Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mol Pain. 2012 Jul 9;8:52. doi: 10.1186/1744-8069-8-52.
Itch is one of the major somatosensory modalities. Some recent findings have proposed that gastrin releasing peptide (Grp) is expressed in a subset of dorsal root ganglion (DRG) neurons and functions as a selective neurotransmitter for transferring itch information to spinal cord interneurons. However, expression data from public databases and earlier literatures indicate that Grp mRNA is only detected in dorsal spinal cord (dSC) whereas its family member neuromedin B (Nmb) is highly expressed in DRG neurons. These contradictory results argue that a thorough characterization of the expression of Grp and Nmb is warranted.
Grp mRNA is highly expressed in dSC but is barely detectable in DRGs of juvenile and adult mice. Anti-bombesin serum specifically recognizes Grp but not Nmb. Grp is present in a small number of small-diameter DRG neurons and in abundance in layers I and II of the spinal cord. The reduction of dSC Grp after dorsal root rhizotomy is significantly different from those of DRG derived markers but similar to that of a spinal cord neuronal marker. Double fluorescent in situ of Nmb and other molecular markers indicate that Nmb is highly and selectively expressed in nociceptive and itch-sensitive DRG neurons.
The majority of dSC Grp is synthesized locally in dorsal spinal cord neurons. On the other hand, Nmb is highly expressed in pain- and itch-sensing DRG neurons. Our findings provide direct anatomic evidence that Grp could function locally in the dorsal spinal cord in addition to its roles in DRG neurons and that Nmb has potential roles in nociceptive and itch-sensitive neurons. These results will improve our understanding about roles of Grp and Nmb in mediating itch sensation.
痒觉是主要的躯体感觉模态之一。一些最新的研究结果表明，胃泌素释放肽（GRP）在背根神经节（DRG）神经元的亚群中表达，并作为一种选择性神经递质，将痒觉信息传递到脊髓中间神经元。然而，来自公共数据库和早期文献的表达数据表明，GRP mRNA 仅在背侧脊髓（dSC）中检测到，而其家族成员神经降压素 B（NMB）则在 DRG 神经元中高度表达。这些相互矛盾的结果表明，有必要对 GRP 和 NMB 的表达进行全面描述。
GRP mRNA 在幼年和成年小鼠的 dSC 中高度表达，但在 DRG 中几乎检测不到。抗脑肠肽血清特异性识别 GRP，但不识别 NMB。GRP 存在于少数小直径 DRG 神经元中，并在脊髓的 I 和 II 层中大量存在。背根切断后 dSC GRP 的减少与 DRG 衍生标志物的减少显著不同，但与脊髓神经元标志物的减少相似。NMB 和其他分子标志物的双荧光原位杂交表明，NMB 在痛觉和痒觉敏感的 DRG 神经元中高度且选择性表达。
大多数 dSC GRP 是由背侧脊髓神经元在局部合成的。另一方面，NMB 在痛觉和痒觉敏感的 DRG 神经元中高度表达。我们的研究结果提供了直接的解剖学证据，表明 GRP 除了在 DRG 神经元中的作用外，还可以在背侧脊髓中发挥局部作用，而 NMB 可能在痛觉和痒觉敏感神经元中发挥作用。这些结果将有助于我们理解 GRP 和 NMB 在介导痒觉中的作用。
