Pain
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Melatonin, its agonists/antagonists were administered intrathecally (i.t.) before/after intradermal injection of capsaicin. Capsaicin produced an increase in the paw withdrawal frequency (PWF) in the presumed area of secondary mechanical allodynia and hyperalgesia. Melatonin agonists in the absence of a capsaicin injection decreased the PWF significantly, whereas melatonin antagonists given intrathecally alone were ineffective in the absence of a capsaicin injection. ⋯ In spinal rats, the data showed comparable effects of melatonin analogs on capsaicin-induced secondary mechanical hyperalgesia. Animal motor function tested by 'activity box' showed that motion activity was not affected by i.t. melatonin or its antagonist. These results suggest that activation of the endogenous melatonin system in the spinal cord can reduce the generation, development and maintenance of central sensitization, with a resultant inhibition of capsaicin-induced secondary mechanical allodynia and hyperalgesia.
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The present study investigated whether mechanical allodynia following contusive spinal cord injury (SCI) of the thoracic segments 12 and 13 of the rat was associated with a reduction in gamma-aminobutyric acid (GABA)ergic inhibition adjacent to the site of injury. Five to 7 days following SCI, extracellular recordings were obtained from dorsal horn neurones located 1-2 segments caudal to the injury, in non-allodynic and allodynic halothane anaesthetised rats and from comparable neurones in normal rats. To assess spinal GABAergic inhibition in the three groups of animals, spontaneous and evoked cell firing rates were recorded before, during and after microiontophoretic application of the GABA(A) receptor antagonist bicuculline. ⋯ In non-allodynic SCI animals, bicuculline ejection led to significant changes in receptive field size, paired-pulse depression and responses to brush and pinch stimulation that were comparable to those observed in normal animals. By contrast, in allodynic SCI animals, bicuculline ejection had little or no effect on dorsal horn neurone responses to mechanical skin stimuli and paired-pulse depression despite reliably blocking the inhibition of cell firing produced by similarly applied GABA. The demonstration of reduced GABAergic inhibition predominantly in the allodynic SCI rats suggests that such a deficiency contributed to this pain-related behaviour acutely following SCI.
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Comparative Study
Stimulus-dependent specificity for annexin 1 inhibition of the inflammatory nociceptive response: the involvement of the receptor for formylated peptides.
In this study we investigated how the peptides derived from the glucocorticoid-inducible protein annexin 1 are able to alter the nociceptive threshold of mice. The effects of the annexin1 fragment 2-26 (Anxa1(2-26)) on nociceptive threshold were studied using both chemical (formalin test) and thermal (hot plate and tail flick test) nociceptive stimuli on mice. Subcutaneous administration of Anxa1(2-26) into the dorsal surface of the mouse's hind paw was able to selectively reduce formalin-induced nociceptive behavior in the last phase of the test. ⋯ We found that the formyl peptide receptor agonist formyl-MLF (fMLF) induced anti-nociceptive effects in the formalin test both after the peripheral and central administration. The formyl peptide receptor antagonist N-t-butoxycarbonyl-MLP did not alter the response to formalin, but it was able to block the anti-nociceptive effects of Anxa1(2-26,) Anxa1(2-12) and fMLF after peripheral or central administration. These results indicate that exogenously administered Anxa1 can peripherally and centrally inhibit the nociceptive transmission associated with inflammatory processes through a mechanism that involves formyl peptide receptors.