Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess, Medical Center and Harvard Medical School, Boston, MA 02115, USA.
Brain Behav Immun. 2012 Feb;26(2):311-7. doi: 10.1016/j.bbi.2011.09.016. Epub 2011 Oct 12.
Mast cells (MCs) are tissue resident immune cells that participate in a variety of allergic and other inflammatory conditions. In most tissues, MCs are found in close proximity to nerve endings of primary afferent neurons that signal pain (i.e. nociceptors). Activation of MCs causes the release of a plethora of mediators that can activate these nociceptors and promote pain. Although MCs are ubiquitous, conditions associated with systemic MC activation give rise primarily to two major types of pain, headache and visceral pain. In this study we therefore examined the extent to which systemic MC degranulation induced by intraperitoneal administration of the MC secretagogue compound 48/80 activates pain pathways that originate in different parts of the body and studied whether this action can lead to development of behavioral pain hypersensitivity. Using c-fos expression as a marker of central nervous system neural activation, we found that intraperitoneal administration of 48/80 leads to the activation of dorsal horn neurons at two specific levels of the spinal cord; one responsible for processing cranial pain, at the medullary/C2 level, and one that processes pelvic visceral pain, at the caudal lumbar/rostral sacral level (L6-S2). Using behavioral sensory testing, we found that this nociceptive activation is associated with development of widespread tactile pain hypersensitivity within and outside the body regions corresponding to the activated spinal levels. Our data provide a neural basis for understanding the primacy of headache and visceral pain in conditions that involve systemic MC degranulation. Our data further suggest that MC activation may lead to widespread tactile pain hypersensitivity.
肥大细胞（MCs）是组织驻留免疫细胞，参与多种过敏和其他炎症状态。在大多数组织中，MCs 与传递疼痛信号的初级传入神经元的神经末梢接近（即伤害感受器）。MC 的激活导致大量介质的释放，这些介质可以激活这些伤害感受器并促进疼痛。尽管 MC 无处不在，但与全身 MC 激活相关的条件主要引起两种主要类型的疼痛，即头痛和内脏疼痛。在这项研究中，我们因此检查了腹腔内给予 MC 分泌刺激物化合物 48/80 引起的全身性 MC 脱颗粒在多大程度上激活起源于身体不同部位的疼痛途径，并研究了这种作用是否会导致行为性疼痛过敏的发展。使用 c-fos 表达作为中枢神经系统神经激活的标志物，我们发现腹腔内给予 48/80 导致脊髓两个特定水平的背角神经元激活；一个负责处理颅痛，位于延髓/C2 水平，另一个负责处理骨盆内脏痛，位于尾腰椎/头荐骨水平（L6-S2）。使用行为感觉测试，我们发现这种伤害感受激活与对应于激活的脊髓水平的身体区域内和外部的广泛触觉疼痛过敏的发展有关。我们的数据为理解涉及全身 MC 脱颗粒的情况下头痛和内脏疼痛的首要地位提供了神经基础。我们的数据进一步表明，MC 激活可能导致广泛的触觉疼痛过敏。
