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Venlafaxine compromises the antinociceptive actions of gabapentin in rat models of neuropathic and persistent pain

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Abstract

Rationale

Neuropathic pain is associated with a number of disease states of diverse aetiology that can share common pathophysiological mechanisms. Antiepileptic drugs modulate ion channel function and antidepressants increase extracellular monoamine levels, and both drug classes variously attenuate signs and symptoms of neuropathic pain. Thus, coadministration of the antiepileptic gabapentin and the antidepressant venlafaxine may provide superior pain relief to administration of either drug alone.

Objectives

To systematically establish the pain relieving efficacies of venlafaxine and gabapentin alone and in combination.

Materials and methods

Gabapentin (50 and 100 mg/kg, s.c.) and venlafaxine (10, 25, 50 mg/kg, s.c.) were tested alone or in combination in the rat spared nerve injury (SNI) model of neuropathic pain and the rat formalin test of persistent pain. Diuresis was measured in a separate experiment after administration of venlafaxine.

Results

Hindpaw mechanical allodynia was dose-dependently reversed by gabapentin (50 and 100 mg/kg, s.c.), whereas venlafaxine was ineffective (10 and 50 mg/kg, s.c.). Both gabapentin and venlafaxine also attenuated hindpaw mechanical hyperalgesia. Surprisingly, coadministration of venlafaxine (50 mg/kg) significantly lowered the antiallodynic effect of both doses of gabapentin by up to 60% in spared-nerve-injury rats and a negative antinociceptive interaction between gabapentin and venlafaxine was also observed in the rat formalin test. We demonstrated that venlafaxine administration was associated with a dose-dependent increase in urine output over the time course of the nociceptive experiments.

Conclusion

Venlafaxine compromises the antiallodynic effects of coadministered gabapentin most probably as consequence-increased diuresis.

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Acknowledgements

We would like to thank Wyeth (USA) and Pliva Pharma (Denmark) for providing us with venlafaxine and gabapentin for use in this study, respectively. We would also like to thank Dorthe Gybel Jensen for expert technical assistance. FR was supported by a fellowship from the Danish University of Pharmaceutical Sciences and financial support was also provided by The J. Juhland and Wife Memorial Foundation.

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Authors and Affiliations

  1. Department of Pharmacology, Danish University of Pharmaceutical Sciences, Jagtvej 120, Copenhagen, Denmark

    Frederik Rode, Tine Broløs & Ole J. Bjerrum

  2. Department of Pharmacology, Neurosearch A/S, Pederstrupvej 93, Ballerup, 2750, Denmark

    Gordon Blackburn-Munro

  3. Astellas CNS Research in Edinburgh, Division of Neuroscience, University of Edinburgh, The Chancellor’s Building, 49 Little France Crescent, EH16 4SB, Edinburgh, Scotland

    Frederik Rode

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  1. Frederik Rode
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  2. Tine Broløs
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Correspondence to Frederik Rode.

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Rode, F., Broløs, T., Blackburn-Munro, G. et al. Venlafaxine compromises the antinociceptive actions of gabapentin in rat models of neuropathic and persistent pain. Psychopharmacology 187, 364–375 (2006). https://doi.org/10.1007/s00213-006-0430-3

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  • DOI: https://doi.org/10.1007/s00213-006-0430-3

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