Behavioural evidence for a bidirectional effect of systemic naloxone in a model of experimental neuropathy in the rat.
In animal models of inflammatory pain, we have demonstrated that the opioid antagonist naloxone induces a paradoxical analgesic effect at very low systemic doses, and a hyperalgesic effect at high doses. We have therefore proposed, that opioid systems are modified in these animals with persistent pain. The aim of the present study was to investigate the activity of naloxone through another model of pain in the rat due to a peripheral neuropathy of the sciatic nerve. The neuropathy was created by 4 ligatures around the sciatic nerve. We analyzed the effects of i.v. naloxone (3 and 10 micrograms/kg, 1 mg/kg) on the vocalization thresholds to paw pressure 8 days after the sciatic ligation. Three and 10 micrograms/kg naloxone produced a significant paradoxical antinociceptive effect on responses from the affected paw (with a mean increase of about 50 and 30% of the preinjection values, respectively) and also from the non-affected paw, although the effect was less potent. By contrast, 1 mg/kg naloxone elicited a significant hyperalgesia on responses from the affected and non-affected paw. The effects of the microdoses, but not those of the high dose, were clearly related to the vocalization thresholds measured for each rat just before injection. This study clearly shows that naloxone induces bidirectional effects in a rat model of neuropathic pain, which contradicts the current statement that neuropathic pain is opioid-resistant. The present results also suggest that these effects are not related to inflammatory processes, and may be due to modifications of opioid systems in these animals with persistent pain.
Unite de Recherche de Physiopharmacologie du Systeme Nerveux, U161, I.N.S.E.R.M., Paris, France.
N
N
Attal
V
V
Kayser
F
F
Jazat
G
G
Guilbaud
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D009270:Naloxone / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000503:physiopathology*; D012684:Sensory Thresholds / Q000187:drug effects*
D009270:Naloxone