Hanyang Med Rev.  2011 May;31(2):123-133. 10.7599/hmr.2011.31.2.123.

Role of Sigma Receptor and Neurosteroids in Pain Sensation

• Lee JH

• KMID: 2168189
• DOI: http://doi.org/10.7599/hmr.2011.31.2.123

Abstract

The sigma-1 receptor has recently been implicated in a myriad of cellular functions and biological processes. Previous studies have demonstrated that the spinal sigma-1 receptor plays a pro-nociceptive role in acute pain and that the direct activation of sigma-1 receptor enhances the nociceptive response to peripheral stimuli, which is closely associated with calcium-dependent second messenger cascades including protein kinase C (PKC). In addition, the activation of sigma-1 receptor increases PKC- and protein kinase alpha (PKA)-dependent phosphorylation of the N-Methyl- D-aspartate (NMDA) receptor in the spinal cord, which results in the potentiation of intrathecal NMDA-evoked spontaneous pain behavior. Moreover, the blockade of spinal sigma-1 receptor suppresses the development of neuropathic pain and blocks the increase of phosphorylation of extracellular signal-regulated kinase (ERK) as well as pNR1 in the spinal cord. Recently, it was also reported that spinal neurosteroids such as pregnenolone and dehydroepiandrosterone sulfate, which are recognized as endogenous ligands for sigma-1 receptor, could produce mechanical hypersensitivity via sigma-1 receptor-mediated increase of pNR1. Collectively, these findings demonstrate that the activation of spinal sigma-1 receptor or the increase of neurosteroids is closely associated with the acute pain sensation or the development of chronic pain, and imply that sigma-1 receptor can be a new potential target for the development of analgesics.

Keyword

Sigma-1 receptor; Neurosteroids; Chronic pain; Central sensitization; N-Methyl-D-aspartate (NMDA) receptor

MeSH Terms

Acute Pain
Analgesics
Biological Processes
Central Nervous System Sensitization
Chronic Pain
D-Aspartic Acid
Dehydroepiandrosterone Sulfate
Hypersensitivity
Ligands
Neuralgia
Neurotransmitter Agents
Phosphorylation
Phosphotransferases
Pregnenolone
Protein Kinase C
Protein Kinases
Receptors, sigma
Second Messenger Systems
Sensation
Spinal Cord
Analgesics
D-Aspartic Acid
Dehydroepiandrosterone Sulfate
Ligands
Neurotransmitter Agents
Phosphotransferases
Pregnenolone
Protein Kinase C
Protein Kinases
Receptors, sigma

Figure

• 

  Fig. 1 Possible mechanism for the action of sigma-1 receptor in pain sensation. NS, neurosteroids.

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