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Review
. 2021;19(11):1937-1951.
doi: 10.2174/1570159X19666210119153047.

Non-canonical Molecular Targets for Novel Analgesics: Intracellular Calcium and HCN Channels

Daniel C Cook  1 , Peter A Goldstein  1
Affiliations
Review

Non-canonical Molecular Targets for Novel Analgesics: Intracellular Calcium and HCN Channels

Daniel C Cook et al. Curr Neuropharmacol. 2021.

Abstract

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.

Keywords: HCN; Neuropathic pain; analgesic; antihyperalgesic.; drug development; ryanodine receptor.

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