Open AccessNon-canonical Molecular Targets for Novel Analgesics: Intracellular Calcium and HCN Channels
Author(s) -
Daniel C. Cook,
Peter A. Goldstein
Publication year - 2021
Publication title -
current neuropharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.955
H-Index - 73
eISSN - 1875-6190
pISSN - 1570-159X
DOI - 10.2174/1570159x19666210119153047
Subject(s) - neuropathic pain , medicine , nociception , neuroscience , opioid , analgesic , transient receptor potential channel , ion channel , noxious stimulus , voltage dependent calcium channel , chronic pain , pharmacology , bioinformatics , receptor , calcium , biology , psychiatry
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.