Interdisciplinary Center for Neuronal Computation, The Edmond and Lily Safra Center for Brain Sciences, Israel.
Exp Neurol. 2012 Jul;236(1):103-11. doi: 10.1016/j.expneurol.2012.04.005. Epub 2012 Apr 19.
Spontaneous pain is difficult to measure in animals. One proposed biomarker of spontaneous pain is autotomy, a behavior frequently observed in rats with complete hindpaw denervation (the neuroma model of neuropathic pain). A large body of evidence suggests that this behavior reflects spontaneous dysesthesic sensations akin to phantom limb pain or anesthesia dolorosa. After partial paw denervation, such as in the spared nerve injury (SNI) model of neuropathic pain, autotomy is rare. Does this mean that spontaneous pain is absent? We denervated hindpaws in two stages: SNI surgery completed 7 or 28 days later by transection of the saphenous and sural nerves (SaSu). Minimal autotomy was evoked by the first stage. But it started rapidly after SaSu surgery rendered the limb numb, much more rapidly than after denervation in a single stage (neuroma model). The acceleration was proportional to the delay between the two surgeries. This "priming" effect of the first surgery indicates that the neural substrate of autotomy, spontaneous neuropathic pain, was not initiated by the onset of numbness, but rather by the first, SNI surgery. But the animal's pain experience was occult. The saphenous and sural nerves provided nociceptive sensory cover for the paw, preventing the behavioral expression of the spontaneous pain in the form of autotomy. The results support prior observations suggesting that partial nerve injury triggers spontaneous pain as well as allodynia, and illustrate the importance of nociceptive sensory cover in the prevention of self-inflicted limb injury.
自发性疼痛在动物中难以测量。一种自发疼痛的潜在生物标志物是自截，这是一种在完全后肢去神经支配（神经病理性疼痛的神经瘤模型）的大鼠中经常观察到的行为。大量证据表明，这种行为反映了自发性感觉异常，类似于幻肢痛或麻醉性疼痛。在后肢部分去神经支配后，如在 spared nerve injury (SNI) 神经病理性疼痛模型中，自截很少见。这是否意味着自发性疼痛不存在？我们分两阶段对后肢进行去神经支配：SNI 手术后 7 或 28 天通过切断隐神经和腓肠神经（SaSu）完成。第一阶段引发的自截很少。但在 SaSu 手术后，肢体麻木，自截迅速开始，比一次手术去神经支配（神经瘤模型）快得多。第一次手术的这种“启动”效应表明，自截、自发性神经病理性疼痛的神经基础不是由麻木的发生引发的，而是由第一次 SNI 手术引发的。但动物的疼痛体验是隐匿的。隐神经和腓肠神经为足部提供了伤害感受性感觉覆盖，防止了自截这种自发性疼痛的行为表达。研究结果支持了先前的观察结果，即部分神经损伤会引发自发性疼痛和痛觉过敏，并说明了伤害感受性感觉覆盖在预防自我造成的肢体损伤中的重要性。
