The development of pain-related behaviour and opioid tolerance after neuropathy-inducing surgery and sham surgery

The inability of opioids to control pain over time may be influenced by dif ferent factors such as drug tolerance, hyperalgesia due to repeated morphin e administration or progression of the original disease. In addition, chron ic pain may alter morphine tolerance development. This study examined wheth er chronic morphine exposure differently affects mechanical and thermal sti mulus evoked pain-related behaviour in non-operated, nerve-injured and sham -operated rats. Further, we studied the effect of nerve injury and sham sur gery on the development of tolerance to the analgesic effect of morphine. V ocalization thresholds to paw pressure and struggle latencies to hindpaw im mersion into a 46 degreesC hot-water bath were determined in groups of non- operated rats, nerve-injured (chronic constriction of the sciatic nerve) an d sham-operated rats. Immediately thereafter, pretreatment regimens with s. c. injections of either saline or morphine (10 mg/kg) were started. Injecti ons were given twice daily on post-operative days 12-15, when the abnormal pain behaviour in nerve-injured rats is at a stable maximum. On day 16, the effect of an acute dose of i.v. morphine (1 mg/kg) was tested. On day 12 t he baseline vocalization threshold and struggle latency were decreased in n erve-injured but not in non- and sham-operated rats. Morphine pretreatment further decreased the vocalization threshold in nerve-injured rats and indu ced threshold reductions in non- and sham-operated rats. In the thermal tes t, morphine pretreatment produced no change in baseline latencies in any of the groups. Following morphine pretreatment, acute i.v. morphine on day 16 remained effective against both mechanical and thermal stimuli in non-oper ated rats, but was strongly reduced in nerve-injured rats. Sham-operated ra ts displayed a tendency towards a reduced effect of i.v. morphine after mor phine pretreatment in the mechanical but not in the thermal test. The resul ts suggest that mechanical afferent systems may be more sensitive to hypera lgesia associated with repetitive morphine injections than thermal systems and that nerve injury facilitates the development of tolerance to morphine analgesia. (C) 2000 International Association for the Study of Pain. Publis hed by Elsevier Science B.V. All rights reserved.