Title:Non-canonical Molecular Targets for Novel Analgesics: Intracellular Calcium and HCN Channels
Volume: 19
Issue: 11
Author(s): Daniel C. Cook and Peter A. Goldstein*
Affiliation:
- Department of Anesthesiology, Weill Cornell Medicine, New York, NY 10065,United States
Keywords:
Neuropathic pain, drug development, HCN, ryanodine receptor, analgesic, antihyperalgesic.
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.
