Delayed sympathectomy after a prolonged hyperalgesia results in a subsequent enhanced acute hyperalgesic response

We report on the ability of a delayed sympathectomy after a prolonged hyperalgesia to result in a subsequent enhanced hyperalgesic response. Sympathectomy was performed one day after injection of prostaglandin E2 plus rolipram, which induces a prolonged sympathetically-maintained hyperalgesia [Aley K. O. and Levine J. D. (1995) Eur. J. Pharmac. 273, 107-112]. The duration of hyperalgesia produced by a subsequent injection of prostaglandin E2 or prostaglandin E2 plus rolipram was then assessed. Lumbar surgical sympathectomy, done on day 2 or 3, prevented prostaglandin E2 plus rolipram-induced prolonged hyperalgesia from developing when they were injected five days after surgery, similar to the previous report of the effect of prior sympathectomy to block the rolipram enhancement [Aley K. O. and Levine J. D. (1995) Eur. J. Pharmac. 273, 107-112]. Sympathectomy done five days after injection of prostaglandin E2 plus rolipram, however, paradoxically prolonged (at least 10 days) hyperalgesia induced by a subsequent prostaglandin E2 plus rolipram injection, a duration much greater than that seen after prostaglandin E2 plus rolipram in naive animals. To determine the roles of prostaglandin E2 and rolipram in the prolongation of hyperalgesic response after delayed sympathectomy, rats were treated with either prostaglandin E2 or rolipram prior to sympathectomy. Prostaglandin E2 or rolipram alone were also administered five days after the sympathectomy. It was found that sympathectomy done five days after first injecting either prostaglandin E2 or rolipram alone did not produce enhanced hyperalgesic response. These data suggest that induction of a prolonged state of mechanical hyperalgesia causes time-dependent alterations in the sympathetic control of peripheral nociceptive mechanisms such that sympathectomy can lead to enhanced hyperalgesic response. These findings may be relevant to post-sympathectomy pain, a clinical entity for which there has been no available animal models.