Articles: hyperalgesia.
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Comparative Study
Intrathecal interleukin-1beta administration induces thermal hyperalgesia by activating inducible nitric oxide synthase expression in the rat spinal cord.
The effect of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) on the inducible nitric oxide synthase-nitric oxide (iNOS-NO) cascade in nociceptive signal transduction was examined in the intact rat spinal cord. All rats were implanted with an intrathecal (i.t.) catheter; some were also implanted with an i.t. microdialysis probe. The paw withdrawal latency to radiant heat was used to assess thermal hyperalgesia. ⋯ Neither 1400W nor artificial CSF (aCSF) affected the thermal nociceptive threshold and NO production. These results demonstrate that i.t. administration of IL-1beta induced thermal hyperalgesia by activating the iNOS-NO cascade in the rat spinal cord. On the basis of the present findings, we suggest that i.t. administration of iNOS inhibitors may have potential in the treatment of inflammatory and neuropathic pain syndromes.
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Comparative Study
Antihyperalgesic effects of cizolirtine in diabetic rats: behavioral and biochemical studies.
Although clinically well controlled at the metabolic level, type I diabetes resulting from an insufficient insulin secretion remains the cause of severe complications. In particular, diabetes can be associated with neuropathic pain which fails to be treated by classical analgesics. In this study, we investigated the efficacy of a novel non opioid analgesic, cizolirtine, to reduce mechanical hyperalgesia associated with streptozotocin (STZ)-induced diabetes, in the rat. ⋯ Measurements of the spinal release of calcitonin gene-related peptide (CGRP) through intrathecal perfusion under halothane-anesthesia showed that acute administration of cizolirtine (80 mg/kg, i.p.) significantly diminished (-36%) the peptide outflow in diabetic rats suffering from neuropathic pain. This effect as well as the antihyperalgesic effect of cizolirtine were prevented by the alpha(2)-adrenoreceptor antagonist idazoxan (2 mg/kg, i.p.). These data suggest that the antihyperalgesic effect of cizolirtine in diabetic rats suffering from neuropathic pain implies an alpha(2)-adrenoceptor-dependent presynaptic inhibition of CGRP-containing primary afferent fibers.
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Experimental neurology · Jul 2004
Differential effect of anterior cingulate cortex lesion on mechanical hypersensitivity and escape/avoidance behavior in an animal model of neuropathic pain.
Various limbic system structures have been implicated in processing noxious information. One such structure is the anterior cingulate cortex (ACC), a region that is thought to modulate higher order processing of noxious input related to the affective/motivational component of pain. The present experiment examined the involvement of the ACC in higher order pain processing by measuring paw withdrawal threshold and escape/avoidance responses in the L5 spinal nerve ligation model of neuropathic pain before and following electrolytic lesion of the ACC. ⋯ ACC lesion in animals with L5 ligation did not alter mechanical hypersensitivity, but did significantly decrease escape/avoidance behavior. Anxiety, as measured using the light-enhanced startle paradigm, was not altered by ACC lesion. These results highlight the utility of novel behavioral test paradigms and provide additional support for the role of the ACC in higher order processing of noxious information, suggesting that ACC lesions selectively decrease negative affect associated with neuropathy-induced hypersensitivity.
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Comparative Study
Prostaglandin E2 in the midbrain periaqueductal gray produces hyperalgesia and activates pain-modulating circuitry in the rostral ventromedial medulla.
Recent years have seen significant advances in our understanding of the peripheral and spinal mechanisms through which prostaglandins contribute to nociceptive sensitization. By contrast, the possibility of a supraspinal contribution of these compounds to facilitated pain states has received relatively little attention. One possible mechanism through which prostaglandins could act supraspinally to facilitate nociception would be by recruitment of descending facilitation from brainstem pain-modulating systems. ⋯ Microinjection of PGE(2) (50 fg in 200 nl) into the PAG produced a significant decrease in paw withdrawal latency. The PGE(2) microinjection activated on-cells, RVM neurons thought to facilitate nociception, and suppressed the firing of off-cells, RVM neurons believed to have an inhibitory effect on nociception. These data demonstrate a prostaglandin-sensitive descending facilitation from the PAG, and suggest that this is mediated by on- and off-cells in the RVM.
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Comparative Study
Tissue monocytes/macrophages in inflammation: hyperalgesia versus opioid-mediated peripheral antinociception.
Opioid-containing leukocytes migrate to peripheral sites of inflammation. On exposure to stress, opioid peptides are released, bind to opioid receptors on peripheral sensory neurons, and induce endogenous antinociception. In later stages of Freund's complete adjuvant-induced local inflammation, monocytes/macrophages are a major opioid-containing leukocyte subpopulation, but these cells also produce proalgesic cytokines. In this study, the role of tissue monocytes/macrophages in hyperalgesia and in peripheral opioid-mediated antinociception was investigated. ⋯ Partial depletion of tissue monocytes/macrophages impairs peripheral endogenous opioid-mediated antinociception without affecting hyperalgesia.