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dorsal horn neurons

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https://www.readbyqxmd.com/read/29781959/involvement-of-the-vgf-derived-peptide-tlqp-62-in-nerve-injury-induced-hypersensitivity-and-spinal-neuroplasticity
#1
Alexander G J Skorput, Xijing Zhang, Jonathan J Waataja, Cristina D Peterson, Maureen S Riedl, Kelley F Kitto, Hai Truong, Cecilia Huffman, Stephen R Salton, Carolyn A Fairbanks, Christopher N Honda, Lucy Vulchanova
Neuroplasticity in the dorsal horn following peripheral nerve damage contributes critically to the establishment of chronic pain. The neurosecretory protein VGF (non-acronymic) is rapidly and robustly upregulated following nerve injury, and therefore peptides generated from it are positioned to serve as signals for peripheral damage. The goal of this project was to understand the spinal modulatory effects of the C-terminal VGF derived peptide TLQP-62 at the cellular level and gain insight into the function of the peptide in the development of neuropathic pain...
May 16, 2018: Pain
https://www.readbyqxmd.com/read/29780163/heteromerization-of-%C3%AE-opioid-receptor-and-cholecystokinin-b-receptor-through-the-third-transmembrane-domain-of-the-%C3%AE-opioid-receptor-contributes-to-the-anti-opioid-effects-of-cholecystokinin-octapeptide
#2
Yin Yang, Qian Li, Qi-Hua He, Ji-Sheng Han, Li Su, You Wan
Activation of the cholecystokinin type B receptor (CCKBR) by cholecystokinin octapeptide (CCK-8) inhibits opioid analgesia. Chronic opiate treatment leads to an increase in the CCK-8 concentration and thus enhances the antagonism of CCK-8 against opioid analgesia; the underlying molecular mechanisms remain of great interest. In the present study, we validated the colocalization of the μ-opioid receptor (MOR) and CCKBR in pain signal transmission-related spinal cord dorsal horn and dorsal root ganglion neurons of rats...
May 21, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29774960/alteration-of-nociceptive-integration-in-the-spinal-cord-of-a-rat-model-of-parkinson-s-disease
#3
Keri-Ann Charles, Frédéric Naudet, Rabia Bouali-Benazzouz, Marc Landry, Philippe De Deurwaerdère, Pascal Fossat, Abdelhamid Benazzouz
BACKGROUND: Pain is a major non motor symptom that contributes to impaired quality of life in PD. However, its mechanism is unknown. OBJECTIVES AND METHODS: We sought to identify the pain phenotypes and parallel changes in spinal integration of peripheral stimuli in a rat model of PD induced by lesions of SN dopamine neurons, using behavioral plantar and von Frey tests as well as electrophysiology of the dorsal horn. RESULTS: We show that dopamine depletion by 6-OHDA induced hypersensitivity to mechanical and thermal stimuli...
May 18, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29772390/pathobiology-of-christianson-syndrome-linking-disrupted-endosomal-lysosomal-function-with-intellectual-disability-and-sensory-impairments
#4
Mallory Kerner-Rossi, Maria Gulinello, Steven Walkley, Kostantin Dobrenis
Christianson syndrome (CS) is a recently described rare neurogenetic disorder presenting early in life with a broad range of neurological symptoms, including severe intellectual disability with nonverbal status, hyperactivity, epilepsy, and progressive ataxia due to cerebellar atrophy. CS is due to loss-of-function mutations in SLC9A6, encoding NHE6, a sodium-hydrogen exchanger involved in the regulation of early endosomal pH. Here we review what is currently known about the neuropathogenesis of CS, based on insights from experimental models, which to date have focused on mechanisms that affect the CNS, specifically the brain...
May 14, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29758384/disruption-of-shp1-nmda-receptor-signaling-in-spinal-cord-dorsal-horn-alleviated-inflammatory-pain
#5
Li Yang, Hu-Hu Bai, Zi-Yang Zhang, Jiang-Ping Liu, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
Src-homology 2 domain-containing protein tyrosine phosphatase-1 (SHP1) is one of the non-receptor-like phosphatases that are highly enriched in hematopoietic cells. Although accumulating evidence has implicated the protein tyrosine phosphatases in the regulation of nociceptive transmission and plasticity, it is largely unknown whether SHP1 was expressed in pain-related spinal cord dorsal horn and engaged in the synaptic modification of nociceptive signals. Here we found that SHP1 was present in spinal neurons of rats and functionally coupled to GluN2A subunit-containing N-methyl-d-aspartate subtype of glutamate receptors, one of the key players in central sensitization of nociceptive behaviors...
