et al., 2000).Īfter peripheral nerve injury, there is a decrease in alpha 2A mRNA and protein immunoreactivity in the spinal cord of the rat ( Stone, L. The alpha 2B adrenoceptors may play an important role in the pontine noradrenergic nuclei involved in analgesic action of nitrous oxide ( Sawamura, S. The alpha 2C adrenoceptors have been shown to be involved in spinal analgesia and adrenergic–opioid synergy ( Fairbanks, C. J., 2003), suggesting a role in postsynaptic modulation. However, alpha 2C adrenoceptor-bearing terminals synapse with NK-1 projection cells in the rat dorsal horn ( Olave, M. Most studies support a role for the alpha 2A subtype in spinal analgesia ( Hunter, J. Studies using transgenic mice, such as D79N mice with a point mutation of the alpha 2A adrenoceptors, have examined the subtypes of spinal alpha 2 adrenoceptors involved in descending inhibition.
In vivo whole-cell patch-clamp recordings from rat substantia gelatinosa neurons show that NA reduces EPSC and suppresses action potentials evoked by a noxious stimulus, an effect that is blocked by antagonism of alpha 2, but not alpha 1, adrenoceptors ( Sonohata, M. et al., 1980), and may involve both pre- and postsynaptic mechanisms ( Sonohata, M. The antinociceptive effect of NA in the spinal cord does not appear to require GABAergic, glycinergic, opioidergic, and serotonergic activity ( Reddy, S. Intrathecal administration of the adrenoceptor antagonists produces a decrease in nociceptive threshold in the rat, suggesting that the descending noradrenergic system is tonically active ( Sagen, J. Opioid analgesia is enhanced in norepinephrine transporter knockout mice and the effect is blocked by yohimbine ( Bohn, L. Consistently, depletion of spinal NA by 6-hydroxydopamine decreases and intrathecal NA elevates the nociceptive threshold ( Reddy, S. These results clearly indicate a role of spinopetal noradrenergic fibers in descending modulation since there are no noradrenaline-producing cell bodies in the spinal cord ( Swanson, L. Selective depletion of spinal noradrenaline by intrathecal DSP4 attenuates morphine analgesia ( Zhong, F. The PAG-produced inhibition of dorsal horn neurons is reduced by microdialysis of alpha 2 adrenoceptor antagonists idazoxan and yohimbine into the dorsal horn ( Peng, Y. Intrathecal administration of the alpha 2-adrenoceptor antagonist yohimbine, but not the nonselective opioid receptor antagonist naloxone and alpha 1 adrenoceptor antagonist prazosin, attenuates descending inhibition of nocifensive tail flick reflex produced by focal stimulation of the LC/SC region ( Jones, S. Dubner, in The Senses: A Comprehensive Reference, 2008 5.49.2.2.2.(i) Noradrenaline
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