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.