Although N-type voltage-gated calcium channels (VGCCs) are implicated in neuropathic pain, their biological ramifications are unknown. As a result, we investigated the neuroprotective efficacy of topiramate (TPM) and zonisamide (ZNS) against peripheral neuropathy in the CaV2.2-alpha2/delta1-beta1 subtype of VGCC. The molecular docking analysis was conducted using a protein database to uncover the role of the human N-type VGCCs CaV2.2-alpha2/delta1-beta1 (7 VFV). Male Albino Wistar rats were treated for sciatic nerve constriction injury and a single intraperitoneal injection of streptozotocin (60 mg/kg). Following the 2-week post-neuropathy, 20 mg/ kg/day intraperitoneal injections of TPM and ZNS were given. At the conclusion of each week, behavioural signs, such as allodynia and hyperalgesia, were evaluated. Following that, the sciatic nerve was extracted, the homogenate was used for biochemical analysis, and a histological study was performed. TPM and ZNS were discovered to be effective CaV2.2-alpha2/delta1-beta1 blockers via molecular docking. Total calcium and Ca2+ ATPase levels in the tissues were also found to be lower. TPM and ZNS significantly reduced allodynia and hyperalgesia while also exhibiting helpful antioxidant qualities by lowering malonaldehyde and nitric oxide and raising glutathione, superoxide dismutase, and catalase levels. Furthermore, pro-inflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, were reduced. Histopathological investigation revealed normal morphology of the sciatic nerve with no evidence of neuropathy. TPM and ZNS inhibit the CaV2.2-alpha2/delta1-beta1 in sciatic nerves and alleviate a state of neuropathy.
Key words: N-type voltage-gated calcium channel (VGCC), allodynia and hyperalgesia, antioxidants, cytokines, molecular docking.
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