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 different factors such as drug tolerance, hyperalgesia due to repeated morphine administration or progression of the original disease. In addition, chronic pain may alter morphine tolerance development. This study examined whether chronic morphine exposure differently affects mechanical and thermal stimulus evoked pain-related behaviour in non-operated, nerve-injured and sham-operated rats. Further, we studied the effect of nerve injury and sham surgery on the development of tolerance to the analgesic effect of morphine. Vocalization thresholds to paw pressure and struggle latencies to hindpaw immersion into a 46 degrees C hot-water bath were determined in groups of non-operated rats, nerve-injured (chronic constriction of the sciatic nerve) and sham-operated rats. Immediately thereafter, pretreatment regimens with s.c. injections of either saline or morphine (10 mg/kg) were started. Injections 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 the baseline vocalization threshold and struggle latency were decreased in nerve-injured but not in non- and sham-operated rats. Morphine pretreatment further decreased the vocalization threshold in nerve-injured rats and induced threshold reductions in non- and sham-operated rats. In the thermal test, 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-operated rats, but was strongly reduced in nerve-injured rats. Sham-operated rats displayed a tendency towards a reduced effect of i.v. morphine after morphine pretreatment in the mechanical but not in the thermal test. The results suggest that mechanical afferent systems may be more sensitive to hyperalgesia associated with repetitive morphine injections than thermal systems and that nerve injury facilitates the development of tolerance to morphine analgesia.