Isobolographic analysis of interaction between intrathecal morphine and clonidine in the formalin test in rats.
The formalin test, an experimental model of injury-induced central sensitisation, was used. The antinociceptive interaction between intrathecal morphine and clonidine was evaluated based on the inhibition of the phase 1 and 2 of the formalin response, induced by both drugs, given alone or in combinations with fixed dose ratios. Morphine and clonidine, at doses not affecting motor performance, produced dose-dependent inhibition in the formalin test, with similar ID50 values in phase 1 and 2; 0.66 and 0.45 nmol and 4.1 and 3.5 nmol, respectively. Isobolographic analysis revealed a significant synergy. The combination ID50 was found to be significantly lower than the respective theoretical additive ID50 for both fixed dose ratios (1:3 and 1:10) in both phases of the formalin test. The similar total dose fraction of the additive ID50 in phase 1 and 2 indicates the same magnitude of synergy and may suggest that the mechanisms of the spinal clonidine-morphine synergy do not differ significantly between both phases of the formalin test.
Przesmycki
K
K
Department of Anaesthesiology and Intensive Therapy, Medical University School, Lublin, Poland.
Dzieciuch
J A
JA
Czuczwar
S J
SJ
Kleinrok
Z
Z
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005557:Formaldehyde; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D005557:Formaldehyde; D009020:Morphine; D003000:Clonidine