Tramadol is more effective than morphine and amitriptyline against ischaemic pain but not thermal pain in rats

The aim of this study was to compare the analgesic efficacies of tramadol, which acts on opioid receptors and inhibits monoamine reuptake, to amitriptyline, a monoamine reuptake inhibitor as well as to morphine, an opioid receptor agonist. We compared the motor function impairment and response latencies to noxious thermal and noxious ischaernic challenges after tramadol administration to those after morphine and after amitriptyline administration. We injected Sprague-Dawley rats (i.p.) with either tramadol (1, 5, 15 and 25 mg kg(-1)), morphine (0.0 1, 0. 1, 1 and 5 mg kg(-1)) or amitriptyline (1, 3 and 10 mg kg(-1)) and a control injection of saline (100 [il). We measured the tail flick latency to a noxious thermal challenge after tail immersion in a 49 degrees C water bath and response latency to noxious ischaemia, induced by a tourniquet inflated at the base of the tail, was recorded as ischaemic escape latency. In a separate group of rats, we assessed motor function by placing the rats on a rotarod, rotating at 25 rpm, for a maximum of 30 min after drug administration. We recorded the time to the rat's third fall from the rotarod. Tramadol (15 mg kg(-1)) produced a 107% increase in response latency from pre-injection value as did 25 mg kg(-1) tramadol (79%), 1 mg kg(-1) morphine (85%), 5 mg kg(-1) morphine (138%) and 10 mg kg(-1) amitriptyline (46%) against a noxious thermal challenge. The escape latency against noxious ischaemia after morphine and amitriptyline administration did not change, despite an increase in dose, while increasing doses of tramadol (1-25 mg kg(-1)) provided increasing analgesia against noxious ischaemia. Significant impairment to motor function occurred after morphine (5 mg ka(-1)), tramadol (15 mg kg(-1)) and amitriptyline (10mg kg(-1)) administration, with only 11, 50 and 38% of animals, respectively, completing the rotarod trial, compared to 100% completion after saline administration. As previously demonstrated, morphine was more potent than tramadol for the relief of thermal pain but tramadol may be a more beneficial drug for relieving severe ischaemic pain. (C) 2007 Elsevier Ltd. All rights reserved.