H1 Receptor-Expressing Afferent Neurons After Peripheral Axotomy and Naturopathic Pain.

药理学研究表明，初级感觉神经元的一个亚群通过HI受体对组胺产生反应。然而，哪种类型的初级感觉神经元表达HI受体尚不清楚。我们用豚鼠H1受体基因的cRNA探针原位杂交组织化学的方法解决了这个问题。在三叉神经节和腰背根神经节(DRG)神经元中，约有15%~20%的神经元表达H1受体，而结状神经节神经元中无表达。DRG内的阳性神经元体积较小，并用异凝素B4标记，表明这些神经元有无髓纤维。然而，表达H1受体基因的DRG神经元对参与初级感觉系统伤害性传递的SP或CGRP不呈免疫反应。此外，辣椒素(50 mg/kg)对新生豚鼠背根神经节有少量CGRP免疫阳性神经元，但其H1受体表达神经元的百分率(15%~20%)和表达信号强度不受辣椒素的影响，提示表达H1受体的神经元对辣椒素不敏感。这些发现表明，H1受体表达的神经元参与了一种独特的感觉方式的传递，如瘙痒。坐骨神经挤压伤后1~5天，背根神经节mRNA阳性神经元数量明显增加。这些神经元在神经挤压后转为mRNA阳性的神经元也以小神经元为主。与正常情况相反，在许多肽能(SP/CGRP)神经元中检测到了mRNA信号。另一方面，正常情况下表现为强标记的神经元中的mRNA信号减少。这些结果提示，损伤传入神经元HI受体基因表达上调可能参与了神经病理性疼痛的发生。

Pharmacological studies have suggested that a subgroup of primary sensory neurons is responsive to histamine via HI receptor. However, which type of primary sensory neurons express HI receptor is not known. We addressed this issue using in situ hybridization histochemistry with a cRNA probe for the guinea pig H1 receptor mRNA. H1 receptor mRNA was expressed in about 15-20% of the trigeminal and lumbar dorsal root ganglion(DRG) neurons, but none of nodose ganglion neurons. The positive neurons in DRG were exclusively small in size, and were labeled by isolectin B4, suggesting that these neurons have unmyelinated fibers. However, H1 receptor mRNA-expressing DRG neurons were not immunoreaetive to SP or CGRP, which are implicated in the nociceptive transmission of the primary sensory system. Moreover, in guinea pigs neonatally treated with capsaicin(50mg/kg), few CGRP-immunoreaetive neurons were seen in DRG, but the percentage of H1 receptor mRNA-expressing neurons(15%-20%) and the intensity of the mRNA signals in these neurons were not affected by neonatal capsaicin treatment, suggesting that H1 receptor-expressing neurons are not sensitive to capsaicin. These findings suggest that H1 receptor-expressing neurons are involved in the transmission of a unique sensory modality such as itch. A marked increase in the number of mRNA-positive DRG neurons was observed 1-5 days after a crush injury of the sciatic nerve. These neurons turned mRNA-positive after the nerve crush were also mainly small-sized., The mRNA signals were detected in many peptidergic(SP/CGRP) neurons, in contrast to the normal condition. On the other hand, mRNA signals were decreased in the neurons which showed intense labeling in the normal condition. These results suggest that the gene expression of HI receptors up-regulated in injured afferents may be involved in neuropathic pain.