Subcutaneous administration of
haloperidol or its metabolites I or II (
reduced haloperidol) dose-dependently reversed
capsaicin-induced (1 microg, intraplantar) mechanical
hypersensitivity of the hind paw (stimulated with a nonpainful, 0.5-g force, punctate stimulus). The order of potency of these drugs to induce antiallodynic effects was the order of their affinity for brain sigma-1 (sigma(1)) receptor ([(3)H](+)-
pentazocine-labeled). Antiallodynic activity of
haloperidol and its metabolites was dose-dependently prevented by the selective sigma(1) receptor agonist
PRE-084, but not by
naloxone. These results suggest the involvement of sigma(1) receptors, but discard any role of the endogenous
opioid system, on the antiallodynic effects.
Dopamine receptor antagonism also appears unlikely to be involved in these effects, since the D(2)/D(3) receptor antagonist (-)-
sulpiride, which had no affinity for sigma(1) receptors, showed no antiallodynic effect. None of these drugs modified hind-paw withdrawal after a painful (4 g force) punctate mechanical stimulus in noncapsaicin-sensitized animals. As expected, the control drug
gabapentin showed antiallodynic but not antinociceptive activity, whereas
clonidine exhibited both activities and
rofecoxib, used as negative control, showed neither.
CONCLUSION: