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 des cribed. 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 interme diate (parasympathetic) cell columns (lamina VII), all levels in dorsa l horn laminae I, II, V, and ventral horn lamina IX, we demonstrate al pha(2)AR mRNA in dorsal horn laminae III and IV, and dorsal nucleus of Clarke, where gamma(2)ARs have not been described. Previously unrepor ted heterogeneity in alpha(2)AR subtype distribution (alpha(2a) and al pha(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, includi ng locations known to mediate effects of alpha(2)AR agonist drugs on n ociception, autonomic function and motor tone. Cervical spinal cord de monstrates a predominance of alpha(2a) mRNA signal, while thoracic, lu mbar, and sacral spinal cord demonstrate an increasing predominance of alpha(2b)AR mRNA. If confirmed at a protein level, these findings hav e profound implications for therapeutic strategies in managing human p ain.