Capsaicin infused into the PAG affects rat tail flick responses to noxious heat and alters neuronal firing in the RVM
Capsaicin infused into the PAG affects rat tail flick responses to noxious heat and alters neuronal firing in the RVM
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DOI：
10.1152/jn.00433.2003
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发表时间：
2003-10-01
影响因子：
2.5
通讯作者：
Jarvis, MF
中科院分区：
文献类型：
--
作者：
McGaraughty, S;Chu, KL;Jarvis, MF
众所周知，香草素受体VR1是一种重要的外周伤害性感受介质。VR1受体也位于大脑的几个区域，但尚不确定这些棘上VR1受体是否对伤害性感受系统有任何影响。在中脑导水管周围灰质的背侧(DPAG)或腹侧(VPAG)区微量注射辣椒素(10nmol/0.4mul)，研究VR1受体在脊髓上的伤害性感受作用。本实验观察了辣椒素对轻麻醉大鼠头端腹内侧延髓(RVM)甩尾潜伏期(浸泡在52℃水中)和神经元活动(开、关细胞和中性细胞)的影响。在DPAG内注射辣椒素，但不在VPAG内注射辣椒素，可引起最初的痛敏反应，随后出现镇痛(注射后125+/-20.96分钟)。与甩尾相关的ON细胞活动爆发在痛觉过敏阶段较早被触发，而在止痛阶段延迟或消失。ON细胞的自发活动在痛觉敏期开始时增加，在止痛期之前和期间降低。在痛觉过敏阶段，这些细胞与甩尾相关的细胞外活动暂停和自发放电没有变化。在止痛期，外周细胞在伤害性刺激时不再停顿，自发活动水平增加。中性细胞的激活在这两个阶段都没有受到影响。DPAG内预先注入VR1受体拮抗剂辣椒素(10nmo1/0.4mul)可阻断辣椒素引起的痛敏反应以及相应的细胞内外活动的变化。未处理组大鼠DPAG内可见VR1受体免疫染色。微量注射辣椒素可能使DPAG神经元敏化，然后减敏，影响伤害性反射和RVM神经元的活动。这些结果表明，DPAG中的棘上VR1受体参与了伤害性感觉的下行调制。
It is well established that the vanilloid receptor, VR1, is an important peripheral mediator of nociception. VR1 receptors are also located in several brain regions, yet it is uncertain whether these supraspinal VR1 receptors have any influence on the nociceptive system. To investigate a possible nociceptive role for supraspinal VR1 receptors, capsaicin (10 nmol in 0.4 mul) was microinjected into either the dorsal (dPAG) or ventral (vPAG) regions of the periaqueductal gray. Capsaicin-related effects on tail flick latency (immersion in 52degreesC water) and on neuronal activity (ON-, OFF-, and neutral cells) in the rostral ventromedial medulla (RVM) were measured in lightly anesthetized rats. Administration of capsaicin into the dPAG but not the vPAG caused an initial hyperalgesic response followed later by analgesia (125 +/- 20.96 min postinjection). The tail flick-related burst in ON-cell activity was triggered earlier in the hyperalgesic phase and was delayed or absent during the analgesic phase. Spontaneous activity of ON-cells increased at the onset of the hyperalgesic phase and decreased before and during the analgesic phase. The tail flick-related pause in OFF-cell activity as well as spontaneous firing for these cells was unchanged in the hyperalgesic phase. During the analgesic phase, OFF-cells no longer paused during noxious stimulation and had increased levels of spontaneous activity. Neutral cell firing was unaffected in either phase. Pretreatment with the VR1 receptor antagonist, capsazepine (10 nmol in 0.4 mul), into the dPAG blocked the capsaicin-induced hyperalgesia as well as the corresponding changes in ON- and OFF-cell activity. VR1 receptor immunostaining was observed in the dPAG of untreated rats. Microinjection of capsaicin likely sensitized and then desensitized dPAG neurons affecting nocifensive reflexes and RVM neuronal activity. These results suggest that supraspinal VR1 receptors in the dPAG contribute to descending modulation of nociception.