Tooth pulp inflammation increases brain-derived neurotrophic factor expression in rodent trigeminal ganglion neurons.

Nociceptive pathways with first-order neurons located in the trigeminal ganglion (TG) provide sensory innervation to the head, and are responsible for a number of common chronic pain conditions, including migraines, temporomandibular disorders and trigeminal neuralgias. Many of those conditions are associated with inflammation. Yet, the mechanisms of chronic inflammatory pain remain poorly understood. Our previous studies show that the neurotrophin brain-derived neurotrophic factor (BDNF) is expressed by adult rat TG neurons, and released from cultured newborn rat TG neurons by electrical stimulation and calcitonin gene-related peptide (CGRP), a well-established mediator of trigeminal inflammatory pain. These data suggest that BDNF plays a role in activity-dependent plasticity at first-order trigeminal synapses, including functional changes that take place in trigeminal nociceptive pathways during chronic inflammation. The present study was designed to determine the effects of peripheral inflammation, using tooth pulp inflammation as a model, on regulation of BDNF expression in TG neurons of juvenile rats and mice. Cavities were prepared in right-side maxillary first and second molars of 4-week-old animals, and left open to oral microflora. BDNF expression in right TG was compared with contralateral TG of the same animal, and with right TG of sham-operated controls, 7 and 28 days after cavity preparation. Our ELISA data indicate that exposing the tooth pulp for 28 days, with confirmed inflammation, leads to a significant upregulation of BDNF in the TG ipsilateral to the affected teeth. Double-immunohistochemistry with antibodies against BDNF combined with one of nociceptor markers, CGRP or TRPV1, revealed that BDNF is significantly upregulated in TRPV1-immunoreactive (IR) neurons in both rats and mice, and CGRP-IR neurons in mice, but not rats. Overall, the inflammation-induced upregulation of BDNF is stronger in mice compared to rats. Thus, mouse TG provides a suitable model to study molecular mechanisms of inflammation-dependent regulation of BDNF expression in vivo.

痛觉传导通路的一级神经元位于三叉神经节（TG），为头部提供感觉神经支配，并与许多常见的慢性疼痛病症有关，包括偏头痛、颞下颌关节紊乱和三叉神经痛。其中许多病症与炎症有关。然而，慢性炎症性疼痛的机制仍知之甚少。我们之前的研究表明，神经营养因子脑源性神经营养因子（BDNF）由成年大鼠的TG神经元表达，并且可通过电刺激以及降钙素基因相关肽（CGRP，一种已确定的三叉神经炎性疼痛介质）从培养的新生大鼠TG神经元中释放。这些数据表明，BDNF在一级三叉神经突触的活动依赖性可塑性中起作用，包括慢性炎症期间三叉神经痛觉传导通路中发生的功能变化。本研究旨在以牙髓炎症为模型，确定外周炎症对幼年大鼠和小鼠TG神经元中BDNF表达的调节作用。在4周龄动物右侧上颌第一和第二磨牙制备龋洞，并使其暴露于口腔微生物群。在龋洞制备7天和28天后，将右侧TG中的BDNF表达与同一动物对侧的TG以及假手术对照组的右侧TG进行比较。我们的酶联免疫吸附测定（ELISA）数据表明，牙髓暴露28天（已证实有炎症）会导致患牙同侧TG中的BDNF显著上调。用抗BDNF抗体与一种痛觉感受器标记物（CGRP或TRPV1）进行双重免疫组织化学分析显示，在大鼠和小鼠的TRPV1免疫反应性（IR）神经元以及小鼠（而非大鼠）的CGRP - IR神经元中，BDNF显著上调。总体而言，与大鼠相比，炎症诱导的BDNF上调在小鼠中更为明显。因此，小鼠TG为研究体内炎症依赖性BDNF表达调节的分子机制提供了一个合适的模型。