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Source: Pain
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Total 14 results found since Jan 2013.
Oral squamous cell carcinoma–released brain-derived neurotrophic factor contributes to oral cancer pain by peripheral tropomyosin receptor kinase B activation
Oral cancer pain is debilitating and understanding mechanisms for it is critical to develop novel treatment strategies treatment strategies. Brain-derived neurotrophic factor (BDNF) signaling is elevated in oral tumor biopsies and is involved with tumor progression. Whether BDNF signaling in oral tumors contributes to cancer-induced pain is not known. The current study evaluates a novel peripheral role of BDNF-tropomyosin receptor kinase B (TrkB) signaling in oral cancer pain. Using human oral squamous cell carcinoma (OSCC) cells and an orthotopic mouse tongue cancer pain model, we found that BDNF levels were upregulated i...
Source: Pain - February 14, 2022 Category: Anesthesiology Tags: Research Paper Source Type: research
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
NLRP2 inflammasome in dorsal root ganglion as a novel molecular platform that produces inflammatory pain hypersensitivity
This study investigated the existence of the inflammasome in dorsal root ganglion (DRG) and the functional significance in the development of inflammatory pain hypersensitivity. Tissue inflammation was induced in male C57BL/6 mice with complete Freund's adjuvant (CFA) or ceramide injection into the hind paw. Behavioral testing was performed to investigate inflammation-induced pain hypersensitivity. Ipsilateral L5 DRGs were obtained for analysis. Expression of nucleotide oligomerization domain-like receptors (NLRs) was analyzed with real-time PCR. Cleaved interleukin (IL)-1β and NLRP2 expression was investigated with immun...
Source: Pain - August 21, 2019 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
Chronic stress-associated visceral hyperalgesia correlates with severity of intestinal barrier dysfunction
In humans, chronic psychological stress is associated with increased intestinal paracellular permeability and visceral hyperalgesia, which is recapitulated in the chronic intermittent water avoidance stress (WAS) rat model. However, it is unknown whether enhanced visceral pain and permeability are intrinsically linked and correlate. Treatment of rats with lubiprostone during WAS significantly reduced WAS-induced changes in intestinal epithelial paracellular permeability and visceral hyperalgesia in a subpopulation of rats. Lubiprostone also prevented WAS-induced decreases in the epithelial tight junction protein, occludin ...
Source: Pain - August 23, 2018 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
Epac–protein kinase C alpha signaling in purinergic P2X3R-mediated hyperalgesia after inflammation
Abstract: Sensitization of purinergic P2X3 receptors (P2X3Rs) is a major mechanism contributing to injury-induced exaggerated pain responses. We showed in a previous study that cyclic adenosine monophosphate (cAMP)–dependent guanine nucleotide exchange factor 1 (Epac1) in rat sensory dorsal root ganglia (DRGs) is upregulated after inflammatory injury, and it plays a critical role in P2X3R sensitization by activating protein kinase C epsilon (PKCε) inside the cells. protein kinase C epsilon has been established as the major PKC isoform mediating injury-induced hyperalgesic responses. On the other hand, the role of PKCα ...
Source: Pain - July 1, 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
Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia
Summary: Knocking down expression of the sodium channel isoform NaV1.6 in lumbar sensory ganglia blocked development of pain behaviors and neuronal hyperexcitability induced by local inflammation of the ganglion.Abstract: Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models and initiates many other pat...
Source: Pain - March 7, 2013 Category: Anesthesiology Authors: Wenrui Xie, Judith A. Strong, Ling Ye, Ju-Xian Mao, Jun-Ming Zhang Tags: Research papers Source Type: research
