You Hao-Jun, Colpaert Francis C, Arendt-Nielsen Lars
Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, PR China.
Brain Res Bull. 2008 Jan 31;75(1):34-41. doi: 10.1016/j.brainresbull.2007.07.015. Epub 2007 Aug 6.
Under intact and spinalized conditions, we compared the responses of deep spinal dorsal horn (DH) nociceptive-specific (NS) and wide-dynamic range (WDR) neurons to subcutaneous bee venom (BV, 0.2 mg/50 microl)-induced persistent nociception. In contrast to the monophasic, long-lasting (34-81 min) WDR neuron responses in both intact and spinalized conditions, BV in NS neurons elicited short-term (<10 min) firing in intact, and long-term (>1 h) biphasic firing in spinalized rats. The BV-induced long-term biphasic NS neuron activities in spinalized condition consisted of a first, early phase (4-13 min) of firing occurred immediately after the BV injection, and a second phase of tonic firing that lasted for 28-74 min. The two phases were separated by a period that lasted 4-11 min during which there was very little neuronal activity. The data suggest that in the presence of peripheral nociception, a transitory (about 5-13 min) spinal segmental inhibitory control and a long-lasting descending inhibitory control govern deep spinal NS neuron but not WDR neuron activity. Previous reports assessing spinally organized motor activities showed a spinal WDR neuron well-controlled monophasic long-lasting withdrawal reflex in response to BV injection in both intact and spinalized conditions. In contrast, the current data suggest that unlike spinal WDR neurons, deep spinal DH NS neurons do not modulate spinal motor output during the persistent nociception. Using the neurokinin-1 (NK-1) receptor antagonist, L-703,606 we further found that only early (within 15 min) treatment with L-703,606 produced a significant inhibition of the enhanced mechanically evoked NS neuron responses in BV-induced nociception, suggesting a dynamic function of NK-1 receptor involvement for deep spinal NS neuron mediated central sensitisation. We conclude that deep spinal DH NS neurons are strictly governed by tonic inhibitory descending controls. As this descending inhibitory control either is absent or decays, deep spinal NS neurons may play a crucial role in the development of central sensitisation in pathological nociception, for instance in spinal cord injury-induced pathological pain.
在完整和脊髓横断条件下，我们比较了脊髓背角深层（DH）伤害性特异性（NS）和广动力范围（WDR）神经元对皮下注射蜂毒（BV，0.2 mg/50微升）诱导的持续性伤害感受的反应。与在完整和脊髓横断条件下WDR神经元呈现的单相、持久（34 - 81分钟）反应不同，BV在NS神经元中，在完整动物中引发短期（<10分钟）放电，而在脊髓横断大鼠中引发长期（>1小时）双相放电。在脊髓横断条件下，BV诱导的NS神经元长期双相活动包括，注射BV后立即出现的第一个早期阶段（4 - 13分钟）的放电，以及持续28 - 74分钟的紧张性放电的第二个阶段。这两个阶段被一个持续4 - 11分钟的时期隔开，在此期间神经元活动极少。数据表明，在存在外周伤害感受的情况下，短暂的（约5 - 13分钟）脊髓节段性抑制控制和持久的下行抑制控制支配着脊髓深层NS神经元的活动，而不是WDR神经元的活动。先前评估脊髓组织运动活动的报告显示，在完整和脊髓横断条件下，脊髓WDR神经元对BV注射有良好控制的单相持久退缩反射。相比之下，当前数据表明，与脊髓WDR神经元不同，脊髓深层DH NS神经元在持续性伤害感受期间不调节脊髓运动输出。使用神经激肽-1（NK-1）受体拮抗剂L-703,606，我们进一步发现，只有在早期（15分钟内）用L-703,606治疗，才能显著抑制BV诱导的伤害感受中机械诱发的NS神经元反应增强，这表明NK-1受体参与脊髓深层NS神经元介导的中枢敏化具有动态功能。我们得出结论，脊髓深层DH NS神经元严格受紧张性抑制性下行控制的支配。由于这种下行抑制控制要么不存在，要么减弱，脊髓深层NS神经元可能在病理性伤害感受（例如脊髓损伤诱导的病理性疼痛）的中枢敏化发展中起关键作用。
