Analgesic synergism of gabapentin and carbamazepine in rat model of diabetic neuropathic pain

Sinan Mohammed Abdullah Al-Mahmood,Tariq Abdul Razak,Nik Nur Fatnoon Nik Ahmad,Shahrin Tarmizi Bin Che Abdullah,Abdul Hadi Bin Mohamed

doi:10.4314/tjpr.v15i6.11

Sinan Mohammed Abdullah Al-Mahmood, Tariq Abdul Razak + Show 3 more

Open Access

https://doi.org/10.4314/tjpr.v15i6.11

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Abstract

Purpose: To evaluate synergy in the analgesic effects of a combination therapy of carbamazepine (CBZ) and gabapentin (GBP) in diabetic neuropathic pain.Methods: Neuropathic pain was produced in rats by a single intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg. CBZ, GBP, and their combination were orally administered at varying doses (GBP 30 - 180 mg/kg; CBZ 20 - 40 mg/kg) comparable to their therapeutic doses in humans. Nociceptive responses in the diabetic rats were assessed using hot plate test.Results: Hot plate latency significantly increased with oral administration of GBP at a dose of 180 mg/kg when compared with control group (p < 0.05), while at a dose of 90 mg/kg, the increase was not significant. Oral administration of CBZ at doses of 20 and 40 mg/kg did not produce any significant impact on hot plate latency. However, a combination of GBP at 90 mg/kg and CBZ at 20 mg/kg produced significant increase in latency, compared with control group and other groups (p < 0.05), except the group that received 180 mg/kg GBP. The combination of low dose GBP 30 mg/kg and carbamazepine 30 mg/kg had no significant effect on latency (p > 0.05).Conclusion: The results obtained in this study provide useful information on the combination therapy of GBP and CBZ, which may be applied in the treatment of pain in diabetic neuropathy.Keywords: Diabetic neuropathy, Carbamazepine, Gabapentin, Hot-plate test

Highlights

Diabetic neuropathy is a common and costly complication of both types of diabetes (I and II)
Earlier studies recommended that CBZ might be effective in diabetic neuropathy and, in France; CBZ is endorsed for treating neuropathic pain in adults
Hot plate latencies significantly increased with oral administration of GBP at a dose of 180 mg/kg when compared with control group (p < 0.05), while at a dose of 90 mg/kg, the increase was not statistically significant

Summary

Introduction

Diabetic neuropathy is a common and costly complication of both types of diabetes (I and II). Increasing evidence suggest that pre-diabetic conditions are associated with some forms of neuropathy [2]. A variety of anticonvulsants and local anaesthetic drugs suppress abnormal discharge originating at nerve injury sites and associated dorsal root ganglions (DRGs) via sodium channel blockage. These include CBZ, phenytoin, tocainide, and lidocaine [4]. CBZ is the first antiepileptic drug utilized in many clinical trials and has been used for long to manage diabetic neuropathy pain [5]. Earlier studies recommended that CBZ might be effective in diabetic neuropathy and, in France; CBZ is endorsed for treating neuropathic pain in adults. CBZ appears to limit the repetitive firing of action potentials evoked by a sustained depolarization by slowing down the rate of recovery of voltage-activated Na+ channels [7]

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Discussion

Conclusion