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Pathophysiology of Pain

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29 papers 0 to 25 followers
By Xander Zuidema MD, pharmD, Anesthesiologist, intensivist, pain specialist
https://www.readbyqxmd.com/read/28301400/the-role-of-calcitonin-gene-related-peptide-in-peripheral-and-central-pain-mechanisms-including-migraine
#1
Smriti Iyengar, Michael H Ossipov, Kirk W Johnson
Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene-related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently...
April 2017: Pain
https://www.readbyqxmd.com/read/28263013/slow-brushing-reduces-heat-pain-in-humans
#2
J Liljencrantz, I Strigo, D M Ellingsen, H H Krämer, L C Lundblad, S S Nagi, S Leknes, H Olausson
BACKGROUND: C-tactile (CT) afferents are unmyelinated low-threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation. METHODS: In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub-optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain...
March 6, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28254585/the-potential-role-of-sensory-testing-skin-biopsy-and-functional-brain-imaging-as-biomarkers-in-chronic-pain-clinical-trials-immpact-considerations
#3
REVIEW
Shannon M Smith, Robert H Dworkin, Dennis C Turk, Ralf Baron, Michael Polydefkis, Irene Tracey, David Borsook, Robert R Edwards, Richard E Harris, Tor D Wager, Lars Arendt-Nielsen, Laurie B Burke, Daniel B Carr, Amy Chappell, John T Farrar, Roy Freeman, Ian Gilron, Veeraindar Goli, Juergen Haeussler, Troels Jensen, Nathaniel P Katz, Jeffrey Kent, Ernest A Kopecky, David A Lee, William Maixner, John D Markman, Justin C McArthur, Michael P McDermott, Lav Parvathenani, Srinivasa N Raja, Bob A Rappaport, Andrew S C Rice, Michael C Rowbotham, Jeffrey K Tobias, Ajay D Wasan, James Witter
Valid and reliable biomarkers can play an important role in clinical trials as indicators of biological or pathogenic processes or as a signal of treatment response. Currently, there are no biomarkers for pain qualified by the US Food and Drug Administration or the European Medicines Agency for use in clinical trials. This article summarizes an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting in which 3 potential biomarkers were discussed for use in the development of analgesic treatments: (1) sensory testing, (2), skin punch biopsy, and (3) brain imaging...
February 27, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28244951/the-role-of-nr2b-creb-mir212-132-crtc1-creb-signal-network-in-pain-regulation-in-vitro-and-in-vivo
#4
Tianjiao Xia, Shuaishuai Chu, Yin Cui, Fangxia Xu, Yue Liu, Jia Song, Yue Qian, Xueming Shao, Xiuxiu Li, Xiaoping Gu, Zhengliang Ma
BACKGROUND: Chronic pain is a debilitating threat to human health, and its molecular mechanism remains undefined. Previous studies have illustrated a key role of cAMP response element-binding protein (CREB) in pain regulation; CREB-regulated transcription coactivator 1 (CRTC1) and microRNA212/132 (miR212/132) are also vital in synaptic plasticity. However, little is known about the interaction among these factors in pain condition. We conducted this experiment mainly to determine the crosstalk between CREB, CRTC1, and miR212/132 in vitro...
February 24, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28225710/chronic-stress-exacerbates-neuropathic-pain-via-the-integration-of-stress-affect-related-information-with-nociceptive-information-in-the-central-nucleus-of-the-amygdala
#5
Ming-Jia Li, Ling-Yu Liu, Lin Chen, Jie Cai, You Wan, Guo-Gang Xing
Exacerbation of pain by chronic stress and comorbidity of pain with stress-related psychiatric disorders, including anxiety and depression, represent significant clinical challenges. However, the underlying mechanisms still remain unclear. Here, we investigated whether chronic forced swim stress (CFSS)-induced exacerbation of neuropathic pain is mediated by the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala (CeA). We first demonstrated that CFSS indeed produces both depressive-like behaviors and exacerbation of spared nerve injury (SNI)-induced mechanical allodynia in rats...
April 2017: Pain
https://www.readbyqxmd.com/read/28225715/the-role-of-cgrp-in-peripheral-and-central-pain-mechanisms-including-migraine
#6
Smriti Iyengar, Michael H Ossipov, Kirk W Johnson
Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. CGRP was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain...
December 29, 2016: Pain
https://www.readbyqxmd.com/read/28114184/pain-has-an-element-of-blank-a-biobehavioral-approach-to-chronicity
#7
Herta Flor
No abstract text is available yet for this article.
April 2017: Pain
https://www.readbyqxmd.com/read/28129218/neurobiological-basis-for-pain-vulnerability-why-me
#8
Franziska Denk, Stephen B McMahon
No abstract text is available yet for this article.
