Department of Anesthesiology, Weill Cornell Medicine, New York, NY 10065, United States.
Curr Neuropharmacol. 2021;19(11):1937-1951. doi: 10.2174/1570159X19666210119153047.
Pain is a prevalent biopsychosocial condition that poses a significant challenge to healthcare providers, contributes substantially to a disability, and is a major economic burden worldwide. An overreliance on opioid analgesics, which primarily target the μ-opioid receptor, has caused devastating morbidity and mortality in the form of misuse and overdose-related death. Thus, novel analgesic medications are needed that can effectively treat pain and provide an alternative to opioids. A variety of cellular ion channels contribute to nociception, the response of the sensory nervous system to a noxious stimulus that commonly leads to pain. Ion channels involved in nociception may provide a suitable target for pharmacologic modulation to achieve pain relief. This narrative review summarizes the evidence for two ion channels that merit consideration as targets for non-opioid pain medications: ryanodine receptors (RyRs), which are intracellular calcium channels, and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which belong to the superfamily of voltage-gated K+ channels. The role of these channels in nociception and neuropathic pain is discussed and suitability as targets for novel analgesics and antihyperalgesics is considered.
疼痛是一种普遍存在的生物心理社会状况，给医疗保健提供者带来了重大挑战，极大地导致了残疾，并在全球范围内造成了重大的经济负担。过度依赖主要针对μ-阿片受体的阿片类镇痛药，已经导致了滥用和过量相关死亡的灾难性发病率和死亡率。因此，需要新型的镇痛药，能够有效地治疗疼痛，并提供阿片类药物的替代物。各种细胞离子通道参与伤害感受，即感觉神经系统对有害刺激的反应，通常会导致疼痛。参与伤害感受的离子通道可能为药物调节提供合适的靶点，以实现止痛。本综述总结了两种离子通道作为非阿片类止痛药靶点的证据：肌质网钙通道（RyR）和超极化激活环核苷酸门控（HCN）通道，它们属于电压门控 K+通道的超家族。讨论了这些通道在伤害感受和神经性疼痛中的作用，并考虑了它们作为新型镇痛药和抗痛觉过敏剂靶点的适用性。
