Synergistic antinociceptive effect of amitriptyline and morphine in the rat orofacial formalin test.
BACKGROUND
Combination therapy is often used to increase the clinical utility of analgesic agents. The coadministration of two compounds may achieve analgesia at doses lower than those required for either compound alone, leading to enhanced pain relief and reduction of adverse effects. Herein, the authors describe the effect of coadministration of morphine and amitriptyline on cutaneous orofacial inflammatory pain in rats.


METHODS
Amitriptyline, morphine, or the combination of amitriptyline and morphine was administered systemically to rats, and antinociceptive effects were determined by means of the rat orofacial formalin test. Isobolographic analysis was used to define the nature of the interactions between morphine and amitriptyline.


RESULTS
Amitriptyline as well as morphine produced a dose-related inhibition in the first phase and the second phase of rubbing activity. ED50 values against rubbing behavior were 14.6 mg/kg (95% confidence interval, 10.2-33.5 mg/kg) and 1.3 mg/kg (95% confidence interval, 1.0-1.7 mg/kg) for amitriptyline and morphine, respectively. Combinations of increasing fractional increments of amitriptyline and morphine ED50 doses produced a synergistic effect against rubbing behavior, as revealed by isobolographic analysis.


CONCLUSIONS
The current study suggests that systemic amitriptyline and morphine synergistically inhibit cutaneous orofacial inflammatory pain in rats.
Luccarini
Philippe
P
Institut Universitaire de Technologie Génie Biologique, Universié d' Auvergne-Clermont I, Les Cézeaux, Aubière, France.
Perrier
Laurent
L
Dégoulange
Céline
C
Gaydier
Anne-Marie
AM
Dallel
Radhouane
R
D000639:Amitriptyline / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005157:Facial Pain / Q000188:drug therapy*; D005557:Formaldehyde; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D000701:Analgesics, Opioid; D000928:Antidepressive Agents; D000639:Amitriptyline; D005557:Formaldehyde; D009020:Morphine