Enhancement of antinociceptive effect by co-administration of amitriptyline and crocus sativus in a rat model of neuropathic pain

ABSTRACT

The aim of this study was to evaluate the anti-nociceptive effects of a low, sub-effective dose of amitriptyline, in combination with the different doses of ethanolic and aqueous extracts of Crocus sativus following sciatic nerve chronic constriction injury [CCI] in rats. Amitriptyline [3, 10 and 30 mg/Kg, i.p.] and the extracts [25, 50 and 100 mg/Kg, i.p.], were separately administered at the time of CCI for 7 consecutive days. In combination therapy, the sub-antinociceptive dose of amitriptyline [3 mg/Kg] was given with the three different doses of extracts for seven days. Mechanical allodynia, thermal allodynia and thermal hyperalgesia were evaluated by von Frey, acetone and radiant heat tests, respectively, 1 day before and on days 3, 5 and 7 after surgery. Co-administration of amitriptyline [3 mg/Kg] with aqueous extract [50, 100 mg/Kg,] produced more potent cold anti-allodynic [P < 0.01 and P < 0.001, respectively] as well as thermal anti-hyperalgesic [P < 0.05] effects than that produced by each of them. Amitriptyline [3 mg/Kg] plus ethanolic extract [50, 100 mg/Kg] produced more potent cold anti-allodynic [P < 0.05 and P < 0.001, respectively] as well as thermal anti-hyperalgesic [P < 0.05] effects as compared with the sum effects produced by each of them. Mechanical anti-allodynia effect was only potentiated with the co-administration of amitriptyline with the high dose of aqueous extract [100 mg/Kg, P < 0.001]. Our study supports the use of saffron as an adjunctive to amitriptyline to improve the therapeutic outcome in the management of neuropathic pain