α2-Adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding α2-adrenergic receptor subtypes at four distinct levels

Abstract

alpha 2-Adrenergic receptor (AR) subtype mRNA (alpha 2a, alpha 2b, alpha 2c) neuronal localization in human spinal cord has not been described. We therefore performed in situ hybridization to identify cell bodies at four levels of human spinal cord (cervical, thoracic, lumbar, sacral) containing alpha 2AR subtype specific mRNA. alpha 2AR mRNA is present in gray matter only (ventral > dorsal; sacral > cervical > thoracic = lumbar). In addition to alpha 2AR mRNA in cell bodies in thoracic and lumbar intermediolateral (sympathetic) and sacral intermediate (parasympathetic) cell columns (lamina VII), all levels in dorsal horn laminae I, II, V, and ventral horn lamina IX, we demonstrate alpha 2AR mRNA in dorsal horn laminae III and IV, and dorsal nucleus of Clarke, where alpha 2ARs have not been described. Previously unreported heterogeneity in alpha 2AR subtype distribution (alpha 2a and alpha 2bAR mRNA present, alpha 2cAR mRNA virtually absent) is found at all sites of alpha 2AR mRNA expression in human spinal cord, including locations known to mediate effects of alpha 2AR agonist drugs on nociception, autonomic function and motor tone. Cervical spinal cord demonstrates a predominance of alpha 2a mRNA signal, while thoracic, lumbar, and sacral spinal cord demonstrate an increasing predominance of alpha 2bAR mRNA. If confirmed at a protein level, these findings have profound implications for therapeutic strategies in managing human pain.

Mode of action of α-adrenoceptor antagonists in the treatment of lower urinary tract symptoms

“…It was speculated that in addition to the antagonistic action of these agents on the α 1 α-ARs of prostatic smooth muscle, both agents (especially naftopidil) also may act on the lumbosacral cord (α 1 δ-ARs?). This observation is of particular interest considering the findings that in the human spinal cord, α 1 δ-AR mRNA predominated overall [34]. However, the distribution of spinal α 1 -AR mRNA subtypes in rat and human spinal cord may not be the same [32].…”

“…α 1 -AR mRNA is widely distributed in the brain and spinal cord [32][33][34] and noradrenergic neurons in the brain stem project to the autonomic and somatic nuclei in the lumbosacral spinal cord [35,36]. Bladder and urethral activation through these pathways may involve excitatory α 1 -ARs, which seem to be tonically active in the sympathetic and somatic neural control of the lower urinary tract [36].…”

Alpha-Blockers and Intraoperative Floppy Iris Syndrome: Ophthalmic Adverse Events Following Cataract Surgery

“…Within the genitourinary system, α 1D -adrenergic receptors are mainly located in the bladder body and dome [12]. α 1D -receptors are also located in the spinal cord, where they are presumed to play a role in the sympathetic modulation of parasympathetic activity [13].…”

The role of the prostatic stroma in chronic prostatitis/chronic pelvic pain syndrome

“…Thus, the action in the central nervous system could increase bladder capacity and decrease the sensation to void, thereby affecting nocturia and the feeling of incomplete emptying. Furthermore, in the human spinal cord, mRNA encoding each of the three a 1 AR subtypes has been demonstrated and localizes to ventral gray matter, with a 1D ARs predominating compared to the other subtypes [41].…”