Potential antipruritic neuronal targets of nalfurafine in murine spinal dorsal horn
Potential antipruritic neuronal targets of nalfurafine in murine spinal dorsal horn
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纳芙拉芬在小鼠脊髓背角的潜在止痒神经元靶标
DOI：
10.1097/itx.0000000000000066
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Takamori K
中科院分区：
文献类型：
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作者：
Honda K;Tominaga M;Kusube F;Takamori K
Materials and Methods:To reveal the antipruritic action of nalfurafine in the murine spinal dorsal horn, we conducted in vivo electrophysiology, behavioral experiments, and high-sensitive in situ hybridization (ISH) using normal C57BL/6J mice.Results:Behavioral analyses indicated that intrathecal injection of nalfurafine reduced, but not entirely eliminated the gastrin-releasing peptide (GRP)-evoked scratching bouts. In vivo electrophysiological recordings revealed that nalfurafine administration suppressed chloroquine (CQ)-responsive dorsal horn neurons in 15.8%(3/19) of mice. In fact, only 1 of 3 nalfurafine-suppressed mice responded to GRP. ISH in 3 sections of the spinal cord showed that 24.8%(154/623) were double-positive for GRP and KOR and 13.6%(68/431) for GRP receptor (GRPR) and KOR in total KOR+ cells. Most KOR+ cells were negative for GRP and GRPR. Intrathecal injection of dynorphin-saporin did not change the number of scratching bouts caused by GRP. However, it reduced the number of scratching bouts evoked by intradermal injection of CQ.Discussion:In conclusion, our data suggest that nalfurafine targets both GRP+ KOR+ and GRPR+ KOR+ cells which are present in a 2: 1 ratio and suppresses CQ-induced itch in the spinal dorsal horn. These findings suggest that GRP+ KOR-or GRPR+ KOR-cells may function as interneurons in the spinal neuronal pathway of itch.
