Articles: hyperalgesia.
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We have recently reported that intraperitoneal (i.p.) injection of thymulin at low doses (50 ng) resulted in thermal and mechanical hyperalgesia and upregulation of the level of interleukin-1beta in the liver. In this study, we demonstrate that such injections of thymulin result in a significant elevation in the levels of TNF-alpha (P<0.01), NGF (P<0.01) and PGE(2) (P<0.01) in the liver of the treated rats, in addition to the increase in the levels of IL-1beta. Pretreatment with specific antagonists to each of these factors (polyclonal anti-TNF-alpha, anti-NGF antiserum and IL-1 receptor antagonist) did not result in the abolition of the hyperalgesia as assessed by the paw pressure, hot plate, paw immersion and tail flick tests. ⋯ The cyclooxygenase inhibitor, meloxicam, reversed in a dose dependent manner (0.2, 0.4 and 2 mg/kg) thymulin effects as assessed by the different pain tests. It also abolished the thymulin-induced increase in the level of cytokines and NGF in the liver. Our results indicate that PGE(2) could be the key mediator of the hyperalgesic action of thymulin and the observed upregulation of proinflammatory cytokines and NGF.
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Fundam Clin Pharmacol · Jul 2000
Tramadol relieves thermal hyperalgesia in rats with chronic constriction injury of the sciatic nerve.
The present study was designed to test whether tramadol is effective in the control of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve was induced over the left hind limb in male Sprague-Dawley rats. Identical surgery was performed on the opposite side except that the sciatic nerve was not ligated (sham surgery). ⋯ Tramadol also resulted in a decreased sensitivity to thermal stimulus on the sham limb both in acute and semi-chronic administration. We conclude that both acute and semi-chronic tramadol treatment relieves thermal hyperalgesia effectively in rats with CCI of the sciatic nerve. This indicates that tramadol shows promise as a potential treatment for relief of neuropathic pain in humans.
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Arch Phys Med Rehabil · Jul 2000
Effect of varying frequency, intensity, and pulse duration of transcutaneous electrical nerve stimulation on primary hyperalgesia in inflamed rats.
To examine the effect of varying frequency, intensity, and pulse duration of transcutaneous electrical nerve stimulation (TENS) on primary hyperalgesia (increased response to a noxious stimuli) to heat and mechanical stimuli induced by carrageenan paw inflammation in rats. ⋯ High-frequency TENS reduces primary hyperalgesia to heat and mechanical stimuli for up to 1 day after treatment. In contrast, low-frequency TENS is ineffective in reducing primary hyperalgesia. Varying intensity or pulse duration had no effect on the degree of antihyperalgesia produced by high-frequency TENS.
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1. The effect of IL-1ra on response to intraplantar (i.pl.) injection of LPS, carrageenin, bradykinin, TNFalpha, IL-1beta, IL-8, PGE(2) and dopamine was investigated in a model of mechanical hyperalgesia in rats. 2. IL-1ra inhibited hyperalgesic response to LPS, carrageenin, bradykinin, TNFalpha, and IL-1beta, but not responses to IL-8, PGE(2) and dopamine. 3. ⋯ In mice, IL-1ra inhibited the nociceptive response to i.p. injection of acetic acid. 7. These data suggest that IL-1ra, released at sites of inflammation, limits inflammatory hyperalgesia. This effect is independent of (IL-1ra-induced) IL-4 and IL-10 and appears to be the result of antagonism by IL-1ra of IL-1beta-stimulated eicosanoid production.
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We have identified a mechanism, mediated by the epsilon isozyme of protein kinase C (PKCepsilon) in peripheral neurons, which may have a role in chronic inflammatory pain. Acute inflammation, produced by carrageenan injection in the rat hindpaw, produced mechanical hyperalgesia that resolved by 72 hr. However, for up to 3 weeks after carrageenan, injection of the inflammatory mediators prostaglandin E(2) or 5-hydroxytryptamine or of an adenosine A(2) agonist into the same site induced a markedly prolonged hyperalgesia (>24 hr compared with 5 hr or less in control rats not pretreated with carrageenan). ⋯ Acute carrageenan hyperalgesia could be inhibited by PKA or PKG antagonists. However, these antagonists did not inhibit development of the hypersensitivity to inflammatory mediators. Our findings indicate that different second messenger pathways underlie acute and prolonged inflammatory pain.