The differential effects of morphine and the alpha 2-adrenoceptor agonists clonidine and dexmedetomidine on the prevention and treatment of experimental neuropathic pain

Abstract

The effect of intrathecal morphine (MO) and the alpha 2-adrenoceptor agonists clonidine (CLON) and dexmedetomidine on self-mutilation (autotomy), a behavior that may indicate the presence of neuropathic pain, has been examined in rats. In one experiment, a single dose of MO (50 micrograms), but not CLON (50 micrograms) or saline (SAL), injected 60 min before unilateral sciatic nerve section caused a significant decrease in autotomy during the 28-day observation period. In a second experiment, the same dose of MO administered 15 min after nerve section had no beneficial effect on autotomy compared to CLON or SAL. In a third experiment, MO (10 micrograms), CLON (10 micrograms), and dexmedetomidine (1 microgram), an alpha 2-agonist with higher affinity for the alpha 2-receptor than CLON, or SAL were injected intrathecally twice daily for 21 days starting 24 h after axotomy. The rats administered CLON or dexmedetomidine autotomized significantly less than those receiving MO or SAL at 14 days and 21 days after nerve section. Thus, MO, but not alpha 2-agonists, is beneficial in preventing autotomy, a possible sign of neuropathic pain after nerve injury, whereas alpha 2-agonists, but not opioids, are useful in treating such pain chronically.