Peripheral antinociceptive action of amitriptyline in the rat formalin test: involvement of adenosine

Citation
J. Sawynok et al., Peripheral antinociceptive action of amitriptyline in the rat formalin test: involvement of adenosine, PAIN, 80(1-2), 1999, pp. 45-55
Citations number
78
Categorie Soggetti
Neurology,"Neurosciences & Behavoir
Journal title
PAIN
ISSN journal
03043959 → ACNP
Volume
80
Issue
1-2
Year of publication
1999
Pages
45 - 55
Database
ISI
SICI code
0304-3959(199903)80:1-2<45:PAAOAI>2.0.ZU;2-5
Abstract
The present study determined (1) whether amitriptyline could produce a loca l antinociceptive action in the formalin test, (2) whether endogenous adeno sine was involved in this action, and (3) which other systems might contrib ute to such an action. Coadministration of amitriptyline 10-100 nmol with 2 .5% formalin produced a dose-related reduction in phase 1 (0-12 min) and ph ase 2 (16-60 min) flinching behaviours, as well as in phase 2 biting/lickin g time (no phase 1 expression). This action was not seen or only partially expressed at low concentrations of formalin (0.5%, 0.75%). Coadministration of caffeine with amitriptyline partially reversed the antinociceptive acti on of amitriptyline against both behaviours at 2.5% formalin. At 1.5% forma lin, caffeine still produced only a partial reversal of effect; this appear ed to be due to a block of adenosine A(l) receptors, as it was also seen wi th the selective adenosine A(l) receptor antagonist, 8-cyclopentyl-1,3-dime thylxanthine. Using antagonists for a number of other systems, no evidence for an involvement of alpha-adrenergic, histamine, excitatory amino acid or opioid receptors in the action of amitriptyline was observed or inferred. A local anaesthetic action for amitriptyline remains a possibility for the residual action. These results indicate that amitriptyline can produce a lo cal peripheral antinociceptive action which is mediated, in part, by an int eraction with endogenous adenosine, most likely an inhibition of the cellul ar uptake of adenosine with a consequent activation of adenosine Al recepto rs on sensory nerve terminals. Local application of amitriptyline by cream or gel might prove to be a useful method of drug delivery in inflammatory p ain states. (C) 1999 International Association for the Study of Pain. Publi shed by Elsevier Science B.V.