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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
Kord Kober, Adam Olshen, Yvette P Conley, Mark A Schumacher, Kimberly Topp, Betty Smoot, Melissa Mazor, Margaret Chesney, Marilyn Hammer, Steven Paul, Jon 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 (MD) has been evaluated in pre-clinical studies as a hypothesized mechanism for PIPN, but clinical data to support this hypothesis is limited...
November 14, 2018: Molecular Pain
Veronica Shubayev, Alex Strongin, Tony Yaksh
Complex regional pain syndrome (CRPS) is an extremely painful condition that develops after trauma to a limb. CRPS exhibits autoimmune features in part mediated by autoantibodies against muscarinic-2 acetylcholine (M2) receptor. The mechanisms underlying the M2 receptor involvement in CRPS remain obscure. Based on our recent work demonstrating that limb nerve trauma releases a potent proalgesic, immunodominant myelin basic protein (MBP) fragment, our present sequence database analyses reveal an unexpected and previously undescribed structural homology of the proalgesic MBP fragment with the M2 receptor...
November 5, 2018: Molecular Pain
Talia Adi, Mark Estacion, Betsy R Schulman, Steven Vernino, Sulayman Dib-Hajj, Stephen Waxman
Voltage-gated sodium channel Nav1.7 is a threshold channel in peripheral dorsal root ganglion (DRG), trigeminal ganglion, and sympathetic ganglion neurons. Gain-of-function mutations in Nav1.7 have been shown to increase excitability in DRG neurons and have been linked to rare Mendelian and more common pain disorders. Discovery of Nav1.7 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...
November 5, 2018: Molecular Pain
Irina Schaefer, Vincenzo Prato, Alice Arcourt, Francisco J Taberner, Stefan G Lechner
Nerve growth factor (NGF) is an inflammatory mediator that induces long-lasting hyperalgesia, which can partially be attributed to NGF-induced sensitization of primary afferent nociceptors. It was shown that NGF increases the excitability of polymodal C-fiber nociceptors by modulating TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) voltage-gated sodium channels, but hitherto only little is known about the effects of NGF on sodium currents in other nociceptor subtypes that express the NGF receptor TrkA. We previously characterized two reporter mouse lines that allow the unequivocal identification of two important subclasses of TrkA-expressing nociceptors - i...
November 2, 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
Viacheslav Viatchenko-Karpinski, Jianguo Gu
Cooling temperatures and low pH have profound effects on somatosensory functions including nociception. The effects not only can be mediated by cooling temperature transducers and proton transducers expressed in subpopulations of somatosensory neurons, but may also be mediated by ion channels involving membrane excitability such as voltage-dependent K+ channels in somatosensory neurons. In the present study, we performed the in situ patch-clamp recordings from nociceptive-like trigeminal ganglion (TG) neurons in ex vivo TG preparations of adult rats...
October 31, 2018: Molecular Pain
Min Jee Kim, Motomasa Tanioka, Sun Woo Um, Seong-Karp Hong, Bae Hwan Lee
The insular cortex (IC) is an important brain region involved in the processing of pain and emotion. Recent studies indicate that lesions in the IC induce pain asymbolia and reverse neuropathic pain. Endogenous cannabinoids (endocannabinoids, eCBs), which have been shown to attenuate pain, are simultaneously degraded by fatty acid amide hydrolase (FAAH) that halts the mechanisms of action. Selective inhibitor URB597 suppresses FAAH activity by conserving eCBs, which reduces pain. The present study examined the analgesic effects of URB597 treatment in the IC of an animal model of neuropathic pain...
October 31, 2018: Molecular Pain
Hyunjung Min, Woo-Hyun Cho, Hyunkyoung Lee, Boomin Choi, Han Kyu Lee, Yoon-Jung Kim, Yeonhee Joo, Sung Jun Jung, Se-Young Choi, Soojin Lee, Sung Joong Lee
We have previously reported that histamine-induced pruritus was attenuated in TLR4 knockout (KO) mice due to decreased TRPV1 sensitivity. Our results implied that TLR4 potentiated TRPV1 activation in sensory neurons; however, the molecular mechanism has yet to be elucidated. In this study, we investigated the molecular mechanisms of TLR4-mediated TRPV1 potentiation using TLR4-deficient sensory neurons and a heterologous expression system. Primary sensory neurons were obtained from WT or TLR4 KO mice, and HEK293T cells expressing TRPV1 and TLR4 were prepared by transient transfection...
October 25, 2018: Molecular Pain
Florian Niedermirtl, Mirjam Eberhardt, Barbara Namer, Andreas Leffler, Carla Nau, Peter W Reeh, Katrin Kistner
Etomidate is a preferred drug for induction of general anesthesia in cardiovascular risk patients. As with propofol and other perioperatively used anesthetics the application of aqueous etomidate formulations causes an intensive burning pain upon injection. Such algogenic properties of etomidate have been attributed to the solubilizer propylene glycol (PG) which represents 35 % of the solution administered clinically. The aim of this study was to investigate the underlying molecular mechanisms which lead to injection pain of aqueous etomidate formulations...
