Gabapentin and NMDA receptor antagonists interacts synergistically to alleviate allodynia in two rat models of neuropathic pain
| Autor: | Tiansheng Shi, Zsuzsanna Wiesenfeld-Hallin, Jing-Xia Hao, Xiao-Jun Xu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Side effect Gabapentin Pharmacology Dextromethorphan Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine medicine Animals Spinal Cord Injuries Behavior Animal Dose-Response Relationship Drug business.industry Nerve injury Sciatic nerve injury medicine.disease Sciatic Nerve Rats 030104 developmental biology Anesthesiology and Pain Medicine Allodynia Hyperalgesia Touch Neuropathic pain Neuralgia NMDA receptor Female Neurology (clinical) Dizocilpine Maleate medicine.symptom business Excitatory Amino Acid Antagonists 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Scandinavian Journal of Pain. 18:687-693 |
| ISSN: | 1877-8879 1877-8860 |
| DOI: | 10.1515/sjpain-2018-0083 |
| Popis: | 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. Methods 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. Results 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. Conclusions 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. Implications Combining NMDA receptor antagonists with gabapentin may provide a new approach in alleviating neuropathic pain with increased efficacy and reduced side effects. |
| Databáze: | OpenAIRE |
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