Targeting the Sphingosine-1-Phosphate Axis for Developing Non-narcotic Pain Therapeutics

Trends Pharmacol Sci. 2020 Nov;41(11):851-867. doi: 10.1016/j.tips.2020.09.006. Epub 2020 Oct 1.

Abstract

Chronic pain is a life-altering condition affecting millions of people. Current treatments are inadequate and prolonged therapies come with severe side effects, especially dependence and addiction to opiates. Identification of non-narcotic analgesics is of paramount importance. Preclinical and clinical studies suggest that sphingolipid metabolism alterations contribute to neuropathic pain development. Functional sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) antagonists, such as FTY720/fingolimod, used clinically for non-pain conditions, are emerging as non-narcotic analgesics, supporting the repurposing of fingolimod for chronic pain treatment and energizing drug discovery focused on S1P signaling. Here, we summarize the role of S1P in pain to highlight the potential of targeting the S1P axis towards development of non-narcotic therapeutics, which, in turn, will hopefully help lessen misuse of opioid pain medications and address the ongoing opioid epidemic.

Keywords: S1P receptors; neuroinflammation; neuropathic pain; non-narcotic treatments; sphingosine-1-phosphate (S1P).

Publication types

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

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology*
  • Animals
  • Chronic Pain / drug therapy*
  • Chronic Pain / metabolism
  • Humans
  • Lysophospholipids / metabolism*
  • Molecular Targeted Therapy
  • Pain Management / methods*
  • Signal Transduction / drug effects
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism
  • Sphingosine-1-Phosphate Receptors / antagonists & inhibitors*
  • Sphingosine-1-Phosphate Receptors / metabolism

Substances

  • Analgesics, Non-Narcotic
  • Lysophospholipids
  • Sphingosine-1-Phosphate Receptors
  • sphingosine 1-phosphate
  • Sphingosine