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Takashi Suto, Daiki Kato, Hideaki Obata, Shigeru Saito
A rat model of neuropathic pain at 6 weeks after spinal nerve ligation (SNL6w) exhibits both mechanical hypersensitivity and impaired noxious stimuli-induced analgesia (NSIA). Repeated treatment with antidepressants can produce anti-hypersensitivity and restore NSIA. To examine the involvement of a brain-derived neurotrophic factor-mediated mechanism, a tropomyosin receptor kinase B (TrkB) agonist, 7,8-dihydroxyflavone (DHF), was administered to SNL6w rats (5 mg• kg-1 • day-1 , 5 days). Mechanical hypersensitivity was evaluated using the von Frey filament test and paw pressure test...
December 7, 2018: Journal of Pain: Official Journal of the American Pain Society
Mohammad-Reza Zarrindast, Fatemeh Khakpai
Nicotine, as the main component of tobacco, plays a key role in various behaviors of both humans and animals including reward, addiction, learning and memory, anxiety, pain as well as body weight and temperature. Nicotine exerts its function by activating nicotinic acetylcholine receptors (nAChRs) which one highly expressed throughout the nervous system. The mesocorticolimbic dopamine system mediates the processing of reward, learning and memory behaviors produced by nicotine. In addition, some structures of the central nervous system, such as the hippocampus and amygdala, have a major role in mediation of nicotine properties...
December 4, 2018: Brain Research
H Kramar, H Stepaniuk, N Voloshchuk, I Taran, S Kovalenko
An in-depth study of the pharmacological properties of 4-[4-oxo-(4h)-quinazolin-3-yl]-benzoic acid as an analgesic agent established that it had a sufficiently high analgesic effect on models of somatic and neuropathic pain syndromes. Study objective was to study the mechanisms of analgesic action of PK-66 compound in rats using the pharmacological analysis. We evaluated the mechanisms of analgesic effect of PK-66 (1 mg/kg, intraperitoneal) compound on the thermal irritation model on Hours 1, 2, 4 and 6 after administration of study compounds...
October 2018: Georgian Medical News
Su Chen, Yi Rong, Mengxue Liu, Song Cheng, Xiangming Liu, Xiaohong Li, Yi Yu, Guangzhong Yang, Xiaofei Yang
Triterpenoid saponins from Stauntonia chinensis (TSS) are potential therapeutic agents because of its analgesic properties. However, the underlying mechanisms of the anti-nociceptive activity of TSS are largely unclear, especially in CNS. The present study confirmed the analgesic effect of TSS using four models of acute pain based on thermal or chemical stimuli. TSS treatment specifically impaired the threshold of thermal- and chemical-stimulated acute pain. Naloxone did not block the anti-nociceptive effects of TSS, which showed no participation of the opioid system...
2018: Frontiers in Pharmacology
Petra Hundehege, Juncal Fernandez-Orth, Pia Römer, Tobias Ruck, Thomas Müntefering, Susann Eichler, Manuela Cerina, Lisa Epping, Sarah Albrecht, Amélie F Menke, Katharina Birkner, Kerstin Göbel, Thomas Budde, Frauke Zipp, Heinz Wiendl, Ali Gorji, Stefan Bittner, Sven G Meuth
BACKGROUND/AIMS: Multiple sclerosis (MS) is a prototypical autoimmune central nervous system (CNS) disease. Particularly progressive forms of MS (PMS) show significant neuroaxonal damage as consequence of demyelination and neuronal hyperexcitation. Immuno-modulatory treatment strategies are beneficial in relapsing MS (RMS), but mostly fail in PMS. Pregabalin (Lyrica®) is prescribed to MS patients to treat neuropathic pain. Mechanistically, it targets voltage-dependent Ca2+ channels and reduces harmful neuronal hyperexcitation in mouse epilepsy models...
November 27, 2018: Neuro-Signals
Phillip Kramer, Mahesh Rao, Crystal Stinson, Larry L Bellinger, Paul R Kinchington, Michael B Yee
Herpes zoster or shingles is the result of varicella zoster virus (VZV) infection and often results in chronic pain that lasts for months after visible symptoms subside. Testosterone often attenuates pain in males. Previous work demonstrates ovarian estrogen effects γ-aminobutyric acid (GABA) signaling in the thalamus, reducing pain but the role of testosterone within the thalamus is currently unknown. Because aromatase affects pain and is present in the thalamus we tested a hypothesis that testosterone converted to estrogen in the thalamus attenuates herpes zoster induced pain...
