A study on the mechanisms involving the anti-inflammatory effect of amitriptyline in carrageenan-induced paw edema in rats.

Anti-inflammatory effects of antidepressants have been reported in some studies, but the mechanisms underlying these effects remain unknown. Amitriptyline, a tricyclic antidepressant, is widely used in the management of psychological disorders and various types of pain, including neuropathic pain or fibromyalgia. In our previous work, we found the role of supraspinal mechanisms in the anti-inflammatory effect of amitriptyline. In the line of the indicated study, we sought to evaluate the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) application of amitriptyline in the carrageenan-induced paw edema in rats in more details. Our findings confirmed that i.p. (40 and 80 mg/kg) and i.c.v. (100 μg/rat) injection of amitriptyline inhibited carrageenan-induced inflammation at different times. We also found that both i.p. and i.c.v. amitriptyline significantly decreased migration of polymorphonuclear (PMN) leucocytes into the site of inflammation, according to pathological evidence and the activity of myeloperoxidase (MPO). Furthermore, i.p. amitriptyline at the applied doses markedly reduced interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels in the paw treated with carrageenan. Our results also showed that i.c.v. amitriptyline noticeably decreased the concentration of IL-1β in the inflamed paws. The TNF-α levels reduced in the i.c.v. group, even though these reductions were not statistically significant. These results confirmed the anti-inflammatory effects of systemic and central amitriptyline in the carrageenan-induced paw edema in rats, and demonstrated that these effects mediated mostly through the inhibition of PMN cells migration and release of IL-1β and TNF-α into the site of inflammation.