Abstract
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.
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