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dorsal horn neurons

Tanziyah Muqeem, Biswarup Ghosh, Vitor Pinto, Angelo C Lepore, Manuel Covarrubias
Presynaptic voltage-gated K+ (Kv) channels in dorsal root ganglion (DRG) neurons are thought to regulate nociceptive synaptic transmission in the spinal dorsal horn. However, the Kv channel subtypes responsible for this critical role have not been identified. The Kv3.4 channel is particularly important because it is robustly expressed in DRG nociceptors, where it regulates action potential (AP) duration. Furthermore, Kv3.4 dysfunction is implicated in the pathophysiology of neuropathic pain in multiple pain models...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Nynke J van den Hoogen, Jacob Patijn, Dick Tibboel, Bert A Joosten, Maria Fitzgerald, Charlie Ht Kwok
Noxious stimulation at critical stages of development has long-term consequences on somatosensory processing in later life, but it is not known whether this developmental plasticity is restricted to nociceptive pathways. Here we investigate the effect of repeated neonatal noxious or innocuous hind-paw stimulation upon adult spinal dorsal horn cutaneous mechanical sensitivity. Neonatal Sprague-Dawley rats of both sexes received four unilateral left hind-paw needle pricks (NP, n=13) or four tactile (cotton swab touch) stimuli, per day (TC, n=11) for the first 7 days of life...
March 8, 2018: Pain
Ji-Yuan Zhao, Li Yang, Hu-Hu Bai, Jiang-Ping Liu, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
Protein tyrosine phosphatase 1B (PTP1B) has been shown to dephosphorylate and inactivate insulin receptors, which contributes to the pathogenesis of diabetes. Neuropathic pain is one of the severe complications that results from diabetic neuropathy. However, whether PTP1B was involved in the development of diabetic neuropathic pain is largely unknown. The current study illustrated that PTP1B was located in spinal cord dorsal horn neurons of Sprague-Dawley rats. Western blot analysis demonstrated that the diabetic neuropathic pain induced by intraperitoneal injection of streptozotocin was associated with an increased protein expression and a dynamic redistribution of spinal PTP1B into excitatory glutamatergic synapses...
March 8, 2018: European Journal of Pharmacology
Daeyeong Chung, Dae-Chul Cho, Seong-Hyun Park, Kyoung-Tae Kim, Joo-Kyung Sung, Younghoon Jeon
OBJECTIVE: The purpose of this study was to evaluate pain-related behaviors after bilateral C2 root resection and change in pain patterns in the suboccipital region in rats. METHODS: Male Sprague-Dawley rats were randomly assigned to three groups (n=25/group); näive, sham, and C2 resection. Three, 7, 10, and 14 days after surgery, cold allodynia was assessed using 20 μL of 99.7% acetone. c-Fos and c-Jun were immunohistochemically stained to evaluate activation of dorsal horn gray matter in C2 segments of the spinal cord 2 hours, 1 day, 7 days, and 14 days after surgery...
March 2018: Journal of Korean Neurosurgical Society
Melissa Anne Tadros, Brett Anthony Graham, Robert John Callister
In this issue of the Journal of Physiology, Balachandar and Prescott (2018) model the action potential discharge patterns (ie, spiking types) that have long been used to classify superficial dorsal horn (SDH: lamina I-II) neurons by varying the expression levels of two potassium conductances. This article is protected by copyright. All rights reserved.
March 10, 2018: Journal of Physiology
Sascha R A Alles, Peter A Smith
Injury to or disease of the nervous system can invoke chronic and sometimes intractable neuropathic pain. Many parallel, interdependent, and time-dependent processes, including neuroimmune interactions at the peripheral, supraspinal, and spinal levels, contribute to the etiology of this "disease of pain." Recent work emphasizes the roles of colony-stimulating factor 1, ATP, and brain-derived neurotrophic factor. Excitatory processes are enhanced, and inhibitory processes are attenuated in the spinal dorsal horn and throughout the somatosensory system...
April 2018: Pharmacological Reviews
Silvia M S Sandes, Luana Heimfarth, Renan G Brito, Priscila L Santos, Daniele N Gouveia, Alexandra M S Carvalho, Jullyana S S Quintans, Edeildo F da Silva-Júnior, Thiago M de Aquino, Paulo H B França, João X de Araújo-Júnior, Ricardo L C Albuquerque-Júnior, Gokhan Zengin, Martine Schmitt, Jean-Jacques Bourguignon, Lucindo J Quintans-Júnior
BACKGROUND: Indole-3-guanylhydrazone hydrochloride (LQM01) is a new derivative of aminoguanidine hydrochloride, an aromatic aminoguanidine. METHODS: Mice were treated with LQM01 (5, 10, 25 or 50 mg/kg, i.p.), vehicle (0.9% saline i.p.) or a standard drug. The mice were subjected to carrageenan-induced pleurisy, abdominal writhing induced by acetic acid, the formalin test and the hot-plate test. The model of non-inflammatory chronic muscle pain induced by saline acid was also used...
