College of Dentistry Department of Orthodontics, University of Florida, Gainesville, FL, United States.
Neuroscience. 2012 Nov 8;224:294-306. doi: 10.1016/j.neuroscience.2012.08.015. Epub 2012 Aug 19.
In order to better understand and treat neuropathic pain, scientific study must use methods that can assess pain processing at the cortical level where pain is truly perceived. Operant behavior paradigms can accomplish this. We used an operant task to evaluate changes following chronic constriction injury to the trigeminal nerves. We also relate these behavioral changes to immunohistochemistry of transient receptor potential channels vanilloid 1 and melastatin 8 (TRPV1 and TRPM8) in the trigeminal ganglia. Following nerve injury, successful performance of the operant task was reduced and aversive behaviors were observed with 10 and 37 °C stimulation, indicating cold allodynia and mechanical allodynia respectively. In contrast, while aversive behaviors were observed with 48 °C stimulation, successful performance of the operant task was not substantially hindered following injury. These behavioral changes were accompanied by an increase in TRPV1 positive cells and an increased intensity of TRPM8 staining at 2 weeks post-injury, when cold allodynia is maximal. These findings suggest that the incorporation of operant behavioral assessment in the study of pain may provide insight into the relationship among peripheral changes, motivational drive, and pain. Understanding this relationship will allow us to better treat and prevent chronic neuropathic pain.
为了更好地理解和治疗神经性疼痛,科学研究必须使用能够评估皮质水平疼痛处理的方法,而疼痛正是在皮质水平被感知的。操作性行为范式可以做到这一点。我们使用操作性任务来评估慢性缩窄性三叉神经损伤后的变化。我们还将这些行为变化与三叉神经节中瞬时受体电位通道香草素 1 和 melastatin 8(TRPV1 和 TRPM8)的免疫组织化学相关联。神经损伤后,操作性任务的成功表现减少,并观察到 10 和 37°C 刺激时的厌恶行为,分别表示冷感觉过敏和机械感觉过敏。相比之下,尽管在 48°C 刺激时观察到厌恶行为,但在损伤后,操作性任务的成功表现并未受到实质性阻碍。这些行为变化伴随着 TRPV1 阳性细胞的增加和 TRPM8 染色强度的增加,在损伤后 2 周时达到冷感觉过敏的最大值。这些发现表明,在疼痛研究中纳入操作性行为评估可能会深入了解外周变化、动机驱动力和疼痛之间的关系。了解这种关系将使我们能够更好地治疗和预防慢性神经性疼痛。