Intrathecally administered cholera toxin blocks allodynia and hyperalgesia in persistent pain models.

In persistent pain, the spinal cord concentration of the opioid peptide dynorphin increases dramatically, yet the function of dynorphin remains unknown. If prodynorphin expression could be manipulated in vivo, it might be possible to determine what role dynorphin plays in persistent pain. Previous work in our laboratory showed that prodynorphin expression is regulated through the cyclic adenosine monophosphate pathway. Therefore, we attempted to enhance prodynorphin expression in the spinal cord of rats by stimulating adenylate cyclase with cholera toxin; however, contrary to our hypothesis, intrathecally administered cholera toxin did not enhance prodynorphin expression. Rather, cholera toxin suppressed the increase in prodynorphin produced by inflammation. Cholera toxin also inhibited the allodynia and hyperalgesia associated with inflammation and nerve injury. Interestingly, the antiallodynic and antihyperalgesic actions of cholera toxin were reversed with the opioid receptor antagonist, naloxone. These findings suggest that cholera toxin enhances or unmasks an endogenous opioid pathway to produce its antiallodynic and antihyperalgesic effects. Furthermore, these data indicate that the suppression of the inflammation-induced increase in spinal cord prodynorphin is caused by the opioid-mediated decrease in the nociceptive stimulus.