Acute amitriptyline in a rat model of neuropathic pain: differential symptom and route effects

The present study was designed to determine whether amitriptyline, a protot ypical tricyclic antidepressant, could produce pain relieving properties in a rat model of neuropathic pain. Nerve injury was produced by tight ligati on of the lumbar 5th and 6th dorsal roots and this resulted in persistent s timulus evoked neuropathic pain symptoms (tactile allodynia and thermal hyp eralgesia). Thermal hyperalgesia was measured using a focused light beam di rected at the ventral surface of the paw while tactile allodynia was determ ined using Semmes-Weinstein monofilaments applied to the ventral surface of the paw. Amitriptyline was administered systemically (intraperitoneal), sp inally (intrathecal cannula), and locally (subcutaneously) via direct injec tion into the dorsal surface of the paw. Following systemic administration, amibriptyline completely reversed thermal hyperalgesia (10 mg/kg) in the i njured paw. Spinal administration of amitriptyline (60 mu g) also produced an antihyperalgesic effect. Interestingly, local administration of amitript yline (100 nmol) had an immediate antihyperalgesic effect that persisted fo r 120 min following administration. Amitriptyline had no alleviating effect against mechanical allodynia regardless of the route of administration, bu t curiously, produced hyperaesthesia in the contralateral paw. These result s indicate that in the rat model of spinal nerve ligation, amitriptyline is effective in alleviating thermal hyperalgesia (systemically, spinally and locally) but is ineffective against mechanical allodynia. The peripheral ef ficacy of amitriptyline suggests the possibility of the development of crea m formulations that may be able to increase the local concentration of amit riptyline without increasing the systemic dose and the subsequent occurrenc e of side effects. (C) 1999 International Association for the Study of Pain . Published by Elsevier Science B.V.