Pharmacological Modulation of the Sigma 1 Receptor and the Treatment of Pain.

There is a critical need for new analgesics acting through new mechanisms of action, which could increase the efficacy with respect to existing therapies and reduce their unwanted effects. Current preclinical evidence supports the modulatory role of sigma-1 receptors (σR) in nociception, mainly based on the pain-attenuated phenotype of σR knockout mice and on the antinociceptive effect exerted by σR antagonists on pains of different etiologies. σR is highly expressed in different pain areas of the CNS and the periphery (particularly dorsal root ganglia), and interacts and modulates the functionality of different receptors and ion channels .