The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity.
The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity.
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DOI：
10.1016/j.pain.2014.03.012
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发表时间：
2014-07
期刊：
影响因子：
7.4
通讯作者：
Vulchanova L
中科院分区：
文献类型：
--
作者：
Fairbanks CA;Peterson CD;Speltz RH;Riedl MS;Kitto KF;Dykstra JA;Braun PD;Sadahiro M;Salton SR;Vulchanova L
VGF（非首字母缩写）是一种类颗粒蛋白，它在受调控的分泌途径中被包装并经蛋白水解加工。VGF及其加工产生的肽与学习、记忆、抑郁和慢性疼痛相关的神经可塑性有关。在感觉神经元中，外周神经损伤和炎症后VGF会迅速增加。从VGF的C末端产生的几种生物活性肽具有促伤害性的脊髓效应。本研究的目的是检验肽TLQP - 21的脊髓效应，并确定它是否参与持续性疼痛的脊髓机制。在外源性TLQP - 21应用后，在温水浸泡甩尾试验中诱导出剂量依赖性的热痛觉过敏。这种痛觉过敏被一种p38丝裂原活化蛋白激酶抑制剂以及环氧化酶和脂氧合酶抑制剂所抑制。我们利用对TLQP - 21的免疫中和来确定内源性肽在持续性疼痛潜在机制中的功能。在皮内注射完全弗氏佐剂的小鼠中，在炎症诱导前或诱导后5小时鞘内给予抗 - TLQP21免疫球蛋白G，可剂量依赖性地抑制触觉超敏和热痛觉过敏。在神经病理性疼痛的保留神经损伤模型中，鞘内给予抗 - TL21也减弱了触觉超敏的发展和维持。这些结果提供了证据，表明内源性TLQP - 21肽有助于炎症和神经损伤后脊髓神经可塑性的机制。
VGF (non-acronymic) is a granin-like protein that is packaged and proteolytically processed within the regulated secretory pathway. VGF and peptides derived from its processing have been implicated in neuroplasticity associated with learning, memory, depression, and chronic pain. In sensory neurons, VGF is rapidly increased following peripheral nerve injury and inflammation. Several bioactive peptides generated from the C-terminus of VGF have pro-nociceptive spinal effects. The goal of the present study was to examine the spinal effects of the peptide TLQP-21 and determine whether it participates in spinal mechanisms of persistent pain. Application of exogenous TLQP-21 induced dose-dependent thermal hyperalgesia in the warm water immersion tail withdrawal test. This hyperalgesia was inhibited by a p38 MAPK inhibitor as well as inhibitors of cyclooxygenase and lipoxygenase. We used immunoneutralization of TLQP-21 to determine the function of the endogenous peptide in mechanisms underlying persistent pain. In mice injected intradermally with complete Freund’s adjuvant, intrathecal treatment with anti-TLQP21 IgG immediately prior to or 5 h after induction of inflammation dose-dependently inhibited tactile hypersensitivity and thermal hyperalgesia. Intrathecal anti-TL21 administration also attenuated the development and maintenance of tactile hypersensitivity in the spared nerve injury model of neuropathic pain. These results provide evidence that endogenous TLQP-21 peptide contributes to the mechanisms of spinal neuroplasticity after inflammation and nerve injury.
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DOI：
10.1523/jneurosci.3145-08.2008
发表时间：
2008-09-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bozdagi O;Rich E;Tronel S;Sadahiro M;Patterson K;Shapiro ML;Alberini CM;Huntley GW;Salton SR
通讯作者：
Salton SR
影响因子：
1.7
作者：
Fitzsimmons BL;Zattoni M;Svensson CI;Steinauer J;Hua XY;Yaksh TL
通讯作者：
Yaksh TL
影响因子：
7.4
作者：
Fu ES;Zhang YP;Sagen J;Candiotti KA;Morton PD;Liebl DJ;Bethea JR;Brambilla R
通讯作者：
Brambilla R
DOI：
10.1074/jbc.m113.510917
发表时间：
2013-11-29
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chen YC;Pristerá A;Ayub M;Swanwick RS;Karu K;Hamada Y;Rice AS;Okuse K
通讯作者：
Okuse K
影响因子：
16.2
作者：
Hahm, S;Mizuno, TM;Salton, SRJ
通讯作者：
Salton, SRJ