Elsevier

Neurobiology of Pain

Volume 7, January–July 2020, 100044
Neurobiology of Pain

Review
Molecular mechanisms of cold pain

https://doi.org/10.1016/j.ynpai.2020.100044Get rights and content
Under a Creative Commons license
open access

Highlights

  • The sensation of cooling is essential for survival.

  • Ion channels expressed in peripheral cold-sensing neurons transduce cold stimuli.

  • Sodium and potassium channels control terminal excitability at low temperatures.

  • Chronic pain patients with cold allodynia experience mild cooling as pain.

  • Changes in sensory neuron excitability drive cold allodynia.

Abstract

The sensation of cooling is essential for survival. Extreme cold is a noxious stimulus that drives protective behaviour and that we thus perceive as pain. However, chronic pain patients suffering from cold allodynia paradoxically experience innocuous cooling as excruciating pain. Peripheral sensory neurons that detect decreasing temperature express numerous cold-sensitive and voltage-gated ion channels that govern their response to cooling in health and disease. In this review, we discuss how these ion channels control the sense of cooling and cold pain under physiological conditions, before focusing on the molecular mechanisms by which ion channels can trigger pathological cold pain. With the ever-rising number of patients burdened by chronic pain, we end by highlighting the pressing need to define the cells and molecules involved in cold allodynia and so identify new, rational drug targets for the analgesic treatment of cold pain.

Keywords

Pain
Ion channels
Thermosensation
Nociception
Cold
Cold allodynia
Neuropathic pain
Dorsal root ganglion

Cited by (0)

1

ORCID: 0000-0002-4863-1093.