The role of central mechanisms in the anti-inflammatory effect of amitriptyline on carrageenan-induced paw edema in rats

OBJECTIVE The present study was designed to further investigate the effect of amitriptyline, a classical tricyclic antidepressant, on carrageenan-induced paw edema in rats. METHODS First, amitriptyline was administered intraperitoneally (i.p.) at doses of 20, 40 and 80 mg kg-1, 30 min before subplantar injection of carrageenan. Second, amitriptyline was given intracerebroventriculary or intrathecally at doses of 25, 50 and 100 μg/rat, 30 min prior to carrageenan challenge. Third, the effect of adrenergic receptor antagonists such as propranolol (10 mg kg-1, i.p.), prazosin (4 mg kg-1, i.p.) and yohimbine (10 mg kg-1, i.p.) and an opioid receptor antagonist (naloxone, 4 mg kg-1, i.p.) on the anti-inflammatory effect of amitriptyline (40 mg kg-1, i.p.) was investigated. RESULTS Our data confirm that intraperitoneally administered amitriptyline exhibits a marked anti-inflammatory effect on carrageenan-induced paw edema in rats 4 h postcarrageenan challenge (P < 0.001). Intracerebroventricular (i.c.v.) administration of amitriptyline also reduced the development of paw edema at 4 h postcarrageenan (P < 0.001), but intrathecal (i.t.) application of amitriptyline failed to alter the degree of paw swelling. Furthermore, the applied antagonists did not modify the anti-inflammatory effect of amitriptyline. CONCLUSION These results support the view that amitriptyline has a considerable anti-inflammatory effect on carrageenan-induced paw edema in rats and suggest that at least a part of this property could be mediated through supraspinal sites. Moreover, it seems unlikely that the investigated adrenergic and opioid receptors have a significant role in this effect of amitriptyline.