October 22, 2018: Molecular Pain
Ge Yang, Lunhao Chen, Zhihua Gao, Yue Wang
Back pain is common and costly. Although lumbar disc degeneration has long been regarded as a major contributor to back pain, how disc degeneration leads to back pain remains unclear. Recent studies observed microglia activation in the spinal cord after disc degeneration, suggesting activated microglia may be involved in discogenic back pain. To determine whether microglia activation participates in disc degeneration-induced back pain, we used a modified disc puncture-induced degeneration-related back pain mouse model to examine the changes of spinal microglia and investigate the potential link between microglia activation and discogenic back pain...
October 17, 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
Jing Li
The medial prefrontal cortex (mPFC) is a key area for the regulation of pain and emotion. However, the functional involvement of the mPFC for visceral nociception, at the neuronal or synaptic level, is obscure yet. In the present study, the properties of excitatory and inhibitory synaptic transmission within the layer II/III of rat mPFC after chronic myocardial infarction (CMI) were studied. It's found that the excitation-inhibition ratio (E/I ratio) of the mPFC was greatly changed, with enhanced excitation and decreased inhibition inputs to the pyramidal cells of the mPFC, which largely due to decreased spike firing in GABAergic neurons...
October 10, 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
Elín I Magnúsdóttir, Mirjana Grujic, Axel Roers, Karin Hartmann, Gunnar Pejler, Malin C Lagerström
Subcutaneous formalin injections are used as a model for tissue injury-induced pain where formalin induces pain and inflammation indirectly by crosslinking proteins, and directly through activation of the transient receptor potential A1 receptor on primary afferents. Activation of primary afferents leads to both central and peripheral release of neurotransmitters. Mast cells are found in close proximity to peripheral sensory nerve endings and express receptors for neurotransmitters released by the primary afferents, contributing to the neuro/immune interface...
October 3, 2018: Molecular Pain
Ieva Satkeviciute, Andrew Dilley
Many patients with neuropathic pain present without signs of nerve injury on routine clinical examination. Some of these patients may have inflamed peripheral nerves (neuritis). In this study, we have examined whether neuritis causes changes within the dorsal horn that may contribute to a central pain mechanism. Comparisons have been made to a model of axonal transport disruption induced using vinblastine, since neuritis disrupts such processes. At the peak of cutaneous hypersensitivities, recordings from wide dynamic range (WDR) neurons revealed increases in wind-up following neuritis but not vinblastine treatment...
August 21, 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
Yong Fang Zhu, Jacek M Kwiecien, Wojciech Dabrowski, Robert Ungard, Kan Lun Zhu, Jan D Huizinga, James L Henry, Gurmit Singh
Evidence suggests that there are both nociceptive and neuropathic components of cancer-induced pain. We have observed that changes in intrinsic membrane properties and excitability of normally non-nociceptive Aβ sensory neurons are consistent in rat models of peripheral neuropathic pain and cancer-induced pain. This has prompted a comparative investigation of the intracellular electrophysiological characteristics of sensory neurons and of the ultrastructural morphology of the dorsal horn in rat models of neuropathic pain and cancer-induced pain...
January 2018: Molecular Pain
Samiha S Shaikh, Michael S Nahorski, C Geoffrey Woods
Bi-allelic dysfunctional mutations in nerve growth factor (NGF) cause the rare human phenotype hereditary sensory and autonomic neuropathy type 5 (HSAN5). We describe a novel NGF mutation in an individual with typical HSAN5 findings. The mutation c.361C>T, p.R121W is at the last residue of the furin cleavage motif Arg-Ser-Lys-Arg in proNGF. We show that the p.R121W mutation completely abolishes the formation of mature NGF-β. Surprisingly, mutant p.R121W cells produced very little proNGF. Instead, the two progressive cleavage products of proNGF were produced, proA-NGF and proB-NGF, with proB-NGF being the predominant NGF-derived peptide and the only peptide secreted by mutant p...
January 2018: Molecular Pain
Anna Rita Zuena, Daniela Maftei, Giovanni Sebastiano Alemà, Francesca Dal Moro, Roberta Lattanzi, Paola Casolini, Ferdinando Nicoletti
Vortioxetine is a multimodal antidepressant that potently antagonizes 5-HT3 serotonin receptors, inhibits the high-affinity serotonin transporter, activates 5-HT1A and 5-HT1B receptors, and antagonizes 5-HT1D and 5-HT7 receptors. 5-HT3 receptors largely mediate the hyperalgesic activity of serotonin that occurs in response to nerve injury. Activation of 5-HT3 receptors contributes to explain why selective serotonin reuptake inhibitors, such as fluoxetine, are not indicated in the treatment of neuropathic pain...
January 2018: Molecular Pain
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