• Hong Xie, Zhi-Qiang Dong, Fei Ma, William R Bauer, Xin Wang, and Gen-Cheng Wu.
• Department of Integrative Medicine, Institute of Acupuncture Research, Shanghai Medical College of Fudan University, Shanghai 200032, China.
• Brain Res. 2008 May 19;1210:76-83.

AbstractThe analgesic effects of tramadol are considered to be mediated by both the opioid system and the serotonergic system. This study investigated the involvement of a subtype of serotonin receptors, 5-hydroxytryptamine (5-HT)2A receptor, in the analgesic effect of tramadol. The intraperitoneal (i.p.) injection of tramadol reduced the paw withdrawal latency (PWL) to radiant heat testing in mono-arthritic rats. The antagonistic effect of i.p. ketanserin (a 5-HT2A receptor antagonist) on tramadol analgesia was observed. The expression of the 5-HT2A receptor mRNA in the nucleus of raphe magnus (NRM), ventrolateral periaqueductal gray (vlPAG) and spinal dorsal horn of mono-arthritic rats after a ten-day treatment with tramadol was measured with in situ hybridization. Either single injections or 10 days of tramadol treatment dose-dependently elevated PWL of arthritic rats while ketanserin could partially antagonize the tramadol analgesic effect. Expression of the 5-HT2A receptor mRNA in NRM, ipsilateral vlPAG, and the ipsilateral spinal dorsal horn of arthritic rats was significantly increased after tramadol treatment. These results suggest that 5-HT2A receptors are involved in the analgesic effect of tramadol. This study provides evidence for involvement of 5-HT2A receptors in the tramadol analgesia of inflammatory pain. The increase in this receptor mRNA in the chronic study may contribute to the sustaining effect of tramadol long-term treatments in clinical practice.

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