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Molecular Pain

Xuhui Li, Takanori Matsuura, Ren-Hao Liu, Man Xue, Min Zhuo
The neuropeptide of calcitonin gene-related peptide (CGRP) plays critical roles in chronic pain, especially in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas including pain perception related prefrontal anterior cingulate cortex (ACC). However, less information is available for the functional roles of CGRP in cortical regions such as the ACC. Recent studies have consistently demonstrated that long-term potentiation (LTP) is a key cellular mechanism for chronic pain in the ACC...
February 5, 2019: Molecular Pain
Jian Zhang, Luping Wang, Hushan Wang, Zhenbo Su, Xiaochuan Pang
Pain is one of the most common and distressing symptoms suffered by patients with progression of cancer; however, the mechanisms responsible for hyperalgesia are not well understood. Since the midbrain periaqueductal gray (PAG) is an important component of the descending inhibitory pathway controlling on central pain transmission, in this study we examined the role for pro-inflammatory cytokines (PICs) of the PAG in regulating mechanical and thermal hyperalgesia evoked by bone cancer via PI3K-mTOR signals. Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats to induce mechanical and thermal hyperalgesia...
February 5, 2019: Molecular Pain
Huadong Ni, Long Sheng Xu, Yungong Wang, Hongbo Li, Kang An, Liu Mingjuan, Liu Qianying, Houshen Deng, He Qiuli, Huang Bing, Jian-Qiao Fang, Ming Yao
Descending nociceptive modulation from the supraspinal structures has an important role in cancer-induced bone pain (CIBP). Midbrain ventrolateral periaqueductal gray (vlPAG) is a critical component of descending nociceptive circuits; nevertheless, its precise cellular and molecular mechanisms involved in descending facilitation remain elusive. Our previous study has shown that activation of p38 MAPK in vlPAG microglia is essential for the neuropathic pain sensitization. However, the existence of potential connection between astrocytes and JNK pathway in CIBP has not yet been elucidated...
January 30, 2019: Molecular Pain
Yingwei Wu, Yingping Wang, Juan Wang, Qi Fan, Jinyu Zhu, Liu Yang, Weifang Rong
Elevated excitability of primary afferent neurons underlies chronic pain in patients with functional or inflammatory bowel diseases. Recent studies have established an essential role for an enhanced transient receptor potential vanilloid subtype 1 (TRPV1) signaling in mediating peripheral hyperalgesia in inflammatory conditions. Since co-localization of Toll-like receptor 4 (TLR4) and TRPV1 has been observed in primary afferents including the trigeminal sensory neurons and the dorsal root ganglion (DRG) neurons, we test the hypothesis that TLR4 might regulate the expression and function of TRPV1 in primary afferent neurons in TNBS-induced colitis using the TLR4-deficient and the wild type (WT) C57 mice...
January 23, 2019: Molecular Pain
Lan Zhang, Frank Stüber, Christoph Lippuner, Marcel Schiff, Ulrike M Stamer
Little is known about the mechanisms involved in the regulation of nociceptin and its receptor (NOP) in response to inflammation and pain in humans. In this study, specific signaling path-ways contributing to the regulation of nociceptin and NOP in human peripheral blood leuko-cytes were investigated. After approval by the ethics committee, peripheral blood obtained from healthy donors was cultured with or without phorbol-12-myristate-13-acetate (PMA). Prepronociceptin (ppNOC) and NOP mRNA were analyzed by real-time quantitative PCR, and nociceptin concentrations in culture supernatants by fluorescent enzyme immunoassay...
January 21, 2019: Molecular Pain
Ana Mm Oliveira, Christian Litke, Eszter Paldy, Anna M Hagenston, Jianning Lu, Rohini Kuner, Hilmar Bading, Daniela Mauceri
Chronic pain is a pathological manifestation of neuronal plasticity supported by altered gene transcription in spinal cord neurons that results in long-lasting hypersensitivity. Recently, the concept that epigenetic regulators might be important in pathological pain has emerged, but a clear understanding of the molecular players involved in the process is still lacking. In this study we linked Dnmt3a2, a synaptic activity-regulated de novo DNA methyltransferase, to chronic inflammatory pain. We observed that Dnmt3a2 levels are increased in the spinal cord of adult mice following plantar injection of Complete Freund's Adjuvant (CFA), an in vivo model of chronic inflammatory pain...
January 13, 2019: Molecular Pain
Chun-Lin Mai, Xiao Wei, Ya-Nan Xu, Jun Zhang, Zhen Jia Lin, Zhi Tan, Ying-Tong Meng, Yong-Yong Li, Li-Jun Zhou, Xian-Guo Liu
Accumulating evidence shows that inhibition of glycogen synthase kinase-3beta (GSK-3β) ameliorates cognitive impairments caused by a diverse array of diseases. Our previous work show that spared nerve injury (SNI) that induces neuropathic pain causes short-term memory (STM) deficits.Here,we reported that GSK-3β activity was enhanced in hippocampus and reduced in spinal dorsal horn following SNI, and the changes persisted for at least 45 d. Repetitive applications of selective GSK-3β inhibitors (SB216763, 5 mg/kg, i...
