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Sympathectomy decreases pain behaviors and nerve regeneration by downregulating monocyte chemokine CCL2 in dorsal root ganglia in the rat tibial nerve crush model
In this study, we examined the effect of a localized “microsympathectomy,” ie, cutting the gray rami containing sympathetic postganglionic axons where they enter the L4 and L5 spinal nerves, which is more analogous to clinically used sympathetic blockade compared with chemical or surgical sympathectomy. We also examined manipulations of CCL2 (monocyte chemoattractant protein 1), a key player in both regeneration and pain. We used rat tibial nerve crush as a neuropathic pain model in which peripheral nerve regeneration can occur successfully. CCL2 in the sensory ganglia was increased by tibial nerve crush and reduced by...
Source: Pain - December 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury
In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. Chronic constriction injury produced a time-dependent increase in the level of OCT1 protein in the ipsilateral L4/5 DRG, but not in the spinal cord. Blocking this increase through microinjection of OCT1 siRNA into the ipsilateral L4/5 DRG attenuated the initiation and maintenance of CCI-induced mechanical allodynia, heat hyperalgesia, and cold allodynia and improved morphine analgesia after CCI, without affecting basal respons...
Source: Pain - January 24, 2019 Category: Anesthesiology Tags: Research Paper Source Type: research

Epigenetic upregulation of CXCL12 expression mediates antitubulin chemotherapeutics–induced neuropathic pain
Abstract: Clinically, Microtubule-targeted agents–induced neuropathic pain hampers chemotherapeutics for patients with cancer. Here, we found that application of paclitaxel or vincristine increased the protein and mRNA expression of CXCL12 and frequency and amplitude of miniature excitatory post synaptic currents (mEPSCs) in spinal dorsal horn neurons. Spinal local application of CXCL12 induced the long-term potentiation of nociceptive synaptic transmission and increased the amplitude of mEPSCs. Inhibition of CXCL12 using the transgenic mice (CXCL12−/+) or neutralizing antibody or siRNA ameliorated the mEPSC's enhancem...
Source: Pain - March 25, 2017 Category: Anesthesiology Tags: Research Paper Source Type: research

CaMKIIα underlies spontaneous and evoked pain behaviors in Berkeley sickle cell transgenic mice
This study aimed to investigate the functional involvement of Ca2+/calmodulin-dependent protein kinase II (CaMKIIα) in the persistent and refractory pain associated with SCD. We found that nonevoked ongoing pain as well as evoked hypersensitivity to mechanical and thermal stimuli were present in Berkeley sickle cell transgenic mice (BERK mice), but not nonsickle control littermates. Prominent activation of CaMKIIα was observed in the dorsal root ganglia and spinal cord dorsal horn region of BERK mice. Intrathecal administration of KN93, a selective inhibitor of CaMKII, significantly attenuated mechanical allodynia and he...
Source: Pain - November 22, 2016 Category: Anesthesiology Tags: Research Paper Source Type: research

TRAF6 upregulation in spinal astrocytes maintains neuropathic pain by integrating TNF-α and IL-1β signaling
In this study, we investigated the role of TRAF6 in neuropathic pain in mice after spinal nerve ligation (SNL). SNL induced persistent TRAF6 upregulation in the spinal cord. Interestingly, TRAF6 was mainly colocalized with the astrocytic marker glial fibrillary acidic protein on SNL day 10 and partially expressed in microglia on SNL day 3. In cultured astrocytes, TRAF6 was upregulated after exposure to TNF-α or IL-1β. TNF-α or IL-1β also increased CCL2 expression, which was suppressed by both siRNA and shRNA targeting TRAF6. TRAF6 siRNA treatment also inhibited the phosphorylation of c-Jun N-terminal kinase (JNK) in as...
Source: Pain - September 29, 2014 Category: Anesthesiology Authors: Ying Lu, Bao-Chun Jiang, De-Li Cao, Zhi-Jun Zhang, Xin Zhang, Ru-Rong Ji, Yong-Jing Gao Tags: Research papers Source Type: research

