Intrathecally administered cholera toxin blocks allodynia and hyperalgesiain persistent pain models

In persistent pain, the spinal cord concentration of the opioid peptide dyn orphin increases dramatically, yet the function of dynorphin remains unknow n. If prodynorphin expression could be manipulated in vivo, it might be pos sible to determine what role dynorphin plays in persistent pain. Previous w ork in our laboratory showed that prodynorphin expression is regulated thro ugh the cyclic adenosine monophosphate pathway. Therefore, we attempted to enhance prodynorphin expression in the spinal cord of rats by stimulating a denylate cyclase with cholera toxin; however, contrary to our hypothesis, i ntrathecally administered cholera toxin did not enhance prodynorphin expres sion. Rather, cholera toxin suppressed the increase in prodynorphin produce d by inflammation. Cholera toxin also inhibited the allodynia and hyperalge sia associated with inflammation and nerve injury. Interestingly, the antia llodynic and antihyperalgesic actions of cholera toxin were reversed with t he opioid receptor antagonist, naloxone. These findings suggest that choler a toxin enhances or unmasks an endogenous opioid pathway to produce its ant iallodynic and antihyperalgesic effects. Furthermore, these data indicate t hat the suppression of the inflammation-induced increase in spinal cord pro dynorphin is caused by the opioid-mediated decrease in the nociceptive stim ulus.