Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons

详细信息    查看全文

• 作者：B.K. Taylor ; W. Fu ; K.E. Kuphal ; C.-O. Stiller ; M.K. Winter ; W. Chen ; G.F. Corder ; J.H. Urban ; K.E. McCarson ; J.C. Marvizon
• 关键词：aCSF ; artificial cerebrospinal fluid ; ANOVA ; analysis of variance ; CGRP ; calcitonin gene-related peptide ; CFA ; complete Freund&rsquo ; s adjuvant ; DRG ; dorsal root ganglion ; HEPES ; 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid ; IB4 ; isolectin-B4 ; NK1R ; neurokinin 1 receptor ; NPY ; neuropeptide Y ; PBS ; phosphate-buffered saline ; RIA ; radioimmunoassay ; SP ; substance P ; SP-LI ; SP-like immunoreactivity
• 刊名：Neuroscience
• 出版年：3 January, 2014
• 年：2014
• 卷：256
• 期：Complete
• 页码：178-194
• 全文大小：2616 K

文摘

Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in the dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in the microdialysate of the dorsal horn. NPY also decreased non-noxious stimulus (paw brush)-evoked NK1R internalization (as well as mechanical hyperalgesia and mechanical and cold allodynia) after intraplantar injection of carrageenan. Similarly, in rat spinal cord slices with dorsal root attached, [Leu³¹, Pro³⁴]-NPY inhibited dorsal root stimulus-evoked NK1R internalization. In rat dorsal root ganglion neurons, Y1 receptors colocalized extensively with calcitonin gene-related peptide (CGRP). In dorsal horn neurons, Y1 receptors were extensively expressed and this may have masked the detection of terminal co-localization with CGRP or SP. To determine whether the pain inhibitory actions of Y1 receptors are enhanced by inflammation, we administered [Leu³¹, Pro³⁴]-NPY after intraplantar injection of complete Freund鈥檚 adjuvant (CFA) in rat. We found that [Leu³¹, Pro³⁴]-NPY reduced paw clamp-induced NK1R internalization in CFA rats but not uninjured controls. To determine the contribution of increased Y1 receptor-G protein coupling, we measured [³⁵S]GTP纬S binding simulated by [Leu³¹, Pro³⁴]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating the inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception.