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.


CONCLUSIONS
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.
Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Valiollah
V
Hajhashemi
Hossein
H
Sadeghi
Mohsen
M
Minaiyan
Ahmad
A
Movahedian
Ardeshir
A
Talebi
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage*; D000639:Amitriptyline / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D058668:Adrenergic alpha-1 Receptor Antagonists; D000893:Anti-Inflammatory Agents; D000639:Amitriptyline; D002351:Carrageenan
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