MrgC agonism at central terminals of primary sensory neurons inhibits neuropathic pain
Summary: Our research suggests that MrgC agonism at spinal sites constitutes a novel pain inhibitory mechanism in rodent models of neuropathic pain.Abstract: Chronic neuropathic pain is often refractory to current pharmacotherapies. The rodent Mas-related G-protein-coupled receptor subtype C (MrgC) shares substantial homogeneity with its human homologue, MrgX1, and is located specifically in small-diameter dorsal root ganglion neurons. However, evidence regarding the role of MrgC in chronic pain conditions has been disparate and inconsistent. Accordingly, the therapeutic value of MrgX1 as a target for pain treatment in hum...
Source: Pain - December 12, 2013 Category: Anesthesiology Authors: Shao-Qiu He, Zhe Li, Yu-Xia Chu, Liang Han, Qian Xu, Man Li, Fei Yang, Qin Liu, Zongxiang Tang, Yun Wang, Niyada Hin, Takashi Tsukamoto, Barbara Slusher, Vinod Tiwari, Ronen Shechter, Feng Wei, Srinivasa N. Raja, Xinzhong Dong, Yun Guan Tags: Research papers Source Type: research

Unexpected association of the “inhibitory” neuroligin 2 with excitatory PSD95 in neuropathic pain
Summary: Modified expression and function of the adhesion molecule neuroligin 2 are involved in the excitation/inhibition imbalance leading to the dorsal horn network’s hyperexcitability in neuropathic rats.Abstract: In the spinal nerve ligation (SNL) model of neuropathic pain, synaptic plasticity shifts the excitation/inhibition balance toward excitation in the spinal dorsal horn. We investigated the deregulation of the synaptogenic neuroligin (NL) molecules, whose NL1 and NL2 isoforms are primarily encountered at excitatory and inhibitory synapses, respectively. In the dorsal horn of SNL rats, NL2 was overexpressed whe...
Source: Pain - July 29, 2013 Category: Anesthesiology Authors: Tiphaine Dolique, Alexandre Favereaux, Olivier Roca-Lapirot, Virginie Roques, Claire Léger, Marc Landry, Frédéric Nagy Tags: Research papers Source Type: research

Gelsemine, a principal alkaloid from Gelsemium sempervirens Ait., exhibits potent and specific antinociception in chronic pain by acting at spinal α3 glycine receptors
TOC summary: Gelsemine produces potent and specific antinociception in chronic pain states by activating spinal α3 glycine receptors without inducing tolerance.Abstract: The present study examined the antinociceptive effects of gelsemine, the principal alkaloid in Gelsemium sempervirens Ait. A single intrathecal injection of gelsemine produced potent and specific antinociception in formalin-induced tonic pain, bone cancer-induced mechanical allodynia, and spinal nerve ligation-induced painful neuropathy. The antinociception was dose-dependent, with maximal inhibition of 50% to 60% and ED50 values of 0.5 to 0.6μg. Multipl...
Source: Pain - July 24, 2013 Category: Anesthesiology Authors: Jing-Yang Zhang, Nian Gong, Jin-Lu Huang, Ling-Chen Guo, Yong-Xiang Wang Tags: Research papers Source Type: research

Full-length membrane-bound tumor necrosis factor-α acts through tumor necrosis factor receptor 2 to modify phenotype of sensory neurons
Summary: Membrane-bound tumor necrosis factor-α, acting through tumor necrosis factor receptor 2, causes increased expression in dorsal root ganglia of genes whose products are implicated in heightened neuronal excitability characteristic of chronic neuropathic pain.Abstract: Neuropathic pain resulting from spinal hemisection or selective spinal nerve ligation is characterized by an increase in membrane-bound tumor necrosis factor-alpha (mTNFα) in spinal microglia without detectable release of soluble TNFα (sTNFα). In tissue culture, we showed that a full-length transmembrane cleavage-resistant TNFα (CRTNFα) construc...
Source: Pain - May 28, 2013 Category: Anesthesiology Authors: Zetang Wu, Shiyong Wang, Sandy Gruber, Marina Mata, David J. Fink Tags: Research papers Source Type: research