2018: Frontiers in Integrative Neuroscience
Mariacristina Mazzitelli, Enza Palazzo, Sabatino Maione, Volker Neugebauer
Glutamate is the main excitatory neurotransmitter in the nervous system and plays a critical role in nociceptive processing and pain modulation. G-protein coupled metabotropic glutamate receptors (mGluRs) are widely expressed in the central and peripheral nervous system, and they mediate neuronal excitability and synaptic transmission. Eight different mGluR subtypes have been identified so far, and are classified into Groups I-III. Group II mGluR2 and mGluR3 couple negatively to adenylyl cyclase through Gi/Go proteins, are mainly expressed presynaptically, and typically inhibit the release of neurotransmitters, including glutamate and GABA...
2018: Frontiers in Molecular Neuroscience
Yuhua Yin, Min-Hee Yi, Dong Woon Kim
Neuropathic pain (NP) is caused by lesions of the peripheral fibers and central neurons in the somatosensory nervous system and affects 7-10% of the general population. Although the distinct cause of neuropathic pain has been investigated in primary afferent neurons over the years, pain modulation by central sensitization remains controversial. NP is believed to be driven by cell type-specific spinal synaptic plasticity in the dorsal horn. Upon intense afferent stimulation, spinothalamic tract neurons are potentiated, whereas GABAergic interneurons are inhibited leading to long-term depression...
2018: Pain Research & Management: the Journal of the Canadian Pain Society
Yi-Hung Chen, Hsin-Jung Lee, Ming Tatt Lee, Ya-Ting Wu, Yen-Hsien Lee, Ling-Ling Hwang, Ming-Shiu Hung, Andreas Zimmer, Ken Mackie, Lih-Chu Chiou
Adequate pain management remains an unmet medical need. We previously revealed an opioid-independent analgesic mechanism mediated by orexin 1 receptor (OX1R)-initiated 2-arachidonoylglycerol (2-AG) signaling in the ventrolateral periaqueductal gray (vlPAG). Here, we found that low-frequency median nerve stimulation (MNS) through acupuncture needles at the PC6 (Neiguan) acupoint (MNS-PC6) induced an antinociceptive effect that engaged this mechanism. In mice, MNS-PC6 reduced acute thermal nociceptive responses and neuropathy-induced mechanical allodynia, increased the number of c-Fos-immunoreactive hypothalamic orexin neurons, and led to higher orexin A and lower GABA levels in the vlPAG...
November 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Yanlin Wang-Fischer, Tina Garyantes
The Streptozotocin- (STZ-) induced diabetic model is widely used; however, unexplained acute toxicity has given the model an unreliable reputation. To improve the reliability and utility of this model, we characterize the age dependence of STZ toxicity and introduce novel endpoints to assess diabetic complications and reveal possible mechanisms for diabetic development. Diabetes was induced by STZ injection into male, 6 to 23 weeks old, Sprague-Dawley rats. Their metabolic (glucose, lipids, and hormones), inflammatory (cytokines), histologic and behavioral endpoints were observed for 1...
2018: Journal of Diabetes Research
Ken-Ichiro Hayashida, James C Eisenach
Gabapentinoids are effective in a wide range of animal pain models and in patients with neuropathic pain and has become one of first-line treatments for neuropathic pain. Because spinal plasticity and sensitization have been intensely studied in neuropathic pain, most laboratory studies have focused on actions of gabapentinoids in the spinal cord, where they reduce primary afferent traffic and excitation of spinal nociceptive neurons, via interaction with α2δ subunits of voltage-gated Ca2+ channels. However, a recent clinical study questioned the relevance of this in vitro and in vivo rodent studies by demonstrating a complete lack of clinical efficacy of intrathecal gabapentin in patients with chronic pain...
2018: Advances in Experimental Medicine and Biology
Yaeko Yokoshima, Masahiko Sumitani, Daisuke Nishizawa, Makoto Nagashima, Kazutaka Ikeda, Ryoji Kato, Jun Hozumi, Hiroaki Abe, Kenji Azuma, Rikuhei Tsuchida, Yoshitsugu Yamada
AIM: Cancer pain impairs not only physical functions but also social functions and roles. Consequently, the overall health-related quality of life of patients with cancer pain deteriorates. Opioid analgesics are recommended for treating moderate to strong cancer pain. Advances in human genome research have fueled a growing interest to understand individual differences in responsiveness to opioid analgesics. This study aimed to explore and identify novel loci for genes predisposing an individual to opioid analgesic responsiveness...
September 14, 2018: Neuropsychopharmacology reports
Kun Lv, Wenwen Song, Rui Tang, Zhiyong Pan, Yong Zhang, Yi Xu, Bin Lv, Yihong Fan, Maosheng Xu
PURPOSE: Crohn's disease (CD) has been known to cause both abdominal pain alongside functional and structural alterations in the central nervous system (CNS) in affected patients. This study seeks to determine the alternations of metabolites in the bilateral anterior cingulate cortex (ACC) of CD patients with abdominal pain by using proton magnetic resonance spectroscopy (1 H-MRS) to further explore the neural mechanism. METHODS: Sixteen CD patients with abdominal pain and 13 CD patients without abdominal pain, were recruited alongside 20 healthy controls (HCs) for this study...
