SUBCUTANEOUS FORMALIN PRODUCES CENTRIFUGAL HYPERALGESIA AT A NON-INJECTED SITE VIA THE NMDA NITRIC-OXIDE CASCADE

Previous work has demonstrated that pain facilitation can occur follow ing injection of subcutaneous irritants, such as formalin. Such studie s have focused on apparent pain facilitation induced at the site of ir ritant injection. Changes in processing of incoming pain information h ave typically been assumed to result from activation of neurocircuitry intrinsic to the spinal cord. The present series of studies have exam ined hyperalgesia exhibited at a site distant from the site of irritan t injection and have begun to define the neurocircuitry and neuropharm acology underlying this pain enhancement. This work demonstrates that s.c. formalin injected into the dorsum of one hindpaw in rats produces prolonged hyperalgesia as measured by the tailflick test. Hyperalgesi a is not mediated solely by circuitry intrinsic to the spinal cord, bu t rather involves activation of centrifugal pathways originating withi n the brain and descending to the spinal cord via pathway(s) outside o f the dorsolateral funiculus. At the level of the spinal cord, this hy peralgesic state is mediated by an NMDA-nitric oxide cascade, since hy peralgesia can be abolished by administration of either an NMDA antago nist (APV) or a nitric oxide synthesis inhibitor (L-NAME).