April 2017: Pain
https://www.readbyqxmd.com/read/28072604/epigenetic-upregulation-of-cxcl12-expression-mediates-antitubulin-chemotherapeutics-induced-neuropathic-pain
#9
Ting Xu, Xiao-Long Zhang, Han-Dong Ou-Yang, Zhen-Yu Li, Cui-Cui Liu, Zhen-Zhen Huang, Jing Xu, Jia-You Wei, Bi-Lin Nie, Chao Ma, Shao-Ling Wu, Wen-Jun Xin
Clinically, Microtubule-targeted agents-induced neuropathic pain hampers chemotherapeutics for patients with cancer. Here, we found that application of paclitaxel or vincristine increased the protein and mRNA expression of CXCL12 and frequency and amplitude of miniature excitatory post synaptic currents (mEPSCs) in spinal dorsal horn neurons. Spinal local application of CXCL12 induced the long-term potentiation of nociceptive synaptic transmission and increased the amplitude of mEPSCs. Inhibition of CXCL12 using the transgenic mice (CXCL12) or neutralizing antibody or siRNA ameliorated the mEPSC's enhancement and mechanical allodynia...
April 2017: Pain
https://www.readbyqxmd.com/read/28030472/epigenetic-divergence-in-the-trpa1-promoter-correlates-with-pressure-pain-thresholds-in-healthy-individuals
#10
Sara Gombert, Mathias Rhein, Mirjam Eberhardt, Tino Münster, Stefan Bleich, Andreas Leffler, Helge Frieling
The expression pattern of important transduction molecules in nociceptive sensory neurons is likely to dictate pain sensitivity. While this notion is well established for increased pain sensitivities under conditions like inflammation and neuropathy, less is known as to which molecules are defining interindividual differences in pain sensitivity in healthy subjects. A genome-wide methylation analysis on monozygotic twins found that methylation of a CpG dinucleotide in the promoter of transient receptor potential ankyrin 1 (TRPA1) is inversely associated with the threshold for heat-induced pain...
April 2017: Pain
https://www.readbyqxmd.com/read/28009628/enhanced-delivery-of-il-1-receptor-antagonist-to-the-central-nervous-system-as-a-novel-anti-transferrin-receptor-il-1ra-fusion-reverses-neuropathic-mechanical-hypersensitivity
#11
Carl I Webster, Jon Hatcher, Matthew Burrell, George Thom, Peter Thornton, Ian Gurrell, Iain Chessell
Neuropathic pain is a major unmet medical need, with only 30% to 35% of patients responding to the current standard of care. The discovery and development of novel therapeutics to address this unmet need have been hampered by poor target engagement, the selectivity of novel molecules, and limited access to the relevant compartments. Biological therapeutics, either monoclonal antibodies (mAbs) or peptides, offer a solution to the challenge of specificity as the intrinsic selectivity of these kinds of molecules is significantly higher than traditional medicinal chemistry-derived approaches...
April 2017: Pain
https://www.readbyqxmd.com/read/27986591/spinal-d-serine-increases-pkc-dependent-glun1-phosphorylation-contributing-to-the-sigma-1-receptor-induced-development-of-mechanical-allodynia-in-a-mouse-model-of-neuropathic-pain
#12
Sheu-Ran Choi, Ji-Young Moon, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Hoon-Seong Choi, Suk-Yun Kang, Ho-Jae Han, Alvin J Beitz, Jang-Hern Lee
We have recently demonstrated that spinal sigma-1 receptor (Sig-1R) activation facilitates nociception via an increase in phosphorylation of the NMDA receptor GluN1 subunit (pGluN1). The present study was designed to examine whether the Sig-1R-induced facilitative effect on NMDA-induced nociception is mediated by D-serine, and whether D-serine modulates spinal pGluN1 expression and the development of neuropathic pain following chronic constriction injury (CCI) of the sciatic nerve. Intrathecal administration of the D-serine degrading enzyme, DAAO attenuated the facilitation of NMDA-induced nociception induced by the Sig-1R agonist, PRE084...
December 13, 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/27977070/role-of-transient-receptor-potential-ankyrin-1-receptors-in-rodent-models-of-meningeal-nociception-experiments-in%C3%A2-vitro
#13
A C Denner, B Vogler, K Messlinger, R De Col
BACKGROUND: The TRP channel ankyrin type 1 (TRPA1) is a nonselective cation channel known to be activated by environmental irritants, cold and endogenous mediators of inflammation. Activation of TRPA1 in trigeminal afferents innervating meningeal structures has recently been suggested to be involved in the generation of headaches. METHODS: Two in vitro models of meningeal nociception were employed using the hemisected rodent head preparation, (1) recording of single meningeal afferents and (2) release of calcitonin gene-related peptide (CGRP) from the cranial dura mater...
