Antinociceptive Effects of Tramadol on the Neuropathic Pain in Rats

Song, Kyung Wha; Kim, Hyun Jeong; Yum, Kwang Won

Abstract

BACKGROUND: Tramadol is known to be a weak opioid. However, it has also been shown that tramadol is an effective norepinephrine and serotonin uptake blocker, which may be effective in the treatment of neuropathic pain. The present study was undertaken in order to assess the antinociceptive action of tramadol and to investigate possible antinociceptive mechanisms by using antagonists in an animal neuropathic pain models in rats.
METHODS
Rats were prepared with tight ligation at the left 5 and 6th lumbar spinal nerves (Kim and Chung's neuropathic pain model). The antinociceptive effects of tramadol (10, 20, and 50 mg/kg i.p.) in rats with neuropathic pain were assessed. Additionally, following coadministration of antagonists such as naloxone (1 mg/kg i.p.), yohimbine (1 mg/kg i.p.) and ritanserin (1 mg/kg i.p.) with 50 mg/kg of tramadol, the responses to mechanical and thermal stimuli were measured over a two-hour period.
RESULTS
Tramadol displayed potent antinociceptive effects in a dose-dependent manner on rats with neuropathic pain (P<0.05). The effects of tramadol were inhibited by coadministered naloxone and yohimbine in rats with mechanical and thermal allodynia, respectively (P<0.05). However, there were no significant changes in the pain behaviors in the case of ritanserin.
CONCLUSIONS
Tramadol showed significant antinociceptive effects in rats with regards to neuropathic pain against both mechanical and thermal allodynia. The antinociceptive effect on the mechanical stimuli is medicated via an opioid receptor. However, it appears that the antinociceptive effects on thermal allodynia are mediated via a noradrenalin receptor vice a serotonergic receptor.