Role of serotonin 5-HT1A and opioid receptors in the antiallodynic effect of tramadol in the chronic constriction injury model of neuropathic pain in rats
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Tramadol (1RS, 2RS)-2-[(dimethylamino)-methyl]-1-(3-methoxyphenyl)-cyclohexanol) is an atypical centrally acting analgesic agent with weak opioid receptor affinity that, like some antidepressants, enhances the extraneuronal concentrations of the monoamine neurotransmitters, noradrenaline and serotonin, by interfering with their re-uptake and release mechanisms.
The present study was undertaken to evaluate the potential role of 5-HT1A receptors and opioids receptors in the analgesic effect of tramadol in neuropathic pain. With this aim, the effect of either a selective 5-HT1A receptor antagonist (WAY-100635, N-2-[4-(2-methoxyphenyl-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexane carboxamide) or a selective 5-HT1A receptor agonist (8-OH-DPAT, 8-hydroxy-2-(di-n-propylamine) tetralin hydrobromide) or an opioid receptor antagonist (naloxone; naloxone hydrochloride dihydrate) was investigated in combination with tramadol by means of the cold-plate test in the chronic constriction injury model in rats.
The results showed that WAY-100635 (0.8 mg/kg) significantly enhanced the antiallodynic effect of non-effective doses of tramadol (5–10 mg/kg). In contrast, 8-OH-DPAT (0.5 mg/kg) counteracted the antiallodynic effect of an effective dose of tramadol (22 mg/kg). Naloxone (0.5 mg/kg) partially counteracted the antiallodynic effect of tramadol (22 mg/kg).
These findings suggest the involvement of opioid and 5-HT1A receptors in the antinociceptive effect of tramadol and support the idea that the combination of tramadol with compounds having 5-HT1A antagonist properties could be a new strategy to improve tramadol-induced analgesia in neuropathic pain.
KeywordsSerotonin Serotonin 5-HT1A receptors Neuropathic pain Tramadol Opioid receptors Rat
This study has been supported by “Fondo de Investigación Sanitaria” (PI031430) from Instituto de Salud Carlos III and “Plan Andaluz de Investigación” (CTS-510) from Junta de Andalucía. The authors thank to Dr. Thomas Christoph for their help and cooperation in the revision of the manuscript.
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