Szallasi A, Szallasi Z, Blumberg P M
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892.
Brain Res. 1990 Dec 24;537(1-2):182-6. doi: 10.1016/0006-8993(90)90356-g.
We have previously demonstrated that resiniferatoxin functions in adult rats as an ultrapotent analog of capsaicin. In adults, capsaicin excites and then desensitizes a specific population of sensory neurons; when administered to neonates capsaicin causes degeneration of these neurons. We report here that treatment of newborn rats with resiniferatoxin caused a substantial (47%) loss of dorsal root ganglia neurons in adults and an almost complete loss of calcitonin gene related peptide-like immunoreactivity in both dorsal root ganglia and gasserian ganglia. The animals were unresponsive to noxious chemical stimuli and showed marked diminution (88%) of their neurogenic inflammatory response. Resiniferatoxin was at least 2 orders of magnitude more potent than capsaicin for inducing neurodegeneration in the neonates. Specific resiniferatoxin binding, thought to represent capsaicin receptors, decreased 80-90% in membranes from dorsal root ganglia and 50-70% in membranes from gasserian ganglia of adult rats treated neonatally with resiniferatoxin. The affinity for the residual binding decreased. We speculate that subpopulations of sensory neurons differ in susceptibility to neonatal resiniferatoxin treatment. Resiniferatoxin promises to be a useful probe to explore mechanisms of sensorotoxin-induced degeneration for subpopulations of capsaicin-sensitive sensory neurons.
我们之前已经证明，在成年大鼠中，树脂毒素作为辣椒素的一种超强效类似物发挥作用。在成年动物中，辣椒素会先兴奋然后使特定群体的感觉神经元脱敏；而给新生动物施用辣椒素会导致这些神经元退化。我们在此报告，用树脂毒素处理新生大鼠会导致成年大鼠背根神经节神经元大量（47%）丧失，并且背根神经节和三叉神经节中降钙素基因相关肽样免疫反应性几乎完全丧失。这些动物对有害化学刺激无反应，并且其神经源性炎症反应显著减弱（88%）。在诱导新生动物神经退行性变方面，树脂毒素的效力比辣椒素至少高两个数量级。被认为代表辣椒素受体的特异性树脂毒素结合，在用树脂毒素处理过新生期的成年大鼠的背根神经节膜中减少了80 - 90%，在三叉神经节膜中减少了50 - 70%。对残余结合的亲和力降低。我们推测感觉神经元的亚群对新生期树脂毒素处理的敏感性不同。树脂毒素有望成为一种有用的探针，用于探索对辣椒素敏感的感觉神经元亚群的感觉毒素诱导的退化机制。
