| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
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.
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