BACKGROUND Chemotherapy induced peripheral neuropathy (CIPN) has been attributed to chemotherapeutic agents such as cisplatin which adversely affect disease outcome leading to increased cancer related morbidity. The clinical efficacy of systemic gabapentin in neuropathic pain management is limited by central side-effects in addition to a scarceness of conclusive evidence of its efficacy in CIPN management. The topical route therefore may provide a relatively safe alternative for neuropathic pain treatment in general and CIPN in particular. METHODS Cisplatin induced neuropathic nociception was established in rats after a single weekly cisplatin injection (3.0 mg/kg, intraperitoneally) for 4 weeks. The evoked neuropathic sensation of allodynia was assessed by plantar application of von Frey monofilaments as the paw withdrawal threshold (PWT), whereas the expression of heat-hypoalgesia was determined on a hot-plate as paw withdrawal latency (PWL). Gabapentin gel (10% w/w) was applied three-times daily on the hind paws while in a concurrent systemic study, gabapentin was administered daily (75 mg/kg, intraperitoneally) for 4 weeks. To assess any evidence of neurological adverse symptoms of cisplatin and the central side-effect propensity of systemic or topical gabapentin, evaluation of motor coordination (rotarod test) and gait (footprint analysis) were performed. RESULTS Cisplatin invoked a progressive development of neuropathic hind paw allodynia (decreased PWT, days 7-28) and heat hypoalgesia (increased PWL, days 21-28). Topical gabapentin significantly delayed the expression of both allodynia on protocol days 21 and 28 and heat-hypoalgesia (day 28). Systemic gabapentin displayed a comparative anti-neuropathic predisposition through a sustained suppression of tactile allodynia on days 14 and 21-28 as well as thermal hypoalgesia (days 21 and 28). Systemic gabapentin also impaired motor coordination and gait thus affirming its clinically documented central side effects, but these outcomes were not evident after topical treatment. CONCLUSIONS Both topical and systemic gabapentin exhibit a propensity to attenuate CIPN in a cisplatin paradigm. Gabapentin applied topically may therefore provide an adjunctive or alternative route for CIPN management upon cessation of systemic medications due to intolerable side-effects.

中文翻译：

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局部加巴喷丁凝胶在化疗引起的周围神经病变的顺铂范例中的疗效。


背景化疗引起的周围神经病(CIPN)归因于诸如顺铂之类的化疗剂，其对疾病结果产生不利影响，导致癌症相关发病率增加。全身性加巴喷丁在神经病理性疼痛治疗中的临床疗效受到中枢副作用的限制，此外还缺乏其在 CIPN 治疗中疗效的确凿证据。因此，局部途径可能为一般的神经性疼痛治疗，特别是 CIPN 提供相对安全的替代方案。方法 每周单次注射顺铂（3.0 mg/kg，腹膜内注射）4周后，在大鼠中建立顺铂诱导的神经性伤害感受。通过在足底应用冯弗雷单丝作为缩爪阈值（PWT）来评估诱发的异常性疼痛的神经性感觉，而热痛觉减退的表达在热板上作为缩爪潜伏期（PWL）来确定。加巴喷丁凝胶（10% w/w）每天三次涂抹在后爪上，而在一项同时进行的全身研究中，每天给予加巴喷丁（75 mg/kg，腹膜内注射），持续 4 周。为了评估顺铂的神经系统不良症状和全身或局部加巴喷丁的中枢副作用倾向的任何证据，进行了运动协调性（旋转测试）和步态（足迹分析）的评估。结果 顺铂引起神经性后爪异常性疼痛（PWT 减少，第 7-28 天）和热痛觉减退（PWL 增加，第 21-28 天）的逐渐发展。局部加巴喷丁显着延迟了方案第 21 天和第 28 天的异常性疼痛以及热痛觉减退（第 28 天）的表达。 全身加巴喷丁通过持续抑制第14天和第21-28天的触觉异常性疼痛以及热痛觉减退（第21天和第28天）表现出相对的抗神经病倾向。全身加巴喷丁还会损害运动协调和步态，从而证实其临床记录的中枢副作用，但这些结果在局部治疗后并不明显。结论 在顺铂范式中，局部加巴喷丁和全身加巴喷丁均表现出减弱 CIPN 的倾向。因此，在由于无法耐受的副作用而停止全身药物治疗后，局部应用加巴喷丁可能为 CIPN 管理提供辅助或替代途径。