Blivis D, Mentis G Z, O'donovan M J, Lev-Tov A
Dept. of Anatomy and Cell Biology, The Hebrew University Medical School, Jerusalem, 91010, Israel.
J Neurophysiol. 2007 Apr;97(4):2875-86. doi: 10.1152/jn.01313.2006. Epub 2007 Feb 7.
The effects of opioids on sacrocaudal afferent (SCA) pathways and the pattern-generating circuitry of the thoracolumbar and sacrocaudal segments of the spinal cord were studied in isolated spinal cord and brain stem-spinal cord preparations of the neonatal rat. The locomotor and tail moving rhythm produced by activation of nociceptive and nonnociceptive sacrocaudal afferents was completely blocked by specific application of the mu-opioid receptor agonist [d-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin acetate salt (DAMGO) to the sacrocaudal but not the thoracolumbar segments of the spinal cord. The rhythmic activity could be restored after addition of the opioid receptor antagonist naloxone to the experimental chamber. The opioid block of the SCA-induced rhythm is not due to impaired rhythmogenic capacity of the spinal cord because a robust rhythmic activity could be initiated in the thoracolumbar and sacrocaudal segments in the presence of DAMGO, either by stimulation of the ventromedial medulla or by bath application of N-methyl-d-aspartate/serotonin. We suggest that the opioid block of the SCA-induced rhythm involves suppression of synaptic transmission through sacrocaudal interneurons interposed between SCA and the pattern-generating circuitry. The expression of mu opioid receptors in several groups of dorsal, intermediate and ventral horn interneurons in the sacrocaudal segments of the cord, documented in this study, provides an anatomical basis for this suggestion.
在新生大鼠的离体脊髓和脑干-脊髓标本中,研究了阿片类药物对骶尾传入(SCA)通路以及脊髓胸腰段和骶尾段模式生成回路的影响。通过将μ-阿片受体激动剂[D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-脑啡肽醋酸盐(DAMGO)特异性应用于脊髓的骶尾段而非胸腰段,可完全阻断由伤害性和非伤害性骶尾传入激活产生的运动和尾巴摆动节律。在实验腔中加入阿片受体拮抗剂纳洛酮后,节律性活动可恢复。阿片类药物对SCA诱导节律的阻断并非由于脊髓节律生成能力受损,因为在存在DAMGO的情况下,通过刺激延髓腹内侧或通过浴用N-甲基-D-天冬氨酸/5-羟色胺,可在胸腰段和骶尾段引发强烈的节律性活动。我们认为,阿片类药物对SCA诱导节律的阻断涉及通过插入SCA和模式生成回路之间的骶尾中间神经元抑制突触传递。本研究记录的脊髓骶尾段几组背角、中间角和腹角中间神经元中μ阿片受体的表达为这一观点提供了解剖学基础。