December 15, 2016: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/27956668/the-inflammasome-as-a-target-for-pain-therapy
#14
H Zhang, F Li, W-W Li, C Stary, J D Clark, S Xu, X Xiong
The interleukin-1 family of cytokines are potent inducers of inflammation and pain. Proteolytic activation of this family of cytokines is under the control of several innate immune receptors that coordinate to form large multiprotein signalling platforms, termed inflammasomes. Recent evidence suggests that a wide range of inflammatory diseases, cancers, and metabolic and autoimmune disorders, in which pain is a common complaint, may be coordinated by inflammasomes. Activation of inflammasomes results in cleavage of caspase-1, which subsequently induces downstream initiation of several potent pro-inflammatory cascades...
December 2016: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/27902570/preprotachykinin-a-is-expressed-by-a-distinct-population-of-excitatory-neurons-in-the-mouse-superficial-spinal-dorsal-horn-including-cells-that-respond-to-noxious-and-pruritic-stimuli
#15
Maria Gutierrez-Mecinas, Andrew M Bell, Alina Marin, Rebecca Taylor, Kieran A Boyle, Takahiro Furuta, Masahiko Watanabe, Erika Polgár, Andrew J Todd
The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined 3 nonoverlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B, and gastrin-releasing peptide. Here we identify and characterise another population: neurons that express the tachykinin peptide substance P...
March 2017: Pain
https://www.readbyqxmd.com/read/27908839/the-transition-of-acute-postoperative-pain-to-chronic-pain-an-integrative-overview-of-research-on-mechanisms
#16
C Richard Chapman, Charles J Vierck
The nature of the transition from acute to chronic pain still eludes explanation, but chronic pain resulting from surgery provides a natural experiment that invites both clinical epidemiological investigation and basic scientific inquiry into the mechanisms of this transition. The primary purpose of this paper is to review current knowledge and hypotheses on the transition from acute to persistent postsurgical pain, summarizing literature on clinical epidemiological studies of persistent postsurgical pain development, as well as basic neurophysiological studies targeting mechanisms in the periphery, spinal cord, and brain...
November 28, 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/27842048/camkii%C3%AE-underlies-spontaneous-and-evoked-pain-behaviors-in-berkeley-sickle-cell-transgenic-mice
#17
Ying He, Yan Chen, Xuebi Tian, Cheng Yang, Jian Lu, Chun Xiao, Joseph DeSimone, Diana J Wilkie, Robert E Molokie, Zaijie Jim Wang
Pain is one of the most challenging and stressful conditions to patients with sickle cell disease (SCD) and their clinicians. Patients with SCD start experiencing pain as early as 3 months old and continue having it throughout their lives. Although many aspects of the disease are well understood, little progress has been made in understanding and treating pain in SCD. This study aimed to investigate the functional involvement of Ca/calmodulin-dependent protein kinase II (CaMKIIα) in the persistent and refractory pain associated with SCD...
December 2016: Pain
https://www.readbyqxmd.com/read/27849648/amygdala-mediated-mechanisms-regulate-visceral-hypersensitivity-in-adult-females-following-early-life-stress-importance-of-the-glucocorticoid-receptor-and-corticotropin-releasing-factor
#18
Dawn K Prusator, Beverley Greenwood-Van Meerveld
Alterations in amygdala activity are apparent in women who report a history of early life stress (ELS) as well as those diagnosed with chronic pain disorders. Chronic stress in adulthood induces visceral hypersensitivity via alterations in glucocorticoid receptor (GR) and corticotropin-releasing factor (CRF) expression within the central amygdala (CeA). Here we hypothesized that unpredictable ELS, previously shown to induce visceral hypersensitivity in adult female rats, alters GR and CRF expression in the CeA...
November 14, 2016: Pain
https://www.readbyqxmd.com/read/27807916/alpha-range-visual-and-auditory-stimulation-reduces-the-perception-of-pain
#19
K Ecsy, A K P Jones, C A Brown
BACKGROUND: Alpha power is believed to have an inverse relationship with the perception of pain. Increasing alpha power through an external stimulus may, therefore, induce an analgesic effect. Here, we attempt to modulate the perception of a moderately painful acute laser stimulus by separately entraining three frequencies across the alpha band: 8, 10 and 12 Hz. METHODS: Participants were exposed to either visual or auditory stimulation at three frequencies in the alpha-band range and a control frequency...
March 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/27749604/sirt1-attenuates-neuropathic-pain-by-epigenetic-regulation-of-mglur1-5-expressions-in-type-2-diabetic-rats
#20
Cheng-Hua Zhou, Ming-Xing Zhang, Sha-Sha Zhou, Huan Li, Jian Gao, Lei Du, Xiao-Xing Yin
Accumulating evidence has demonstrated that epigenetic modification-mediated changes in pain-related gene expressions play an important role in the development and maintenance of neuropathic pain. Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is involved in the development of chronic pain. Moreover, SIRT1 may be a novel therapeutic target for the prevention of type 2 diabetes mellitus (T2DM). But the role of SIRT1 in T2DM-induced neuropathic pain remains unknown. In this study, we found that spinal SIRT1 expression and activity were downregulated significantly in high-fat-fed/low-dose streptozotocin-induced neuropathic pain rats...
January 2017: Pain
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