Peripherally administered amitriptyline derivatives have differential anti-allodynic effects in a rat model of neuropathic pain.

We assessed if derivatives of amitriptyline could alleviate mechanical allodynia in a rat model of neuropathic pain. N-methyl amitriptyline (NMA), and amitriptyline HCl (AHC) were compared to evaluate the antiallodynic effects produced by systemic and peripheral administration. Under general anesthesia with halothane, neuropathic injury was produced in rats by tightly ligating the left L5 and L6 spinal nerves. All animals developed neuropathic pain behaviors within 7 days after the surgery. For systemic delivery, three groups of rats were injected intraperitoneally with NMA (15 mg/kg), AHC (12.5 mg/kg), or saline. For peripheral routes of injection, rats were divided into 3 x 3 groups and injected with 100, 330, and 1000 nmol/kg doses of each NMA, AHC and 0.9% normal saline. NMA and AHC suppressed mechanical allodynia following peripheral administration but not following intraperitoneal injection. NMA was less potent but showed a longer-acting response than AHC. This study shows that NMA can be used to relieve mechanical allodynia and is a longer-acting agent than AHC.