2018: NeuroImage: Clinical
Sampurna Chakrabarti, Luke A Pattison, Kaajal Singhal, James R F Hockley, Gerard Callejo, Ewan St John Smith
Ongoing, spontaneous pain is characteristic of inflammatory joint pain and reduces an individual's quality of life. To understand the neural basis of inflammatory joint pain, we made a unilateral knee injection of complete Freund's adjuvant (CFA) in mice, which reduced their natural digging behavior. We hypothesized that sensitization of knee-innervating dorsal root ganglion (DRG) neurons underlies this altered behavior. To test this hypothesis, we performed electrophysiological recordings on retrograde labeled knee-innervating primary DRG neuron cultures and measured their responses to a number of electrical and chemical stimuli...
December 2018: Neuropharmacology
Tobias Schmidt, Nikoo Ghaffarian, Camille Philippot, Gerald Seifert, Christian Steinhäuser, Hans-Christian Pape, Peter Blaesse
The thalamus is important for sensory integration with the ventrobasal thalamus (VB) as relay controlled by GABAergic projections from the nucleus reticularis thalami (NRT). Depending on the [Cl- ]i primarily set by cation-chloride-cotransporters, GABA is inhibitory or excitatory. There is evidence that VB and NRT differ in terms of GABA action, with classical hyperpolarization in VB due to the expression of the Cl- extruder KCC2 and depolarizing/excitatory GABA action in the NRT, where KCC2 expression is low and Cl- accumulation by the Cl- inward transporter NKCC1 has been postulated...
September 17, 2018: Scientific Reports
Min Xu, David L H Bennett, Luis Antonio Querol, Long-Jun Wu, Sarosh R Irani, James C Watson, Sean J Pittock, Christopher J Klein
The immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important- in pain modulation. The result of these interactions is central and peripheral sensitisation of nociceptive processing. Additionally, new insights and the term 'autoimmune pain' have emerged through discovery of specific IgGs targeting the extracellular domains of antigens at nodal and synaptic structures, causing pain directly without inflammation by enhancing neuronal excitability...
September 17, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Alicja Nowaczyk, Łukasz Fijałkowski, Magdalena Kowalska, Adrian Podkowa, Kinga Sałat
In this paper, we describe the latest results involving molecular modeling and pharmacodynamic studies of the selected highly lipophilic compounds acting by human GABA transporter 1 (hGAT1) inhibition. The chemical interaction of 17 GABA analogues with a model of hGAT1 is described using the molecular docking method. The biological role of GAT1 is related to the regulation of GABA level in the central nervous system and GAT1 inhibition plays an important role in the control of seizure threshold. To confirm that GAT1 can be also a molecular target for drugs used to treat other neurological and psychiatric diseases (e...
September 28, 2018: ACS Chemical Neuroscience
Alicja Nowaczyk, Łukasz Fijałkowski, Paula Zaręba, Kinga Sałat
Inhibition of 4-aminobutanoic acid (GABA) uptake is a strategy for enhancing GABA transmission. The utility of this approach is demonstrated by the successful development of such agents for the treatment of epilepsy and pain. Existing reports on acute brain slice preparations indicate the intersecting of complementary channels and receptors sets between astrocytes and neurons cells. Thorough analysis of astroglial cells by means of molecular and functional studies demonstrated their active modulatory role in intercellular communication...
September 8, 2018: Journal of Molecular Graphics & Modelling
Timothy J Ness, Cary DeWitte, Jamie McNaught, Buffie Clodfelder-Miller, Xin Su
Bilateral electrical pudendal nerve stimulation (bPNS) reduces bladder hypersensitivity in rat models of bladder pain and anecdotally reduces pain in humans with pelvic pain of urologic origin. The spinal neurochemical mechanisms of this antinociception are unknown. In the present study, bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Visceromotor responses (VMRs; abdominal muscle contractions) to urinary bladder distension (UBD) were used as a nociceptive endpoint under urethane-isoflurane anesthesia...
November 1, 2018: Neuroscience Letters
P Balaram, T A Hackett, D B Polley
Debilitating perceptual disorders including tinnitus, hyperacusis, phantom limb pain and visual release hallucinations may reflect aberrant patterns of neural activity in central sensory pathways following a loss of peripheral sensory input. Here, we explore short- and long-term changes in gene expression that may contribute to hyperexcitability following a sudden, profound loss of auditory input from one ear. We used fluorescence in situ hybridization to quantify mRNA levels for genes encoding AMPA and GABAA receptor subunits (Gria2 and Gabra1, respectively) in single neurons from the inferior colliculus (IC) and auditory cortex (ACtx)...
September 1, 2018: Neuroscience
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