ALPHA(2)-ADRENERGIC RECEPTORS IN HUMAN SPINAL-CORD - SPECIFIC LOCALIZED EXPRESSION OF MESSENGER-RNA ENCODING ALPHA(2)-ADRENERGIC RECEPTOR SUBTYPES AT 4 DISTINCT LEVELS

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(2)AR subtype specific mRNA. alpha(2)AR mRNA is present in gray matter only (ventral > dorsal; sacral > cervical > thoracic = lumbar). In addition to alpha(2)AR 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(2)AR mRNA in dorsal horn laminae III and IV, and dorsal nucleus of Clarke, where gamma(2)ARs have not been described. Previously unreported heterogeneity in alpha(2)AR subtype distribution (alpha(2a) and alpha(2b)AR mRNA present, alpha(2c)AR mRNA virtually absent) is found at all sites of alpha(2)AR mRNA expression in human spinal cord, including locations known to mediate effects of alpha(2)AR 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(2b)AR mRNA. If confirmed at a protein level, these findings have profound implications for therapeutic strategies in managing human pain.