Hohmann A G, Tsou K, Walker J M
Schrier Research Laboratory, Department of Psychology, Brown University Providence, Rhode Island 02912, USA.
J Neurophysiol. 1999 Feb;81(2):575-83. doi: 10.1152/jn.1999.81.2.575.
The effects of cannabinoid agonists on noxious heat-evoked firing of 62 spinal wide dynamic range (WDR) neurons were examined in urethan-anesthetized rats (1 cell/animal). Noxious thermal stimulation was applied with a Peltier device to the receptive fields in the ipsilateral hindpaw of isolated WDR neurons. To assess the site of action, cannabinoids were administered systemically in intact and spinally transected rats and intraventricularly. Both the aminoalkylindole cannabinoid WIN55,212-2 (125 microg/kg iv) and the bicyclic cannabinoid CP55,940 (125 microg/kg iv) suppressed noxious heat-evoked activity. Responses evoked by mild pressure in nonnociceptive neurons were not altered by CP55,940 (125 microg/kg iv), consistent with previous observations with another cannabinoid agonist, WIN55,212-2. The cannabinoid induced-suppression of noxious heat-evoked activity was blocked by pretreatment with SR141716A (1 mg/kg iv), a competitive antagonist for central cannabinoid CB1 receptors. By contrast, intravenous administration of either vehicle or the receptor-inactive enantiomer WIN55,212-3 (125 microg/kg) failed to alter noxious heat-evoked activity. The suppression of noxious heat-evoked activity induced by WIN55,212-2 in the lumbar dorsal horn of intact animals was markedly attenuated in spinal rats. Moreover, intraventricular administration of WIN55,212-2 suppressed noxious heat-evoked activity in spinal WDR neurons. By contrast, both vehicle and enantiomer were inactive. These findings suggest that cannabinoids selectively modulate the activity of nociceptive neurons in the spinal dorsal horn by actions at CB1 receptors. This modulation represents a suppression of pain neurotransmission because the inhibitory effects are selective for pain-sensitive neurons and are observed with different modalities of noxious stimulation. The data also provide converging lines of evidence for a role for descending antinociceptive mechanisms in cannabinoid modulation of spinal nociceptive processing.
在乌拉坦麻醉的大鼠（每只动物1个细胞）中，研究了大麻素激动剂对62个脊髓广动力范围（WDR）神经元的伤害性热诱发放电的影响。使用珀耳帖装置对分离出的WDR神经元同侧后爪的感受野施加伤害性热刺激。为了评估作用部位，在完整和脊髓横断的大鼠中全身给药大麻素，并进行脑室内给药。氨基烷基吲哚大麻素WIN55,212-2（静脉注射125μg/kg）和双环大麻素CP55,940（静脉注射125μg/kg）均抑制了伤害性热诱发的活动。CP55,940（静脉注射125μg/kg）未改变非伤害性神经元中轻度压力诱发的反应，这与先前使用另一种大麻素激动剂WIN55,212-2的观察结果一致。大麻素诱导的对伤害性热诱发活动的抑制作用可被中枢大麻素CB1受体的竞争性拮抗剂SR141716A（静脉注射1mg/kg）预处理所阻断。相比之下，静脉注射溶剂或受体无活性对映体WIN55,212-3（125μg/kg）未能改变伤害性热诱发的活动。在完整动物的腰段背角中，WIN55,212-2诱导的对伤害性热诱发活动的抑制作用在脊髓大鼠中明显减弱。此外，脑室内注射WIN55,212-2可抑制脊髓WDR神经元中伤害性热诱发的活动。相比之下，溶剂和对映体均无活性。这些发现表明，大麻素通过作用于CB1受体选择性地调节脊髓背角中伤害性神经元的活动。这种调节代表了对疼痛神经传递的抑制，因为抑制作用对疼痛敏感神经元具有选择性，并且在不同的伤害性刺激模式下均能观察到。这些数据还为下行抗伤害感受机制在大麻素对脊髓伤害性处理的调节中的作用提供了多条汇聚的证据。
