Ungard Robert G, Zhu Yong Fang, Yang Sarah, Nakhla Peter, Parzei Natalka, Zhu Kan Lun, Singh Gurmit
Michael G. DeGroote Institute for Pain Research and Care, Medicine, McMaster University, Hamilton, Ontario, Canada.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Can J Pain. 2020 Feb 28;4(1):39-58. doi: 10.1080/24740527.2020.1724776.
: Cancer pain involves nervous system damage and pathological neurogenesis. Neuropathic pain arises from damage to the nervous system and is driven by ectopic signaling. Both progesterone and pregabalin are neuroprotective in animal models, and there is evidence that both drugs bind to and inhibit voltage-gated calcium channels. : This study was designed to characterize the effects of progesterone and pregabalin in preclinical models of cancer and neuropathic pain in both sexes. : We measured peripheral sensory signaling by intracellular in vivo electrophysiology and behavioral indicators of pain in rat models of cancer-induced bone pain and neuropathic pain. : Female but not male models of cancer pain showed a behavioral response to treatment and pregabalin reduced excitability in C and A high-threshold but not low-threshold sensory neurons of both sexes. Male models of neuropathic pain treated with pregabalin demonstrated higher signaling thresholds only in A high-threshold neurons, and behavioral data indicated a clear recovery to baseline mechanical withdrawal thresholds in all treatment groups. Female rat treatment groups did not show excitability changes in sensory neurons, but all demonstrated higher mechanical withdrawal thresholds than vehicle-treated females, although not to baseline levels. Athymic female rat models of neuropathic pain showed no behavioral or electrophysiological responses to treatment. : Both pregabalin and progesterone showed evidence of efficacy in male models of neuropathic pain. These results add to the evidence demonstrating differential effects of treatments for pain in male and female animals and widely differing responses in models of cancer and neuropathic pain.
癌症疼痛涉及神经系统损伤和病理性神经发生。神经性疼痛源于神经系统损伤，并由异位信号驱动。孕酮和普瑞巴林在动物模型中均具有神经保护作用，且有证据表明这两种药物均能结合并抑制电压门控钙通道。本研究旨在表征孕酮和普瑞巴林在两性癌症和神经性疼痛临床前模型中的作用。我们通过细胞内体内电生理学测量外周感觉信号，并在癌症诱导的骨痛和神经性疼痛大鼠模型中测量疼痛的行为指标。癌症疼痛的雌性而非雄性模型对治疗有行为反应，普瑞巴林降低了两性C类和A类高阈值而非低阈值感觉神经元的兴奋性。用普瑞巴林治疗的神经性疼痛雄性模型仅在A类高阈值神经元中表现出更高的信号阈值，行为数据表明所有治疗组的机械性撤腿阈值均明显恢复至基线水平。雌性大鼠治疗组在感觉神经元中未表现出兴奋性变化，但所有组均表现出比用赋形剂处理的雌性大鼠更高的机械性撤腿阈值，尽管未恢复至基线水平。神经性疼痛的无胸腺雌性大鼠模型对治疗未表现出行为或电生理反应。普瑞巴林和孕酮在神经性疼痛雄性模型中均显示出疗效证据。这些结果进一步证明了在雄性和雌性动物中疼痛治疗效果存在差异，以及在癌症和神经性疼痛模型中反应差异很大。
