The bidirectional dose-dependent effect of systemic naloxone is also related to the intensity and duration of pain-related disorders: a study in a rat model of peripheral mononeuropathy.
In an experimental model of mononeuropathy in the rat, created by 4 ligatures around the sciatic nerve, i.v. naloxone 1 week after surgery induces bidirectional effects (antinociceptive effects at very low doses, hyperalgesic effects with high doses). Using the same nociceptive test (vocalization thresholds to paw pressure), the activity of the same doses of naloxone (3 micrograms/kg, and 1 mg/kg) was investigated 2 weeks after sciatic ligation, when the behavioural pain-related disorders are at a maximum. Three micrograms/kg naloxone produced a significant antinociceptive effect on the lesioned and non-lesioned paw, which was clearly related to the degree as well as to the duration of pain-related signs in the rat. By contrast, the high dose of naloxone did not induce a mean significant effect when tested on either paw; however, it elicited a potent hyperalgesic effect in those rats which had recovered from hyperalgesia at this 2 week time point after the sciatic injury.
Attal
N
N
INSERM U 161, Paris, France.
Kayser
V
V
Guilbaud
G
G
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D009270:Naloxone / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D014828:Vocalization, Animal / Q000187:drug effects
D009270:Naloxone