenzene sulfonic acid (TNBS) or zymosan, visceromotor responses to colorectal distension were increased to post-treatment day 8. Mechanical withdrawal thresholds in the hind paw were decreased in TNBS- and in zymosan-treated rats until post-intracolonic treatment day 2. There was no change in hind paw heat withdrawal latency in either group. Plantar incision of the hind paw resulted in a decrease in both hind paw mechanical withdrawal threshold and heat withdrawal latency and significantly increased the visceromotor response to colorectal distension from postincision days 1 to 8. The colon hypersensitivity was of longer duration than hyperalgesia at the site of hind paw incision. These results support the hypothesis that somatic injury and visceral inflammation can alter central processing of visceral and somatic inputs, respectively. ⋯ Surgical procedures are common and typically associated with hyperalgesia at and around the site of incision. This report establishes in a model of postsurgical pain and hyperalgesia that a long-lasting visceral hypersensitivity may also accompany postsurgical hyperalgesia.
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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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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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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.
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The vanilloid receptor 1 (VR1) is expressed by the type II A-delta and C-fiber neurons, functioning as a molecular integrator for nociception. VR1 can be selectively ablated by resiniferatoxin (RTX), an ultra-potent excitotoxic agonist, when injected into sensory ganglia. ⋯ VR1-positive neurons are essential for the development of mechanical allodynia. In rats already exhibiting neuropathic pain, the VR1-positive neurons mediate the most sensitive part of mechanical allodynia. RTX injection in sensory ganglia may represent a novel treatment for neuropathic pain.