April 30, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29752984/antinociceptive-effects-of-the-antidepressant-phenelzine-are-mediated-by-context-dependent-inhibition-of-neuronal-responses-in-the-dorsal-horn
#6
Liam E Potter, Suzanne Doolen, Katherine Mifflin, Gustavo Tenorio, Glen Baker, Bradley K Taylor, Bradley J Kerr
The putative strong anti-nociceptive properties of the antidepressant phenelzine (PLZ) have not been widely explored as a treatment for pain. Antinociceptive effects of PLZ were identified in the formalin model of tonic pain (Mifflin et al. 2016) and in allodynia associated with experimental autoimmune encephalomyelitis, (EAE) a mouse model of multiple sclerosis (Potter et al. 2016). Here, we further clarify the specific types of stimuli and contexts in which PLZ modulates nociceptive sensitivity. Our findings indicate that PLZ selectively inhibits ongoing inflammatory pain while sparing transient reflexive and acute nociception...
May 9, 2018: Neuroscience
https://www.readbyqxmd.com/read/29752983/orexin-b-modulates-spontaneous-excitatory-and-inhibitory-transmission-in-lamina-ii-neurons-of-adult-rat-spinal-cord
#7
Chong Wang, Tsugumi Fujita, Eiichi Kumamoto
Cellular mechanisms underlying the antinociceptive properties of orexins, a group of neuropeptides produced by the hypothalamus, in the spinal dorsal horn have not been thoroughly investigated. We examined how orexin B affects spontaneous synaptic transmission in lamina II neurons, which play a pivotal role in regulating nociceptive transmission, by applying a whole-cell patch-clamp technique to lamina II neurons in adult rat spinal cord slices. In 66% of neurons tested, bath-applied orexin B concentration-dependently produced an inward current at -70 mV and/or increased the frequency of glutamatergic spontaneous excitatory postsynaptic current (sEPSC) without changing its amplitude, in a manner resistant to the voltage-gated Na+ -channel blocker tetrodotoxin...
May 9, 2018: Neuroscience
https://www.readbyqxmd.com/read/29746991/electrical-synapses-are-involved-in-orofacial-neuropathic-pain
#8
Omar Ouachikh, Aziz Hafidi, Yves Boucher, Wisam Dieb
Accumulated evidences suggest important roles of glial GAP-junctions in pain. However, only a few studies have explored the role of neuronal GAP-junctions or electrical synapses in neuropathic pain (NP). Therefore, the present study explores the role of connexin 36 (Cx36) in NP using the chronic constriction injury of the infraorbital nerve (CCI-IoN) model in rat. A significant increase in Cx36 labeling was observed in the medullary dorsal horn (MDH) of CCI-IoN-lesioned compared to sham rats. The expression of Cx36 in CCI-IoN-lesioned rats revealed a rostroventral gradient of punctuate labeling within lamina IIo of the MDH...
May 7, 2018: Neuroscience
https://www.readbyqxmd.com/read/29733975/role-of-trpv1-and-trpv4-in-surgical-incision-induced-tissue-swelling-and-fos-like-immunoreactivity-in-the-central-nervous-system-of-mice
#9
Yasuhito Motojima, Haruki Nishimura, Hiromichi Ueno, Satomi Sonoda, Kazuaki Nishimura, Kentaro Tanaka, Reiko Saito, Mitsuhiro Yoshimura, Takashi Maruyama, Takanori Matsuura, Hitoshi Suzuki, Makoto Kawasaki, Hideo Ohnishi, Akinori Sakai, Yoichi Ueta
Pain management remains a major concern regarding the treatment of postoperative patients. Transient receptor potential (TRP) channels are considered to be new therapeutic targets for pain control. We investigated whether the genes Trpv1 and Trpv4 are involved in hind paw swelling caused after surgical incision in mice or in incision-induced Fos-like immunoreactivity (Fos-LI) levels in the central nervous system. Mice were divided into four groups: wild-type (WT) control, WT incision, Trpv1 knockout (Trpv1-/- ) incision, and Trpv4 knockout (Trpv4-/- ) incision...
May 4, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29729250/application-of-optogenetics-in-the-study-of-pain-modulation
#10
REVIEW
Yu-Feng Xie, Jing Wang, Robert P Bonin
Intractable pain is the single most common cause of disability, affecting more than 20% of the population world-wide. There is accordingly a global effort to decipher how changes in the activity of nociceptive sensory afferents and dorsal horn cell populations contribute to the onset and maintenance of chronic pain. Through the application of advances in genetic techniques, there has been a surge in the success of efforts along this front. In particular, the past several years have brought rapid progress in the adaptation of optogenetic approaches to study and manipulate the activity of sensory afferents and spinal cord neurons in freely behaving animals...