January 11, 2019: Molecular Pain
Camron D Bryant, Deniz Bagdas, Lisa R Goldberg, Tala Khalefa, Eric R Reed, Stacey L Kirkpatrick, Julia C Kelliiher, Melanie M Chen, William E Johnson, Megan K Mulligan, M Imad Damaj
Sensitivity to different pain modalities has a genetic basis that remains largely unknown. Employing closely related inbred mouse substrains can facilitate gene mapping of nociceptive behaviors in preclinical pain models. We previously reported enhanced sensitivity to acute thermal nociception in C57BL/6J (B6J) versus C57BL/6N (B6N) substrains. Here, we expanded on nociceptive phenotypes and observed an increase in formalin-induced inflammatory nociceptive behaviors and paw diameter in B6J versus B6N mice (Charles River Laboratories)...
January 11, 2019: Molecular Pain
Simona D'Agnelli, Lars Arendt-Nielsen, Maria Carla Gerra, Lorenzo Boggiani, Marco Baciarello, Elena Bignami
Fibromyalgia (FM) is a disease characterized by chronic widespread pain with additional symptoms, such as joint stiffness, fatigue, sleep disturbance, cognitive dysfunction, and depression. Currently FM diagnosis is based exclusively on a comprehensive clinical assessment, according to 2016 ACR criteria, but validated biological biomarkers associated with FM have not yet been identified. Genome-wide association studies investigated genes potentially involved in FM pathogenesis highlighting that genetic factors are possibly responsible for up to 50% of the disease susceptibility...
November 29, 2018: Molecular Pain
Nitin Agarwal, Johanna P Helmstaedter, Daniel Rangel Roja, Kiran Kumar Bali, Vijayan Gangadharan, Rohini Kuner
Diabetic peripheral neuropathy (DPN) is a major debilitating late complication of diabetes, which significantly reduces the quality of life in patients. DPN is associated with a wide spectrum of sensory abnormalities, where in loss of sensation or hypoalgesia to applied external stimuli is paradoxically accompanied by debilitating tonic spontaneous pain. In numerous studies on animal models of DPN, behavioural measurements have been largely confined to analysis of evoked withdrawal to mechanical and thermal stimuli applied to dermatomes, whereas spontaneous, on-going pain has not been widely studied...
November 20, 2018: Molecular Pain
Akihiro Yamada, Kohei Koga, Kazuhiko Kume, Masahiro Ohsawa, Hidemasa Furue
Recent studies have shown that ethanol produces a widespread modulation of neuronal activity in the CNS. It is not fully understood, however, how ethanol changes nociceptive transmission. We investigated acute effects of ethanol on synaptic transmission in the substantia gelatinosa (SG, lamina II of the spinal dorsal horn) and mechanical responses in the spinal dorsal horn. In SG neurons, bath-application of ethanol at low concentration (10 mM) did not change the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs)...
November 19, 2018: Molecular Pain
Kimberly Stephens, Zhiyong Chen, Eellan Sivanesan, Srinivasa Raja, Bengt Linderoth, Sean D Tavernn, Yun Guan
Spinal cord stimulation (SCS) has become an important modality in pain treatment especially for neuropathic pain conditions refractory to pharmacotherapy. However, the molecular control of inhibitory and excitatory mechanisms observed after SCS are poorly understood. Here we used RNA-seq to identify differences in the expression of genes and gene networks in spinal cord tissue from nerve-injured rats with and without repetitive conventional SCS treatment. Five weeks after chronic constrictive injury (CCI) to the left sciatic nerve, male and female rats were randomized to receive repetitive SCS or no treatment...
November 19, 2018: Molecular Pain
Wenxin Zhang, Dan Drzymalski, Lihong Sun, Qi Xu, CuiCui Jiao, Luyang Wang, Shufang Xie, Xiaowei Qian, Hui Wu, Fei Xiao, Feng Fu, Ying Feng, Xinzhong Chen
Metabotropic glutamate receptor 5 (mGluR5) and transient receptor potential vanilloid subtype 1 (TRPV1) have been shown to play critical roles in the transduction and modulation of cutaneous nociception in the central nervous system. However, little is known regarding the possible involvement of mGluR5 and TRPV1 in regulating visceral nociception from the uterine cervix. In this study, we used a rat model of uterine cervical distension (UCD) to examine the effects of noxious stimuli to the uterine cervix on expression of spinal mGluR5 and TRPV1...