February 27, 2018: Chemico-biological Interactions
Maria Gutierrez-Mecinas, Erika Polgár, Andrew M Bell, Marine Herau, Andrew J Todd
The superficial dorsal horn (laminae I and II) of the spinal cord contains numerous excitatory and inhibitory interneurons, and recent studies have shown that each of these groups can be divided into several neurochemically distinct populations. Although it has long been known that some neurons in this region have intersegmental (propriospinal) axonal projections, there have been conflicting reports concerning the number of propriospinal cells and the extent of their axons. In addition, little is known about the neurochemical phenotype of propriospinal neurons or about the termination pattern of their axons...
March 1, 2018: Brain Structure & Function
Jinjun Chen, Lingyong Li, Shao-Rui Chen, Hong Chen, Jing-Dun Xie, Rita E Sirrieh, David M MacLean, Yuhao Zhang, Meng-Hua Zhou, Vasanthi Jayaraman, Hui-Lin Pan
α2δ-1, commonly known as a voltage-activated Ca2+ channel subunit, is a binding site of gabapentinoids used to treat neuropathic pain and epilepsy. However, it is unclear how α2δ-1 contributes to neuropathic pain and gabapentinoid actions. Here, we show that Cacna2d1 overexpression potentiates presynaptic and postsynaptic NMDAR activity of spinal dorsal horn neurons to cause pain hypersensitivity. Conversely, Cacna2d1 knockdown or ablation normalizes synaptic NMDAR activity increased by nerve injury. α2δ-1 forms a heteromeric complex with NMDARs in rodent and human spinal cords...
February 27, 2018: Cell Reports
Jennifer J DeBerry, Vijay K Samineni, Bryan A Copits, Christopher J Sullivan, Sherri K Vogt, Kathryn M Albers, Brian M Davis, Robert W Gereau Iv
Bladder-innervating primary sensory neurons mediate reflex-driven bladder function under normal conditions, and contribute to debilitating bladder pain and/or overactivity in pathological states. The goal of this study was to examine the respective roles of defined subtypes of afferent neurons in bladder sensation and function in vivo via direct optogenetic activation. To accomplish this goal, we generated transgenic lines that express a Channelrhodopsin-2-eYFP fusion protein (ChR2-eYFP) in two distinct populations of sensory neurons: TRPV1-lineage neurons ( Trpv1 Cre ;Ai32, the majority of nociceptors) and Nav 1...
2018: Frontiers in Integrative Neuroscience
Shu-Hung Huang, Sheng-Hua Wu, Su-Shin Lee, Yun-Nan Lin, Chee-Yin Chai, Chung-Sheng Lai, Hui-Min David Wang
Objective: No effective treatments have yet been developed for burn-induced neuropathic pain. Platelet-rich plasma (PRP) has been reported to ameliorate various types of inflammation pain. However, the effect of PRP on burn-induced neuropathic pain is unclear. Methods: Burn-induced neuropathic pain Sprague-Dawley rat model was confirmed using a mechanical response test 4 weeks after the burn injuries were sustained, following which PRP was injected in the scar area. The rats were divided into four groups (n = 6) as following: Group A, Sham; Group B, Sham + PRP; Group C, Burn; and Group D, Burn + PRP...
2018: International Journal of Medical Sciences
Rafael Salas, Karla Ramirez, Victor Tortorici, Horacio Vanegas, Enrique Vazquez
The so-called on- and off-cells of the rostral ventromedial medulla (RVM) send their axons to the spinal dorsal horn. Activation of on-cells precedes and coincides with a facilitation, and activation of off-cells coincides with an inhibition, of withdrawal reflexes elicited by noxious agents. Considerable evidence supports the notion that on- and off-cells modulate nocifensive reflexes during opioid and non-opioid action and also during normal circumstances and during peripheral neuropathy and inflammation...
February 21, 2018: Brain Research
Kornél Király, Márk Kozsurek, Erika Lukácsi, Benjamin Barta, Alán Alpár, Tamás Balázsa, Csaba Fekete, Judit Szabon, Zsuzsanna Helyes, Kata Bölcskei, Valéria Tékus, Zsuzsanna E Tóth, Károly Pap, Gábor Gerber, Zita Puskár
Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states...
February 22, 2018: Scientific Reports
Ryoichi Tashima, Keisuke Koga, Misuzu Sekine, Kensho Kanehisa, Yuta Kohro, Keiko Tominaga, Katsuyuki Matsushita, Hidetoshi Tozaki-Saitoh, Yugo Fukazawa, Kazuhide Inoue, Hiromu Yawo, Hidemasa Furue, Makoto Tsuda
Neuropathic pain is caused by peripheral nerve injury (PNI). One hallmark symptom is allodynia (pain caused by normally innocuous stimuli), but its mechanistic underpinning remains elusive. Notably, whether selective stimulation of non-nociceptive primary afferent Aβ fibers indeed evokes neuropathic pain-like sensory and emotional behaviors after PNI is unknown, because of the lack of tools to manipulate Aβ fiber function in awake, freely moving animals. In this study, we used a transgenic rat line that enables stimulation of non-nociceptive Aβ fibers by a light-activated channel (channelrhodopsin-2; ChR2)...
