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Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald

4 Issues per year

CiteScore 2017: 0.84

SCImago Journal Rank (SJR) 2017: 0.401
Source Normalized Impact per Paper (SNIP) 2017: 0.452

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Volume 18, Issue 4

Gabapentin and NMDA receptor antagonists interacts synergistically to alleviate allodynia in two rat models of neuropathic pain

Tiansheng Shi
  • Corresponding author
  • Department of Physiology and Pharmacology, Section of Integrative Pain Research, Karolinska Institutet, S-171 77 Stockholm, Sweden
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jing-Xia Hao
  • Department of Physiology and Pharmacology, Section of Integrative Pain Research, Karolinska Institutet, Stockholm, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Zsuzsanna Wiesenfeld-Hallin
  • Department of Physiology and Pharmacology, Section of Integrative Pain Research, Karolinska Institutet, Stockholm, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Xiao-Jun Xu
  • Department of Physiology and Pharmacology, Section of Integrative Pain Research, Karolinska Institutet, Stockholm, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-07-05 | DOI: https://doi.org/10.1515/sjpain-2018-0083


Background and aims

The clinical management of neuropathic pain remains a challenge. We examined the interaction between gabapentin and NMDA receptor antagonists dextromethrophan and MK-801 in alleviating neuropathic pain-like behaviors in rats after spinal cord or sciatic nerve injury.


Female and male rats were produced with Ischemic spinal cord injury and sciatic nerve injury. Gabapentin, dextromethorphan, MK-801 or drug combinations were injected with increasing doses. Mechanical response thresholds were tested with von Frey hairs to graded mechanical touch/pressure, and ethyl chloride spray was applied to assess the cold sensitivity before and after injuries.


In spinally injured rats, gabapentin and dextromethorphan did not affect allodynia-like behaviors at doses of 30 and 20 mg/kg, respectively. In contrast, combination of 15 or 30 mg/kg gabapentin with dextromethorphan at 10 mg/kg produced total alleviation of allodynia to mechanical or cold stimulation. Further reducing the dose of gapapentin to 7.5 mg/kg and dextromethorphan to 5 mg/kg still produced significant effect. MK-801, another NMDA receptor antagonist, also enhanced the effect of gabapentin in spinally injured rats. Similar synergistic anti-allodynic effect between dextromethorphan and gabapentin was also observed in a rat model of partial sciatic nerve injury. No increased side effect was seen following the combination between gabapentin and dextromethorphan.


In conclusion, the present study suggested that combining NMDA receptor antagonists with gabapentin could provide synergistic effect to alleviate neuropathic pain and reduced side effects.


Combining NMDA receptor antagonists with gabapentin may provide a new approach in alleviating neuropathic pain with increased efficacy and reduced side effects.

Keywords: anti-convulsant; dextromethorphan; MK-801; nerve injury; spinal cord injury


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About the article

Received: 2018-05-09

Revised: 2018-06-11

Accepted: 2018-06-12

Published Online: 2018-07-05

Published in Print: 2018-10-25

Authors’ statements

Research Funding: This study was supported by the Swedish Science Council (Proj. 12168) and research funds of the Karolinska Institutet and China Scholarship Council.

Conflict of interest: We declare no conflicts of interests.

Informed consent: Not applicable.

Ethical approval: All experiments were approved by the local research ethics committee and were conducted in accordance with research guidelines of the International Association for the Study of Pain. We have used the minimal number of animals that is required to obtain results for statistical analysis.

Citation Information: Scandinavian Journal of Pain, Volume 18, Issue 4, Pages 687–693, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1515/sjpain-2018-0083.

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©2018 Scandinavian Association for the Study of Pain. Published by Walter de Gruyter GmbH, Berlin/Boston. All rights reserved..Get Permission

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