Articles: hyperalgesia.
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Opioids are frequently used for the treatment of moderate to severe acute and chronic pain. However, clinical evidence suggests that opioids can elicit increased sensitivity to noxious stimuli suggesting that administration of opioids can activate both, pain inhibitory and pain facilitatory systems. Acute receptor desensitization via uncoupling of the receptor from G proteins, upregulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA) receptor system and descending facilitation have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. ⋯ Brief exposures to mu-receptor agonists induce long-lasting hyperalgesic effects for days. Furthermore, the prolonged use of opioids in patients often requires increasing doses and may be accompanied by the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs such as NMDA antagonists, alpha(2)-agonists, or nonsteroidal anti-inflammatory drugs (NSAID), opioid rotation, or combinations of opioids with different receptor selectivity.
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The purpose of this review is to highlight the important recent advances in this fast developing field of pain mechanisms. It is now recognized that acute tissue and neural injuries can result in nociceptor sensitization (primary hyperalgesia) and spinal cord hyperexcitability or central sensitization that results in secondary hyperalgesia and allodynia. ⋯ The research of the last decade has focused on the biochemical and structural plasticity of the nervous system following tissue and nerve injury. The mechanisms involved in the transition from acute to chronic pain are complex with the involvement of interacting receptor systems and intracellular ion flux, second messenger systems, new synaptic connections and apoptosis.
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Comparative Study
GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin-induced prolonged noxious stimulation.
Gangliosides are a family of sialic acid-containing glycosphingolipids that are highly enriched in the mammalian nervous system. In particular, b- and c-series gangliosides, all of which contain alpha-2,8 sialic acids, have been considered to play important roles in adhesion, toxin-binding, neurite extension, cell growth and apoptosis. However, the neurobiological functions of these series of gangliosides remain largely unknown. ⋯ No significant differences in the conduction velocity of the sciatic nerve, and no apparent morphologic differences in the spinal cord and the sciatic nerve were detected between the wild-type and the mutant mice. These results suggested that b- and c-series gangliosides are critical in the development and/or maintenance of the sensory nervous system responsible for the transmission of acute pain sensation and pain modulation. Moreover, they play an important role in the development of hyperalgesia induced by inflammation.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Oct 2005
Corticotropin-releasing factor receptor 1 mediates acute and delayed stress-induced visceral hyperalgesia in maternally separated Long-Evans rats.
In rodents, maternal pup interactions play an important role in programming the stress responsiveness of the adult organism. The aims of this study were 1) to determine the effect of different neonatal rearing conditions on acute and delayed stress-induced visceral sensitivity as well as on other measures of stress sensitivity of the adult animal; and 2) to determine the role of corticotropin-releasing factor receptor (CRF-R) subtype 1 (CRF(1)R) in mediating visceral hypersensitivity. Three groups of male Long-Evans rat pups were used: separation from their dam for 180 min daily from postnatal days 2-14 (MS180), daily separation (handling) for 15 min (H), or no handling. ⋯ In MS rats, both CRF-R antagonists abolished acute and delayed increases in VMR. Rearing conditions have a significant effect on adult stress responsiveness including immediate and delayed visceral pain responses to an acute stressor. Both acute and delayed stress-induced visceral hypersensitivity in MS rats are mediated by the CRF/CRF(1)R system.
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Neuroscience letters · Sep 2005
Spinal glial glutamate transporters downregulate in rats with taxol-induced hyperalgesia.
Changes in the expression of glial glutamate transporters (GLAST and GLT-1) were examined in the spinal cord of rats with chemotherapy (taxol)-induced mechanical hyperalgesia. Immunohistochemical studies show that the expression of both GLAST and GLT-1 in the L4-L5 spinal dorsal horn is decreased by 24% (P<0.001) and 23% (P<0.001), respectively, in rats with taxol-induced hyperalgesia as compared with those in control rats. These changes were further confirmed using an enzyme-linked immunosorbent assay that confirmed downregulation of GLAST by 36% (P<0.05) and GLT-1 by 18% (P<0.05) in the L4-L5 spinal cord of taxol-treated rats. These data indicate that downregulation of glutamate transporters may contribute to the development of hyperalgesia induced by taxol and suggest that glutamate transporters may be a new target for treatment of pain.