Dunbar Stuart A, Karamian Ivan, Yeatman Amy, Zhang Jiahui
Department of Anesthesiology, Baystate Medical Center, Tufts University, 3400 Main Street, Springfield, MA 01199, USA.
Eur J Pharmacol. 2006 Mar 27;535(1-3):152-6. doi: 10.1016/j.ejphar.2006.02.007. Epub 2006 Mar 15.
Chronic opioid administration is associated with altered nociception. The mechanisms underlying these changes are not fully understood. Nociceptive transmission within the spinal cord is modulated by both excitatory and inhibitory neurotransmitters. Using spinal microdialysis, the effects of recurrent withdrawal on the release of gamma-aminobutyric acid (GABA), at rest or after naloxone stimulation, was investigated in rats chronically exposed to morphine. For comparison purpose, the release of glutamate was investigated in parallel. We observed that chronic morphine treatment alone significantly inhibited resting GABA release; and recurrent withdrawal appeared to reverse this effect. Recurrent withdrawal also significantly elevated resting glutamate levels. In addition, we observed that only acute withdrawal moderately increased stimulated GABA release. In contrast, both acute and recurrent withdrawal markedly increased stimulated glutamate release. These observed changes in GABA release offer direct evidence that GABA may contribute to the altered nociceptive response mediated by opioids.
长期使用阿片类药物与伤害感受改变有关。这些变化背后的机制尚未完全了解。脊髓内的伤害性传递由兴奋性和抑制性神经递质调节。采用脊髓微透析技术，研究了长期暴露于吗啡的大鼠反复戒断对静息状态下或纳洛酮刺激后γ-氨基丁酸（GABA）释放的影响。为作比较，同时研究了谷氨酸的释放。我们观察到，单独慢性吗啡治疗显著抑制静息状态下的GABA释放；反复戒断似乎可逆转这种作用。反复戒断还显著提高了静息状态下的谷氨酸水平。此外，我们观察到，只有急性戒断适度增加刺激后的GABA释放。相比之下，急性和反复戒断均显著增加刺激后的谷氨酸释放。观察到的GABA释放变化提供了直接证据，表明GABA可能参与了阿片类药物介导的伤害感受反应改变。