November 16, 2018: Molecular Pain
Yong Fei Fan, Shao Yu Guan, Li Luo, Yan Jiao Li, Le Yang, Xuan Xuan Zhou, Guo Dong Guo, Ming-Gao Zhao, Qi Yang, Gang Liu
Tetrahydroxystilbene Glucoside (THSG) is one of the active ingredients of Polygonum multiflorum. It has been shown to exert a variety of pharmacological effects, including antioxidant, anti-aging, anti-atherosclerosis. Because of its prominent anti-inflammatory effect, we explored whether THSG had analgesic effect. In this study, we used a model of chronic inflammatory pain caused by injection of complete Freund's adjuvant (CFA) into the hind paw of mice. We found THSG, relieved swelling and pain in the hind paw of mice on a dose-dependent manner...
November 1, 2018: Molecular Pain
Albert Leung, Eric Yang, Michael Lim, Valerie Metzger-Smith, Rebecca Theilmann, David Song, Lisa Lin, Alice Tsai, Roland Lee
The occurrence of debilitating chronic persistent (24/7) headache after mild traumatic brain injury (MTBI) represents a central neuropathic pain state. Previous studies suggest that this chronic headache (HA) state can be attributed to altered supraspinal modulatory functional connectivity in both resting and evoked pain states. Abnormalities in the myelin sheaths along the supraspinal Superior Longitudinal Fasciculus (SLF) and Anterior Thalamic Radiation (ATR) are frequently associated with alteration in pain modulation related to functional connectivity deficit with the prefrontal cortex...
October 16, 2018: Molecular Pain
Mei Yang, Wenyun Xu, Yiru Wang, Xin Jiang, Yingke Li, Yajuan Yang, Hong Bin Yuan
Neuroinflammation plays an important role in the induction and maintenance of chronic pain. Orchestra of pattern-recognition receptors (PRRs) induced pro-inflammatory and anti-inflammatory cytokines are critical for inflammation homeostasis. CD11b on macrophages could inhibit toll like receptor (TLR) activation induced inflammatory responses. However, the function of CD11b on microglia remains unknown. In the current study, we demonstrated that CD11b deficient microglia cells produced more inflammatory cytokines such as IL-6 and TNF-α, while less anti-inflammatory cytokines...
October 3, 2018: Molecular Pain
Qi-Yu Chen, Tao Chen, Li-Jun Zhou, Xian-Guo Liu, Min Zhuo
Spinal nociceptive transmission receives biphasic modulation from supraspinal structures. Recent studies demonstrate that the anterior cingulate cortex (ACC) facilitates spinal excitatory synaptic transmission and nociceptive reflex. However, whether the top-down descending facilitation can cause long-term synaptic changes in spinal cord remains unclear. In the present study, we recorded C-fiber evoked field potentials in spinal dorsal horn and found that the ACC stimulation caused enhancement of C fiber mediated responses...
August 14, 2018: Molecular Pain
Kord M Kober, Adam Olshen, Yvettte P Conley, Mark Schumacher, Kimberly Topp, Betty Smoot, Melissa Mazor, Margaret Chesney, Marilyn Hammer, Steven M Paul, Jon D Levine, Christine Miaskowski
BACKGROUND: Paclitaxel is one of the most commonly used drugs to treat breast cancer. Its major dose-limiting toxicity is paclitaxel-induced peripheral neuropathy (PIPN). PIPN persists into survivorship and has a negative impact on patient's mood, functional status, and quality of life. No interventions are available to treat PIPN. A critical barrier to the development of efficacious interventions is the lack of understanding of the mechanisms that underlie PIPN. Mitochondrial dysfunction has been evaluated in preclinical studies as a hypothesized mechanism for PIPN, but clinical data to support this hypothesis are limited...
January 2018: Molecular Pain
Veronica I Shubayev, Alex Y Strongin, Tony L Yaksh
Complex regional pain syndrome is an extremely painful condition that develops after trauma to a limb. Complex regional pain syndrome exhibits autoimmune features in part mediated by autoantibodies against muscarinic-2 acetylcholine (M2) receptor. The mechanisms underlying the M2 receptor involvement in complex regional pain syndrome remain obscure. Based on our recent work demonstrating that limb nerve trauma releases a potent proalgesic, immunodominant myelin basic protein fragment, our present sequence database analyses reveal an unexpected and previously undescribed structural homology of the proalgesic myelin basic protein fragment with the M2 receptor...
January 2018: Molecular Pain
Talia Adi, Mark Estacion, Betsy R Schulman, Steven Vernino, Sulayman D Dib-Hajj, Stephen G Waxman
Voltage-gated sodium channel Nav 1.7 is a threshold channel in peripheral dorsal root ganglion (DRG), trigeminal ganglion, and sympathetic ganglion neurons. Gain-of-function mutations in Nav 1.7 have been shown to increase excitability in DRG neurons and have been linked to rare Mendelian and more common pain disorders. Discovery of Nav 1.7 variants in patients with pain disorders may expand the spectrum of painful peripheral neuropathies associated with a well-defined molecular target, thereby providing a basis for more targeted approaches for treatment...
January 2018: Molecular Pain
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