Contribution of α2A-adrenoceptor subtype to effect of dexmedetomidine and xylazine on spinal synaptic transmission of mice

Abstract

Alpha-2A adrenergic receptor (AR) subtype plays an important role in the analgesic effect of α2-AR agonists. Here, we examined the effects of α2-AR agonists, dexmedetomidine and xylazine, on spinal synaptic transmission in newborn C57BL/6J and α2A-AR mutant mice. Spinal reflex potentials, the monosynaptic reflex potential (MSR) and the slow ventral root potential (sVRP), were measured in isolated spinal cords. The compound action potential was measured in isolated lumbar nerve. Dexmedetomidine and xylazine suppressed both the MSR and sVRP in a concentration-dependent manner. In α2A-AR mutant mice, sVRP suppression by dexmedetomidine was greatly weakened, while that by xylazine (30-100μM) showed only slight attenuation. A high concentration (300μM) of xylazine completely suppressed the sVRP, even in α2A-AR mutant mice spinal cords, and also suppressed the compound action potential. MSR suppression by these α2-AR agonists had no difference between wild-type and α2A-AR mutant mice. These results suggest that sVRP suppression by dexmedetomidine and xylazine is mainly mediated by α2A-AR. In addition, a high concentration of xylazine inhibits conduction of the action potential, which is not mediated by α2A-AR. α2-AR is not responsible for the dexmedetomidine- and xylazine-mediated inhibition of the MSR.

Dexmedetomidine as adjuvant to lower doses of intrathecal bupivacaine for lower limb orthopedic surgeries

“…Intrathecal α 2 agonists potentiates the effects of local anesthetics and allow a decrease in dose without respiratory depression and hemodynamic instability. Dexmedetomidine is believed to act at the spinal[ 8 ] and supraspinal receptors. [ 9 ] Compared to its counterpart, clonidine, it has 8-fold greater affinity for α2 receptors.…”

Comparative Study between Intrathecal Bupivacaine and Intrathecal Bupivacaine with Dexmedetomidine as an Adjuvant

“…The drug acts at spinal & supraspinal level. [10,11] As compared clonidine, it has 8-times affinity for α 2 receptors. Hence, when used as an adjuvant to local anesthetics, it leads to sensory and motor block for longer duration and reduces need for analgesic requirements.…”

The α2A‐adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine

“…Our previous study using electrophysiological approaches also showed that the inhibitory effect of high concentrations of xylazine on nociceptive synaptic transmission is retained in isolated spinal cords of D79N mice and that xylazine inhibits the spinal nerve conduction of action potentials in an α 2A ‐AR‐independent manner. (Kobayashi, Otsuguro, Yamaguchi, & Ito, ). These α 2A ‐AR‐independent mechanisms seem to have less contribution to the clinical effects, at least, by intraperitoneally injected xylazine, since xylazine had no effects on D79N mice.…”