Articles: hyperalgesia.
-
The effects of BK agonists and antagonists, and other hyperalgesic/antihyperalgesic drugs were measured (3 h after injection of hyperalgesic drugs) in a model of mechanical hyperalgesia (the end-point of which was indicated by a brief apnoea, the retraction of the head and forepaws, and muscular tremor). DALBK inhibited responses to carrageenin, bradykinin, DABK, and kallidin. Responses to kallidin and DABK were inhibited by indomethacin or atenolol and abolished by the combination of indomethacin + atenolol. ⋯ The hyperalgesic response to LPS (1 microg) was inhibited by DALBK or HOE 140 and abolished by DALBK + HOE 140. The hyperalgesic response to LPS (5 microg) was not antagonized by DALBK + HOE 140. These data suggest: (a) a predominant role for B2 receptors in mediating hyperalgesic responses to BK and to drugs that stimulate BK release, and (b) activation of the hyperalgesic cytokine cascade independently of both B1 and B2 receptors if the hyperalgesic stimulus is of sufficient magnitude.
-
Anesthesia and analgesia · Jan 1999
Randomized Controlled Trial Clinical TrialPeripheral antihyperalgesic effect of morphine to heat, but not mechanical, stimulation in healthy volunteers after ultraviolet-B irradiation.
The objective of this study was to evaluate direct peripheral analgesic effects of morphine using a peripheral model of hyperalgesia and the technique of IV regional anesthesia (IVRA), thus allowing the differentiation between central and peripheral mechanisms of action. Two spots on the ventral sides of both forearms in 12 volunteers were irradiated with ultraviolet (UV)-B to induce thermal and mechanical hyperalgesia. One day after the induction of the inflammatory reaction, 40 mL of morphine hydrochloride 0.01% was administered via IVRA. Calibrated heat and phasic mechanical stimuli were applied to differentially determine impairments of tactile and nociceptive perception. Touch and phasic mechanical stimuli of noxious intensity to normal skin did not reveal altered responsiveness caused by morphine. In contrast, the administration of morphine significantly increased heat pain thresholds in the UV-B-pretreated skin areas. The peripheral antihyperalgesic effects of morphine were demonstrated only in inflamed skin areas. Direct central analgesic effects were ruled out by the lack of measurable plasma concentrations of morphine and its metabolites. Morphine 0.01% significantly diminished thermal, but not mechanical, hyperalgesia by a peripheral mode of action, which suggests inhibition of effector pathways leading to heat, but not mechanical, sensitization. ⋯ The peripheral analgesic effects of morphine were studied using modified IV regional anesthesia. When administered 1 day after the induction of dermal inflammation, morphine 0.01% diminished heat, but not primary mechanical, hyperalgesia. Therefore, suppression of mechanical hyperalgesia seen in previous studies could be predominantly due to inhibition of secondary (central) mechanical hyperalgesia.
-
Preclinical and clinical evidence indicates that locally administered opioid agonists produce an antihyperalgesic effect through peripheral opioid receptors in inflamed tissue. Loperamide, a mu opioid agonist, does not cross the blood-brain barrier and therefore lacks central effects after systemic administration. The authors defined the effects of topical loperamide on a thermal injury-induced hyperalgesia. ⋯ Loperamide, a peripherally acting mu opioid agonist, applied topically at the site of inflammation possesses a significant antihyperalgesic action without any systemic side effects.
-
Inflammation and hyperalgesia induce a dramatic up-regulation of opioid messenger RNA and peptide levels in nociceptive neurons of the spinal dorsal horn. Descending axons modulate nociceptive transmission at the spinal level during inflammatory pain, and may play a role in the development of persistent pain. The role of descending bulbospinal pathways in opioid-containing nociceptive neurons was examined. ⋯ These data suggest that increased dynorphin messenger RNA ipsilateral to inflammation, in rats without descending axons, was due to increased expression within the same cells and not to recruitment of additional dynorphin-expressing cells. This reflects a greater dynamic response of nociceptive neurons to noxious stimuli in the absence of descending modulation. Therefore, the net effect of descending afferents on spinal nociceptive circuits may be to reduce the response of opioid-containing neurons to noxious stimulation from the periphery.
-
Opioids and receptor antagonists of excitatory amino acids attenuate mechanical allodynia and thermal hyperalgesia in animal models of neuropathic pain. Recently, a kainate receptor antagonist, 2S,4R-4-methylglutamate, has been developed but has not been tested for antinociceptive effects in animal models of neuropathic pain. We evaluated whether 2S,4R-4-methylglutamate attenuated responses to mechanical and thermal stimuli in uninjured (control) rats and increased responsiveness in rats with chronic constriction injury. ⋯ At four to eight days following chronic constriction injury, animals that displayed increased responsiveness to mechanical and thermal stimuli were injected intraperitoneally with either dizocilpine maleate (0.1 mg/kg), morphine (4 mg/kg), vehicle as controls, or 2S,4R-4-methylglutamate (25, 50, 75 or 100 mg/kg). 2S,4R-4-Methylglutamate (25, 50, 75 and 100 mg/kg) significantly attenuated the frequency of responses to mechanical stimuli (Wilcoxon, P < 0.05) and the latency of responses to thermal stimuli (analysis of variance and Duncan's, P < 0.05). Dizocilpine maleate and morphine, as expected, also reduced these responses. These results suggest that, in addition to opioid and N-methyl-D-aspartate receptors, kainate receptors may play a role in the maintenance of mechanical allodynia and thermal hyperalgesia associated with peripheral nerve injury.