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Pathophysiology of Pain

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36 papers 0 to 25 followers
By Xander Zuidema MD, pharmD, Anesthesiologist, intensivist, pain specialist
https://www.readbyqxmd.com/read/28418213/pain-thresholds-supra-threshold-pain-and-lidocaine-sensitivity-in-patients-with-erythromelalgia-including-the-i848tmutation-in-nav-1-7
#1
T Helås, D Sagafos, I P Kleggetveit, H Quiding, B Jönsson, M Segerdahl, Z Zhang, H Salter, M Schmelz, E Jørum
OBJECTIVES: Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM). METHODS: Lidocaine (0.25, 0.50, 1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful areas of the lower arm, in a randomized, double-blind manner, to test the effect on dynamic and static mechanical sensitivity, mechanical pain sensitivity, thermal thresholds and supra-threshold heat pain sensitivity...
April 18, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28422818/inhibition-of-metabotropic-glutamate-receptor-subtype-1-alters-the-excitability-of-the-commissural-pyramidal-neuron-in-the-rat-anterior-cingulate-cortex-after-chronic-constriction-injury-to-the-sciatic-nerve
#2
Shi-Hao Gao, Lin-Lin Shen, Hui-Zhong Wen, Yan-Dong Zhao, Huai-Zhen Ruan
BACKGROUND: Inhibition of the metabotropic glutamate receptor subtype 1 in the anterior cingulate cortex has an analgesic effect during sustained nociceptive hypersensitivity. However, the specific changes in different subtypes of anterior cingulate cortex layer 5 pyramidal neurons, as well as the distinct effect of metabotropic glutamate receptor subtype 1 inhibition on different neuronal subtypes, have not been well studied. METHODS: Retrograde labeling combined with immunofluorescence, whole cell clamp recording, and behavioral tests combined with RNA interference were performed in a rat model of chronic constriction injury to the sciatic nerve...
April 19, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28400293/the-dorsolateral-prefrontal-cortex-in-acute-and-chronic-pain
#3
David A Seminowicz, Massieh Moayedi
The dorsolateral prefrontal cortex (DLPFC) is a functionally and structurally heterogeneous region and a key node of several brain networks, implicated in cognitive, affective, and sensory processing. As such, the DLPFC is commonly activated in experimental pain studies, and shows abnormally increased function in chronic pain populations. Furthermore, several studies have shown that some chronic pains are associated with decreased left DLPFC gray matter and that successful interventions can reverse this structural abnormality...
April 8, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28403399/the-role-of-microglia-in-the-pathobiology-of-neuropathic-pain-development-what-do-we-know
#4
H Zhao, A Alam, Q Chen, M A Eusman, A Pal, S Eguchi, L Wu, D Ma
Neuropathic pain, a maladaptive and chronic condition that can develop after a lesion or disease affecting the somatosensory system, is characterized by allodynia, hyperalgesia and spontaneous pain, and comorbidities such as sleep deprivation, depression and anxiety. The activation of microglial cells in response to nerve injury has been implicated in the development of neuropathic pain. Mediators such as Neuregulin-1, matrix metalloproteinase (MMP)-2, MMP-9, The chemokine (C-C motif) ligand 2 (CCL2) and fractalkine are released after nerve injury and are involved in the activation of microglial cells...
April 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28394828/rab7-a-novel-redox-target-that-modulates-inflammatory-pain-processing
#5
Wiebke Kallenborn-Gerhardt, Christine V Möser, Jana E Lorenz, Mirco Steger, Juliana Heidler, Reynir Scheving, Jonas Petersen, Lea Kennel, Cathrin Flauaus, Ruirui Lu, Aimee L Edinger, Irmgard Tegeder, Gerd Geisslinger, Heinrich Heide, Ilka Wittig, Achim Schmidtko
Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice...
April 7, 2017: Pain
https://www.readbyqxmd.com/read/28394854/a-role-for-nk-1-neurons-in-the-rostral-ventromedial-medulla-in-the-development-of-chronic-post-thoracotomy-pain
#6
Sergey G Khasabov, Jeffrey Chi-Fei Wang, Donald A Simone, Gary R Strichartz
Thoracotomy results in chronic post-operative pain (CPTP) in half of the cases. Earlier findings in rat models of persistent post-surgical pain suggest that spinal pathways are critical for pain onset but not its maintenance. Descending systems from the brain stem modulate nociceptive transmission in the spinal cord and contribute to persistent pain, but their role in chronic postoperative pain has not been studied. Here we ablated pronociceptive neurokinin-1 receptor (NK-1R)-expressing neurons in the rat rostral ventromedial medulla (RVM) to identify their role in CPTP...
April 5, 2017: Pain
https://www.readbyqxmd.com/read/28340290/nucleus-accumbens-dopamine-receptors-mediate-hypothalamus-induced-antinociception-in-the-rat-formalin-test
#7
A Siahposht-Khachaki, P Pourreza, S Ezzatpanah, A Haghparast
BACKGROUND: Lateral hypothalamus (LH) involves in modulation of tonic pain. Regarding the direct and indirect neural connections between the LH and nucleus accumbens (NAc), we aimed to examine the pain modulatory role of NAc dopamine receptors in modulation of LH-induced analgesia in the formalin test. METHODS: Vehicle-control groups received saline or DMSO into the NAc and saline into the LH. Carbachol-control groups received carbachol (250 nmol/L) into the LH, 5 min after saline or DMSO injection into the NAc...
March 24, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28301400/the-role-of-calcitonin-gene-related-peptide-in-peripheral-and-central-pain-mechanisms-including-migraine
#8
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
#9
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
#10
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 U.S. 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 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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 shown that spinal sigma-1 receptor (Sig-1R) activation facilitates nociception via an increase in phosphorylation of the N-methyl-D-aspartate (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 after chronic constriction injury (CCI) of the sciatic nerve. Intrathecal administration of the D-serine degrading enzyme, D-amino acid oxidase attenuated the facilitation of NMDA-induced nociception induced by the Sig-1R agonist, 2-(4-morpholinethyl)1-phenylcyclohexane carboxylate...
December 14, 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
#20
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...
May 2017: European Journal of Pain: EJP
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