May 2, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29723522/transcriptomic-profiling-of-trigeminal-nucleus-caudalis-and-spinal-cord-dorsal-horn
#11
Lisette J A Kogelman, Rikke Elgaard-Christensen, Jes Olesen, Inger Jansen-Olesen, Thomas F Hansen
The pain sensation system is highly conserved among species, thus animal models have been used to investigate relevant tissues. The focus for head-specific pain has been on the primary nociceptive neurons in the trigeminal pathway, i.e. trigeminal ganglia. The secondary nociceptive neurons of the trigeminal pathway, trigeminal nucleus caudalis (TNC), have not been assessed. We expect different gene expression profiles compared to the homologous spinal cord dorsal horn (SDH), as several signalling substances provoke head-specific pain but not peripheral pain...
April 30, 2018: Brain Research
https://www.readbyqxmd.com/read/29722912/region-specific-deletions-of-the-glutamate-transporter-glt1-differentially-affect-nerve-injury-induced-neuropathic-pain-in-mice
#12
Zhuoyang Zhao, Yuichi Hiraoka, Hiroshi Ogawa, Kohichi Tanaka
Glutamate is a major excitatory neurotransmitter and plays an important role in neuropathic pain, which is frequently caused by nerve damage. According to recent studies, nerve injury induces changes in glutamatergic transmission in the spinal cord and several supraspinal regions, including the periaqueductal gray (PAG). Among glutamate signaling components, accumulating evidence suggests that the glial glutamate transporter GLT1 plays a critical role in neuropathic pain. Indeed, GLT1 expression is reduced in the spinal cord but increased in the PAG after nerve injury, suggesting that the role of GLT1 in neuropathic pain may vary according to the brain region...
May 3, 2018: Glia
https://www.readbyqxmd.com/read/29717160/transcriptional-profiling-of-somatostatin-interneurons-in-the-spinal-dorsal-horn
#13
Alexander Chamessian, Michael Young, Yawar Qadri, Temugin Berta, Ru-Rong Ji, Thomas Van de Ven
The spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different somatosensory modalities. Somatostatin (SST)-expressing interneurons in the SDH have been implicated specifically in mediating mechanical pain. Identifying the transcriptomic profile of SST neurons could elucidate the unique genetic features of this population and enable selective analgesic targeting. To that end, we combined the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) method and Fluorescence Activated Nuclei Sorting (FANS) to capture tagged SST nuclei in the SDH of adult male mice...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29706124/sensorimotor-activity-partially-ameliorates-pain-and-reduces-nociceptive-fiber-density-in-the-chronically-injured-spinal-cord
#14
Christopher Sliwinski, Timo A Nees, Radhika Puttagunta, Norbert Weidner, Armin Blesch
A large proportion of patients suffering from spinal cord injury (SCI) develop chronic central neuropathic pain. Previously, we and others have shown that sensorimotor training early after SCI can prevent the development of mechanical allodynia. To determine whether training initiated in the subchronic/chronic phase remains effective, correlates of below level neuropathic pain were analyzed in the hindpaws 5-10 weeks after a moderate T11 contusion SCI (50 kDyn) in adult female C57BL/6 mice. Comparing SCI and sham mice 5 weeks post-injury, about 80% of injured animals developed mechanical hypersensitivity to light mechanical stimuli, whereas testing of noxious stimuli revealed hypo-responsiveness...
April 28, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29702090/the-endogenous-agonist-%C3%AE-alanine-activates-glycine-receptors-in-rat-spinal-dorsal-neurons
#15
Yutaka Seino, Nobuko Ohashi, Tatsuro Kohno
β-alanine is a structural analog of glycine and γ-aminobutyric acid (GABA) and is thought to be involved in the modulation of nociceptive information at the spinal cord. However, it is not known whether β-alanine exerts its effect in substantia gelatinosa (SG) neurons of the spinal dorsal horn, where glycine and GABA play an important role in regulating nociceptive transmission from the periphery. Here, we investigated the effects of β-alanine on inhibitory synaptic transmission in adult rat SG neurons using whole-cell patch-clamp...
