SPONTANEOUS CHRONIC PAIN AFTER EXPERIMENTAL THORACTOMY REVEALED BY CONDITIONED PLACE PREFERENCE: morphine differentiates tactile evoked pain from spontaneous pain

摘要

Chronic pain following surgery limits social activity, interferes with work and causes emotional suffering. A major component of such pain is is reported as “resting” or spontaneous pain with no apparent external stimulus. Although experimental animal models can simulate the stimulus-evoked chronic pain that occurs after surgery, there have been no studies of spontaneous chronic pain in such models. Here the Conditioned Place Preference (CPP) paradigm was used to reveal resting pain after experimental thoracotomy. Male Sprague-Dawley rats received a thoracotomy with 1 hour rib retraction, resulting in evoked tactile hypersensitivity, previously shown to last for at least 9 weeks. Intraperitoneal injections of morphine (2.5 mg/kg) or gabapentin (40mg/kg) gave equivalent 2-3h long relief of tactile hypersensitivity, when tested 12-14 days post-operative. In separate experiments, single trial CPP was conducted 1 week before thoracotomy and then 12 days (gabapentin) or 14 days (morphine) after surgery, followed the next day by one conditioning sesssion with morphine or gabapentin, both vs saline. The gabapentin-conditioned, but not the morphine-conditioned rats showed a significant preference for the analgesia-paired chamber, despite the two agents’ equivalent effect in relieving tactile allodynia. These results show that experimental thoracotomy in rats causes spontaneous pain, and that some analgesics, such as morphine, that reduce evoked pain do not also relieve resting pain, suggesting that pathophysiological mechanisms differ between these two aspects of long-term post-operative pain.