α2-adrenergic receptors in human dorsal root ganglia -: Predominance of α2b and α2c subtype mRNAs

Background: Nonselective alpha(2)-adrenergic receptor (alpha(2)AR) agonists (e.g., clonidine) mediate antinociception in part through alpha(2)ARs in spinal cord dorsal horn; however, use of these agents for analgesia in humans is limited by unwanted sedation and hypotension. The authors previously demonstrated alpha(2) approximate to alpha(2b) >>> alpha(2c) mRNA in human spinal cord dorsal horn cell bodies. However, because 20% of dorsal horn alpha(2)ARs derive from cell bodies that reside in the associated dorsal root ganglion (DRG), it is important to evaluate alpha(2)AR expression in this tissue as well. Therefore, the authors evaluated the hypothesis that alpha(2b) mRNA, alpha(2c) mRNA, or both are present in human DRG. Methods: Molecular approaches were used to determine alpha(2)AR expression in 28 human DRGs because of low overall receptor mRNA expression and small sample size. After creation of synthetic competitor cDNA and establishment of amplification conditions with parallel efficiencies, competitive reverse transcription polymerase chain reaction was performed using RNA isolated from human DRG. Results: Overall expression of alpha(2)AR mRNA in DRG is low but reproducible at all spinal levels, alpha(2b) and alpha(2c)AR subtype mRNAs predominate (alpha(2b) approximate to alpha(2c)), accounting for more than 95% of the total alpha(2)AR mRNA in DRG at all human spinal nerve root levels. Conclusions: Predominance of alpha(2b) and alpha(2c)AR mRNA in human DRG is distinct from alpha(2)AR mRNA expression in cell bodies originating in human spinal cord dorsal horn, where alpha(2a) and alpha(2b) predominate with little or absent alpha(2c) expression. These findings also highlight species heterogeneity in alpha(2)AR expression in DRG. If confirmed at a protein level, these findings provide an additional step in unraveling mechanisms involved in complex neural pathways such as those for pain.