January 2018: ENeuro
Jamie K Moy, Arkady Khoutorsky, Marina N Asiedu, Gregory Dussor, Theodore J Price
Plasticity in dorsal root ganglion (DRG) neurons that promotes pain requires activity-dependent mRNA translation. Protein synthesis inhibitors block the ability of many pain-promoting molecules to enhance excitability in DRG neurons and attenuate behavioral signs of pain plasticity. In line with this, we have recently shown that phosphorylation of the 5' cap-binding protein, eIF4E, plays a pivotal role in plasticity of DRG nociceptors in models of hyperalgesic priming. However, mRNA targets of eIF4E phosphorylation have not been elucidated in the DRG...
2018: Frontiers in Cellular Neuroscience
Fang-Xiong Zhang, Vinicius M Gadotti, Ivana A Souza, Lina Chen, Gerald W Zamponi
Cavα2δ subunits contribute to the cell-surface expression of Cav2 calcium channels. Upregulation of Cavα2δ-1 in dorsal root ganglion neurons occurs after nerve injury and results in an increased synaptic abundance of Cav2.2 channels in the spinal dorsal horn, thus enhancing the transmission of pain signals. Here, we report that large conductance calcium-activated potassium (BK) channels interact with the Cavα2δ subunit. Coexpression of BK channels with the Cav2 calcium channels reduces their cell-surface expression and whole-cell current density by competing the Cavα2δ subunit away from the Cav2 complex...
February 20, 2018: Cell Reports
Keiya Takahashi, Hyun Yi, Ching-Hang Liu, Shue Liu, Yuta Kashiwagi, Dennis J Patin, Shuanglin Hao
The symptoms of HIV-sensory neuropathy are dominated by neuropathic pain. Recent data show that repeated use of opiates enhances the chronic pain states in HIV patients. Limited attention has so far been devoted to exploring the exact pathogenesis of HIV painful disorder and opiate abuse in vivo, for which there is no effective treatment. Bromodomain-containing protein 4 (Brd4) is a member of the bromodomain and extraterminal domain protein (BET) family and functions as a chromatin 'reader' that binds acetylated lysines in histones in brain neurons to mediate the transcriptional regulation underlying learning and memory...
February 20, 2018: Neuroreport
Shiwei Wang, Diya Su, Jing Li, Dezhi Li, Hong Wan, Michael Schumacher, Song Liu
OBJECTIVE In this study, the authors used a surgical model of end-to-side neurorrhaphy between a nerve graft and a donor tibial nerve in adult rats to investigate the optimal conditions for axonal regeneration induced by the donor nerve. They also assessed the importance of a more favorable pathway using a predegenerated nerve graft to attract regenerating axons to regrow into the graft and then directing and improving their growth toward the target in comparison with results obtained with a fresh nerve graft...
February 16, 2018: Journal of Neurosurgery
E Contreras-Hernández, D Chávez, E Hernández, E Velázquez, P Reyes, J Bejar, M Martín, U Cortés, S Glusman, P Rudomin
Despite the profuse information on the molecular and cellular mechanisms involved in the central sensitization produced by intense nociceptive stimulation, the changes in the patterns of functional connectivity between spinal neurones associated with the development of secondary hyperalgesia and allodynia remain largely unknown. Here we show that the state of central sensitization produced by the intradermal injection of capsaicin is associated with structured transformations in neuronal synchronization that lead to an enduring reorganization of the functional connectivity within a segmentally distributed ensemble of dorsal horn neurones...
February 16, 2018: Journal of Physiology
Pan Gu, Zhiqiang Pan, Xiao-Min Wang, Liting Sun, Lydia Wai Tai, Chi Wai Cheung
A strong link between histone deacetylases (HDACs) and nociceptive hypersensitivity has been indicated in different pain models. However, the underlying molecular and cellular mechanisms remain elusive. Here, we discovered that partial sciatic nerve ligation-induced mechanical allodynia and thermal hyperalgesia in mice were associated with increased mRNA and protein expressions of HDAC5 (a member of class IIa HDACs) and SRY-related HMG-box 10 (SOX10) in the ipsilateral lumbar dorsal horn. Gene knockdown of spinal HDAC5 or SOX10 attenuated partial sciatic nerve ligation-induced nociceptive hypersensitivity, companied with decrease of spinal neuronal sensitization markers, namely phosphorylated-Erk, phosphorylated-GluN1 (ser896), and c-Fos...
March 2018: Pain
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