Wang X M, Yan J Q, Zhang K M, Mokha S S
Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA.
Brain Res. 1996 Nov 11;739(1-2):235-43. doi: 10.1016/s0006-8993(96)00828-1.
This report describes the effects of intravenously administered agonists and antagonists at mu-, delta 1- and delta 2-opioid receptors on the A delta- and C-fiber-evoked responses of trigeminal nociceptive neurons in anesthetized rats. Extracellular single unit recordings were made from 61 nociceptive neurons (23 NS, 38 WDR) in the superficial and 37 nociceptive neurons (3 NS, 34 WDR) in the deeper dorsal horn of the medulla (trigeminal nucleus caudalis). Administration of either the delta 1-receptor agonist [D-Pen2,5]enkephalin (DPDPE; 0.05-2 mg/kg), the delta 2-receptor agonist [D-Ala2, Glu4]deltorphin (DELT; 1-2 mg/kg) or the mu-receptor agonist [D-Ala2, N-MePhe4, Gly5-ol]enkephalin (DAMGO; 0.05-1 mg/kg) inhibited the A delta- and C-fiber-evoked responses of nociceptive neurons in the superficial and deeper dorsal horn. The inhibitory effect was more pronounced on the C-fiber-evoked responses than on the A delta-fiber-evoked responses. In other neurons, DPDPE also produced facilitation, or inhibition followed by facilitation, or differential effects (inhibition of the C-fiber-evoked responses and facilitation of the A delta-fiber-evoked responses) on the A delta- and C-fiber-evoked responses. The effects of DPDPE were antagonized by 7-benzylidenenaltrexone (BNTX, 0.4-1 mg/kg), a delta 1-receptor antagonist, in 88% (7/8) of neurons. Naltriben (NTB, 0.7-1 mg/kg), a delta 2-receptor antagonist, antagonized the effect of both DELT and DPDPE. A smaller dose of NTB (0.3 mg/kg), which failed to reverse the effects of DPDPE in 100% (4/4) of neurons, effectively antagonized the effects of DELT in 100% (6/6) of neurons. The inhibitory action of DAMGO was completely antagonized by naloxone (0.2 mg/kg) in 100% (6/6) of neurons. The results of the present investigation suggest that: (1) mu-, delta 1- and delta 2-opioid receptors play an important role in the inhibitory modulation of the A delta- and C-fiber-evoked responses of nociceptive neurons in the superficial and deeper dorsal horn of the medulla; (2) selective inhibition of the C-fiber-evoked responses by activation of opioid receptors may account for the opioid-mediated selective suppression of second or persistent pain as compared to first pain; and (3) NTB, in a limited dose range, can discriminate between delta 1- and delta 2-opioid receptor subtypes.
本报告描述了静脉注射μ-、δ1-和δ2-阿片受体激动剂和拮抗剂对麻醉大鼠三叉神经伤害性神经元Aδ纤维和C纤维诱发反应的影响。对延髓（三叉神经尾核）浅部的61个伤害性神经元（23个NS神经元、38个WDR神经元）和深部背角的37个伤害性神经元（3个NS神经元、34个WDR神经元）进行了细胞外单单位记录。给予δ1受体激动剂[D-Pen2,5]脑啡肽（DPDPE；0.05 - 2 mg/kg）、δ2受体激动剂[D-Ala2, Glu4]强啡肽（DELT；1 - 2 mg/kg）或μ受体激动剂[D-Ala2, N-MePhe4, Gly5-ol]脑啡肽（DAMGO；0.05 - 1 mg/kg）可抑制浅部和深部背角伤害性神经元的Aδ纤维和C纤维诱发反应。对C纤维诱发反应的抑制作用比对Aδ纤维诱发反应更明显。在其他神经元中，DPDPE对Aδ纤维和C纤维诱发反应还产生易化作用，或先抑制后易化，或产生不同效应（抑制C纤维诱发反应而易化Aδ纤维诱发反应）。在88%（7/8）的神经元中，δ1受体拮抗剂7-苄叉基纳曲酮（BNTX，0.4 - 1 mg/kg）可拮抗DPDPE的作用。δ2受体拮抗剂纳曲苄（NTB，0.7 - 1 mg/kg）可拮抗DELT和DPDPE的作用。较小剂量的NTB（0.3 mg/kg）不能完全拮抗DPDPE的作用（100%，4/4），但能完全拮抗DELT的作用（100%，6/6）。在100%（6/6）的神经元中，纳洛酮（0.2 mg/kg）可完全拮抗DAMGO的抑制作用。本研究结果表明：（1）μ-、δ1-和δ2-阿片受体在延髓浅部和深部背角伤害性神经元Aδ纤维和C纤维诱发反应的抑制性调制中起重要作用；（2）与第一痛相比，阿片受体激活对C纤维诱发反应的选择性抑制可能解释了阿片介导的对第二痛或持续性痛的选择性抑制；（3）在有限剂量范围内，NTB可区分δ1和δ2阿片受体亚型。
