| First Author | Kiguchi N | Year | 2021 |
| Journal | Pharmacol Res Perspect | Volume | 9 |
| Issue | 3 | Pages | e00790 |
| PubMed ID | 34000759 | Mgi Jnum | J:353186 |
| Mgi Id | MGI:7666211 | Doi | 10.1002/prp2.790 |
| Citation | Kiguchi N, et al. (2021) Chemogenetic activation of central gastrin-releasing peptide-expressing neurons elicits itch-related scratching behavior in male and female mice. Pharmacol Res Perspect 9(3):e00790 |
| abstractText | Several lines of evidence have clarified that the key transmission pathways of itching sensation travel from the periphery to the central nervous system (CNS). Despite the functional significance of gastrin-releasing peptide (GRP) and its cognate receptor in the itch processing mechanism in the spinal dorsal horn (SDH), the roles of GRP-expressing (GRP(+) ) neurons in different regions remain unclear. This study aimed to determine whether GRP(+) neurons in the CNS directly modulated itch processing. To specifically activate spinal and supraspinal GRP neurons by the designer receptors exclusively activated by designer drugs (DREADDs) system, CAG-LSL-Gq-DREADD mice were crossed with GRP-Cre mice, resulting in the development of GRP-hM3Dq mice. Immunohistochemistry showed that hM3Dq was highly expressed in the SDH and brainstem closely related to sensory processing. The intraperitoneal, intrathecal, or intracerebroventricular administration of clozapine-N-oxide, an agonist of hM3Dq, strongly elicited dermatome-dependent itch-related scratching behavior, but did not change pain sensitivity. Importantly, GRP-Gq-DREADD-mediated scratching behavior in GRP-hM3Dq mice was not affected by the ablation of transient receptor potential vanilloid 1(+) sensory C-fibers, and it was also observed to a similar degree under chronic itch conditions. Furthermore, there were no significant sex differences in the scratching behavior elicited by GRP-Gq-DREADD, suggesting that itch-dominant roles of central GRP(+) neurons might be common in both sexes, at least under normal physiological conditions. These novel findings not only contribute to understanding the functional roles of central GRP(+) neurons further, but also propose the development of future effective therapeutics for intractable itching. |
