Sigma 1 receptor: a new therapeutic target for pain

Eur J Pharmacol. 2013 Sep 15;716(1-3):78-93. doi: 10.1016/j.ejphar.2013.01.068. Epub 2013 Mar 13.


Sigma 1 receptor (σ₁ receptor) is a unique ligand-regulated molecular chaperone located mainly in the endoplasmic reticulum and the plasma membrane. σ₁ receptor is activated under stress or pathological conditions and interacts with several neurotransmitter receptors and ion channels to modulate their function. The effects reported preclinically with σ₁ receptor ligands are consistent with a role for σ₁ receptor in central sensitization and pain hypersensitivity and suggest a potential therapeutic use of σ₁ receptor antagonists for the management of neuropathic pain as monotherapy. Moreover, data support their use in opioid adjuvant therapy: combination of σ₁ receptor antagonists and opioids results in potentiation of opioid analgesia, without significant increases in opioid-related unwanted effects. Results from clinical trials using selective σ₁ receptor antagonists in several pain conditions are eagerly awaited to ascertain the potential of σ₁ receptor modulation in pain therapy.

Keywords: Analgesia; Neuropathic; Opioid; Pain; Sensitization; Sigma 1 receptor.

Publication types

  • Review

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Humans
  • Molecular Targeted Therapy / methods*
  • Nociception / drug effects
  • Pain / drug therapy*
  • Pain / metabolism
  • Pain / psychology
  • Receptors, sigma / antagonists & inhibitors
  • Receptors, sigma / metabolism*


  • Analgesics
  • Receptors, sigma
  • sigma-1 receptor