, Volume 193, Issue 1, pp 97–105

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

  • Esther Berrocoso
  • M. Dolores De Benito
  • Juan A. Mico
Original Investigation

DOI: 10.1007/s00213-007-0761-8

Cite this article as:
Berrocoso, E., De Benito, M.D. & Mico, J.A. Psychopharmacology (2007) 193: 97. doi:10.1007/s00213-007-0761-8



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.


Serotonin Serotonin 5-HT1A receptors Neuropathic pain Tramadol Opioid receptors Rat 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Esther Berrocoso
    • 1
  • M. Dolores De Benito
    • 1
  • Juan A. Mico
    • 1
  1. 1.Pharmacology and Neuroscience Research Group, Department of Neuroscience (Pharmacology and Psychiatry), School of MedicineUniversity of CádizCadizSpain

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