α2-Adrenergic receptors in human dorsal root ganglia: Predominance of α(2b) and α(2c) subtype mRNAs
Background: Nonselective α2-adrenergic receptor (α2AR) agonists (e.g., clonidine) mediate antinociception in part through α2ARs 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 α(2a) ≃ α(2b) &gt; &gt; &gt; α(2c) mRNA in human spinal cord dorsal horn cell bodies. However, because 20% of dorsal horn α2ARs derive from cell bodies that reside in the associated dorsal root ganglion (DRG), it is important to evaluate α2AR expression in this tissue as well. Therefore, the authors evaluated the hypothesis that α(2b) mRNA, α(2c) mRNA, or both are present in human DRG. Methods: Molecular approaches were used to determine α2AR 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 α2AR mRNA in DRG is low but reproducible at all spinal levels. α(2b) and α(2c)AR subtype mRNAs predominate (α(2b) ≃ α(2c)), accounting for more than 95% of the total α2AR mRNA in DRG at all human spinal nerve root levels. Conclusions: Predominance of α(2b) and α(2c)AR mRNA in human DRG is distinct from α2AR mRNA expression in cell bodies originating in human spinal cord dorsal horn, where α(2a) and α(2b) predominate with little or absent α(2c) expression. These findings also highlight species heterogeneity in α2AR 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.