压力在肿瘤学患者的症状负担中起着重要作用，并可能加重许多类化疗药物的主要不良反应之一，即癌症化疗诱导的外周神经病变（CIPN）。我们探讨了压力在奥沙利铂诱导的疼痛持续期中的作用。在雄性大鼠中，奥沙利铂诱导了过敏性启动，这是一种转变为慢性疼痛的模型，表现为前列腺素E 2 引起的过敏性持续延长，而在剜去肾上腺的大鼠中明显减弱。在新生儿处理方案下，成年大鼠中引起压力耐受性，可以预防奥沙利铂引起的过敏性启动。为了阐明下丘脑-垂体-肾上腺和交感-肾上腺神经内分泌应激轴在奥沙利铂CIPN中的作用，我们使用针对介导儿茶酚胺和糖皮质激素效应的受体mRNA及其第二信使的反义寡核苷酸（ODN）进行脊髓内给药，以减少其在伤害感受器中的表达。虽然脊髓内给药β 2 -肾上腺素能和糖皮质激素受体反义ODN可以减轻奥沙利铂引起的过敏性启动，但β 2 -肾上腺素能受体反义只能减轻奥沙利铂引起的过敏性疼痛。百日咳毒素的给药减轻了过敏性启动，这是一种非选择性抑制Gα i/o蛋白的抑制剂。抗Gα i1 和 Gα o的ODN也减轻了过敏性启动。此外，蛋白激酶Cε的反义寡核苷酸，这是一种参与I型过敏性启动的第二信使，也减轻了奥沙利铂引起的过敏性启动。I型（cordycepin）和II型（SSU6656和U0126）过敏性启动维持的第二信使的抑制剂均减轻了过敏性启动。这些实验支持了神经内分泌应激轴在奥沙利铂CIPN中的过敏性启动的作用，对于雄性大鼠具有重要意义。版权所有 ©2023作者。由Wolters Kluwer Health，Inc.代表国际疼痛研究协会出版。

Stress plays a major role in the symptom burden of oncology patients and can exacerbate cancer chemotherapy-induced peripheral neuropathy (CIPN), a major adverse effect of many classes of chemotherapy. We explored the role of stress in the persistent phase of the pain induced by oxaliplatin. Oxaliplatin induced hyperalgesic priming, a model of the transition to chronic pain, as indicated by prolongation of hyperalgesia produced by prostaglandin E 2 , in male rats, which was markedly attenuated in adrenalectomized rats. A neonatal handling protocol that induces stress resilience in adult rats prevented oxaliplatin-induced hyperalgesic priming. To elucidate the role of the hypothalamic-pituitary-adrenal and sympathoadrenal neuroendocrine stress axes in oxaliplatin CIPN, we used intrathecally administered antisense oligodeoxynucleotides (ODNs) directed against mRNA for receptors mediating the effects of catecholamines and glucocorticoids, and their second messengers, to reduce their expression in nociceptors. Although oxaliplatin-induced hyperalgesic priming was attenuated by intrathecal administration of β 2 -adrenergic and glucocorticoid receptor antisense ODNs, oxaliplatin-induced hyperalgesia was only attenuated by β 2 -adrenergic receptor antisense. Administration of pertussis toxin, a nonselective inhibitor of Gα i/o proteins, attenuated hyperalgesic priming. Antisense ODNs for Gα i 1 and Gα o also attenuated hyperalgesic priming. Furthermore, antisense for protein kinase C epsilon, a second messenger involved in type I hyperalgesic priming, also attenuated oxaliplatin-induced hyperalgesic priming. Inhibitors of second messengers involved in the maintenance of type I (cordycepin) and type II (SSU6656 and U0126) hyperalgesic priming both attenuated hyperalgesic priming. These experiments support a role for neuroendocrine stress axes in hyperalgesic priming, in male rats with oxaliplatin CIPN.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.