Neuronal transient receptor potential (TRP) channels and noxious sensory detection in sickle cell disease

Neurosci Lett. 2019 Feb 16;694:184-191. doi: 10.1016/j.neulet.2018.11.056. Epub 2018 Nov 30.


Pain is the leading cause for hospitalization in patients with sickle cell disease (SCD). While the characteristics of SCD pain can vary widely between patients and between phases of the disease (e.g. vasoocclusive crisis pain vs. chronic pain), similar neuronal mechanisms likely underlie the various aspects of nociceptive processing. In the peripheral nervous system, small unmyelinated C fibers and lightly-myelinated Aδ fibers detect and transmit noxious stimuli. Both classes of neurons express members of the transient receptor potential (TRP) family, a group of ligand gated ion-channels that are activated by thermal, chemical, and mechanical stimuli. Promiscuous TRP channel family members are activated by a wide range of stimuli, many of which are dysregulated in patients with SCD and transgenic SCD mouse models. In 2011, our lab published the first report of TRP channel contributions to rodent SCD pain. Since that time, additional basic and clinical research efforts have investigated the genetic and biochemical status of TRP channels in SCD, placing particular focus on TRPV1. This review will discuss these advances and highlight the clinical SCD presentations that have not yet been studied, but which may be mediated by TRP channel activity.

Keywords: Pain; Sickle cell disease; TRPA1; TRPM8; TRPV1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / physiopathology*
  • Animals
  • Humans
  • Hyperalgesia / complications
  • Nociception / physiology*
  • Pain / complications
  • Pain / physiopathology*
  • TRPA1 Cation Channel / physiology
  • TRPM Cation Channels / physiology
  • TRPV Cation Channels / physiology
  • Transient Receptor Potential Channels / physiology*


  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • TRPM Cation Channels
  • TRPM8 protein, human
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Transient Receptor Potential Channels