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Role of Sigma Receptor and Neurosteroids in Pain Sensation / 한양의대학술지
Hanyang Medical Reviews ; : 123-133, 2011.
Article in Korean | WPRIM | ID: wpr-19501
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.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphorylation / Phosphotransferases / Pregnenolone / Protein Kinases / Sensation / Spinal Cord / Biological Phenomena / Protein Kinase C / Second Messenger Systems / Receptors, sigma Language: Korean Journal: Hanyang Medical Reviews Year: 2011 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphorylation / Phosphotransferases / Pregnenolone / Protein Kinases / Sensation / Spinal Cord / Biological Phenomena / Protein Kinase C / Second Messenger Systems / Receptors, sigma Language: Korean Journal: Hanyang Medical Reviews Year: 2011 Type: Article