Attenuation of formalin pain responses in the rat by adrenal medullary transplants in the spinal subarachnoid space.

Previous reports have indicated that the implantation of adrenal medullary chromaffin cells into the spinal subarachnoid space can reduce both acute and chronic pain in several animal models. Recent findings suggest that acute and chronic pain alleviation may be mediated by distinct mechanisms. Since the formalin response is composed of an acute and tonic phase which can be pharmacologically distinguished, the ability of adrenal medullary implants to alter these responses was assessed. In rats with adrenal medullary transplants, both phases of the formalin response were attenuated, in contrast to control implanted animals. Suppression of the acute phase by adrenal medullary implants was reversed by the opiate antagonist naloxone, and partially reversed by the alpha-adrenergic antagonist phentolamine, suggesting that opioid peptides and catecholamines released by the implanted chromaffin cells contribute to the observed antinociception. However, neither antagonist altered the antinociceptive effects of adrenal medullary implants on the tonic phase of the formalin response. These results indicate that adrenal medullary implants in the spinal subarachnoid space alleviate acute and tonic pain via distinct pharmacologic mechanisms.