@entity2819 ( @entity46188 ) is a glucocorticoid produced by adrenal glands under the control of the @entity2339 . Circulating @entity46188 can enter the central nervous system and be reduced to neuroactive 3a5a-reduced @entity230 , which modulate GABAA receptors. In the dorsal spinal cord, GABAergic transmission modulates integration of nociceptive information. It has been shown that enhancing spinal inhibitory transmission alleviates @entity1931 and @entity1931 . Therefore, the spinal neuronal network is a pivotal target to counteract @entity158 symptoms. Thus, any increase in spinal 3a5a-reduced @entity134 production enhancing GABAergic inhibition should reduce nociceptive message integration and the @entity158 response. Previously, it has been shown that high levels of plasma glucocorticoids give rise to @entity1337 . However, to our knowledge, nothing has been reported regarding direct non-genomic modulation of neuronal spinal activity by peripheral @entity46188 . In the present study, we used combined in vivo and in vitro electrophysiology approaches, associated with measurement of nociceptive mechanical sensitivity and plasma @entity46188 level measurement, to assess the impact of circulating @entity46188 on @entity35 nociception. We showed that @entity46188 plasma level elevation produced @entity1337 via a reduction in @entity7183 -mediated spinal responses. In the spine, @entity46188 is reduced to the neuroactive metabolite @entity27860 , which specifically enhances lamina II GABAergic synaptic transmission. The main consequence is a reduction in lamina II network excitability, reflecting a selective decrease in the processing of nociceptive inputs. The depressed neuronal activity at the spinal level then, in turn, leads to weaker nociceptive message transmission to supraspinal structures and hence to alleviation of @entity158 .

@entity2819 @entity1337 is mediated by the spinal production of neuroactive metabolites that enhance GABAergic inhibitory transmission on dorsal horn XXXX neurons.

@entity1931 :: ('MESH:D006930', 'Disease') :: ['hyperalgesia', 'allodynia'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity46188 :: ('25305(Tax:10116)', 'Gene') :: ['CORT'] @entity1337 :: ('MESH:D000699', 'Disease') :: ['analgesia'] @entity2819 :: ('MESH:D003345', 'Chemical') :: ['Corticosterone'] @entity134 :: ('CHEBI:35341', 'Chemical') :: ['steroid'] @entity7183 :: ('10185', 'Species') :: ['C-fiber'] @entity2339 :: ('MESH:D007029', 'Disease') :: ['hypothalamic-pituitary-adrenal axis'] @entity158 :: ('MESH:D010146', 'Disease') :: ['pain'] @entity230 :: ('MESH:D013256', 'Chemical') :: ['steroids'] @entity27860 :: ('MESH:C009413', 'Chemical') :: ['allotetrahydrodeoxycorticosterone']
@entity35 :: (10116,Species) :: ['rat']
