ANTI-ALLODYNIC ACTIONS OF INTRAVENOUS OPIOIDS IN THE NERVE INJURED RAT - POTENTIAL UTILITY OF HEROIN AND DIHYDROETORPHINE AGAINST NEUROPATHIC PAIN

Neuropathic pain has been suggested to be resistant to treatment with opiates. Such perceived lack of opioid responsiveness may be due to th e dose-range over which specific opioid compounds have been studied as well as the efficacy of these compounds. Dihydroetorphine is a novel opiate that demonstrates significantly greater analgesic potency compa red to morphine, and which also demonstrates diminished capacity for p roducing physical dependence in laboratory animals. The present study compared the intravenous (i.v.) efficacy, potency and duration of acti on of dihydroetorphine, fentanyl, heroin and morphine in producing ant i-allodynic actions in a rat model of neuropathic pain (ligation of th e L5/L6 nerve roots). AU compounds produced significant anti-allodynic activity with dihydroetorphine being the most potent (A(50) of 0.2 mu g kg(-1), i.v.). Morphine was approximately 7440 times less potent th an dihydroetorphine while heroin and fentanyl were approximately 163.5 and 6.9 times less potent in producing anti-allodynic actions. Dihydr oetorphine also showed a maximal effect at 0.6 mu g kg(-1) in all anim als tested, while 100 mu g kg(-1) was required for heroin to produce a maximal effect. Fentanyl and morphine did not elicit a maximum anti-a llodynic response (74 and 76% maximum possible effect (%MPE), respecti vely). As expected, fentanyl showed a relatively brief duration of act ion (approximately 20 min at the highest tested dose), while dihydroet orphine and morphine demonstrated anti-allodynic actions for up to 45 min. Heroin had the longest duration of action, producing significant anti-allodynic effects for up to 90 min. These data show that dihydroe torphine and heroin produce potent and long-lasting anti-allodynic act ions in this model. Additionally, in contrast to morphine and fentanyl , both dihydroetorphine and heroin were able to achieve a maximal resp onse. The remarkable potency, maximal efficacy and duration of action of these compounds, particularly dihydroetorphine, suggests that these compounds may warrant further examination as potential therapeutic tr eatments for neuropathic pain states. (C) 1998 Elsevier Science B.V. A ll rights reserved.