Spinal sensitization mechanism in vincristine-induced hyperalgesia in mice.

Our aim was to investigate the possible involvement of spinal voltage-dependent Ca(2+) channels (VDCCs) in vincristine-induced hyperalgesia and also to characterize this hyperalgesic state in the spinal cord. Mice receiving vincristine displayed significantly lower mechanical nociceptive thresholds than controls. Intrathecal omega-conotoxin GVIA (an N-type blocker) produced dose-dependent inhibition of the mechanical nociception, its antinociceptive effect being greater in vincristine-treated mice than in controls. The antinociception of omega-agatoxin IVA (a P/Q-type blocker) and calciseptine (an L-type blocker) were both slightly, but not significantly greater in vincristine-treated mice. An N-methyl-D-aspartate-receptor antagonist but not a tachykinin-NK1-receptor antagonist produced greater antinociception in vincristine-treated mice. These results suggest that vincristine-induced hyperalgesia involves a sensitization of the spinal processing of mechanical sensory information via a mechanism involving N-type but not P/Q- or L-type VDCCs. A spinal glutamatergic pathway also appears to be involved in this hyperalgesia.