April 24, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29697531/mice-lacking-kcns1-in-peripheral-neurons-show-increased-basal-and-neuropathic-pain-sensitivity
#16
Christoforos Tsantoulas, Franziska Denk, Massimo Signore, Mohammed A Nassar, Kensuke Futai, Stephen B McMahon
Voltage-gated potassium (Kv) channels are increasingly recognised as key regulators of nociceptive excitability. Kcns1 is one of the first potassium channels to be associated with neuronal hyperexcitability and mechanical sensitivity in the rat, as well as pain intensity and risk of developing chronic pain in humans. Here, we show that in mice Kcns1 is predominantly expressed in the cell body and axons of myelinated sensory neurons positive for neurofilament-200, including Aδ-fiber nociceptors and low-threshold Aβ mechanoreceptors...
April 24, 2018: Pain
https://www.readbyqxmd.com/read/29693281/recombinant-interleukin-4-alleviates-mechanical-allodynia-via-injury-induced-interleukin-4-receptor-alpha-in-spinal-microglia-in-a-rat-model-of-neuropathic-pain
#17
Hiroai Okutani, Hiroki Yamanaka, Kimiko Kobayashi, Masamichi Okubo, Koichi Noguchi
Glial cells play important roles in the development and maintenance of neuropathic pain. In particular, activated microglia in the spinal cord facilitate the hyper-excitability of dorsal horn neurons after peripheral nerve injury via pro-inflammatory molecules. In this study, we investigated the possible involvement of the anti-inflammatory cytokine, interleukin-4 (IL-4), in neuropathic pain. We did not detect the expression of IL-4 mRNA in the rat dorsal root ganglion or spinal cord; however, peripheral nerve injury induced the expression of IL-4 receptor (IL-4R) alpha mRNA in the spinal cord...
April 25, 2018: Glia
https://www.readbyqxmd.com/read/29686262/neuronal-atlas-of-the-dorsal-horn-defines-its-architecture-and-links-sensory-input-to-transcriptional-cell-types
#18
Martin Häring, Amit Zeisel, Hannah Hochgerner, Puneet Rinwa, Jon E T Jakobsson, Peter Lönnerberg, Gioele La Manno, Nilesh Sharma, Lotta Borgius, Ole Kiehn, Malin C Lagerström, Sten Linnarsson, Patrik Ernfors
The dorsal horn of the spinal cord is critical to processing distinct modalities of noxious and innocuous sensation, but little is known of the neuronal subtypes involved, hampering efforts to deduce principles governing somatic sensation. Here we used single-cell RNA sequencing to classify sensory neurons in the mouse dorsal horn. We identified 15 inhibitory and 15 excitatory molecular subtypes of neurons, equaling the complexity in cerebral cortex. Validating our classification scheme in vivo and matching cell types to anatomy of the dorsal horn by spatial transcriptomics reveals laminar enrichment for each of the cell types...
April 23, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29653184/estrogen-alleviates-neuropathic-pain-induced-after-spinal-cord-injury-by-inhibiting-microglia-and-astrocyte-activation
#19
Jee Youn Lee, Hae Young Choi, Bong Gun Ju, Tae Young Yune
Neuropathic pain after spinal cord injury (SCI) is developed in about 80% of SCI patients and there is no efficient therapeutic drug to alleviate SCI-induced neuropathic pain. Here we examined the effect of estrogen on SCI-induced neuropathic pain at below-level and its effect on neuroinflammation as underlying mechanisms. Neuropathic pain is developed at late phase after SCI and a single dose of 17β-estradiol (100, 300 μg/kg) were administered to rats with neuropathic pain after SCI through intravenous injection...
April 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29628771/activation-of-spinal-dorsal-horn-p2y-13-receptors-can-promote-the-expression-of-il-1%C3%AE-and-il-6-in-rats-with-diabetic-neuropathic-pain
#20
Rui Zhou, Tao Xu, XiaoHong Liu, YuanShou Chen, DeYing Kong, Hong Tian, Mingxia Yue, Dujuan Huang, Junwei Zeng
Objective: The dorsal horn P2Y13 receptor is involved in the development of pain behavior induced by peripheral nerve injury. It is unclear whether the expression of proinflammatory cytokines interleukin (IL)-1β and IL-6 at the spinal dorsal horn are influenced after the activation of P2Y13 receptor in rats with diabetic neuropathic pain (DNP). Methods: A rat model of type 1 DNP was induced by intraperitoneal injection of streptozotocin (STZ). We examined the expression of P2Y13 receptor, Iba-1, IL-1β, IL-6, JAK2, STAT3, pTyr1336 , and pTyr1472 NR2B in rat spinal dorsal horn...
2018: Journal of Pain Research
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