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Pathophysiology of Pain

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By Xander Zuidema MD, pharmD, Anesthesiologist, intensivist, pain specialist
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), anicotinamide adenosine 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 down-regulated significantly in high-fat-fed/low-dose STZ-induced neuropathic pain rats...
September 29, 2016: Pain
Chia-Kai Liu, Wen-Tzu Liao, Yu-Chi Chu, Chien-Hui Yang, Kuan-Hung Chen, Chih-Hsien Wu, Chung-Ren Lin
BACKGROUND:  Pulsed radiofrequency (PRF) treatment offers pain relief for patients suffering from chronic pain who do not respond well to conventional treatments. We tested whether PRF treatment attenuated complete Freund's adjuvant (CFA)-induced inflammatory pain. Epigenetic modification of potassium-chloride cotransporter 2 (KCC2) gene expression was examined to elucidate the potential contributing mechanism. METHODS:  Male Sprague-Dawley rats were injected with CFA into the plantar surface of the left hind paw to induce inflammation...
September 28, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Ke Wang, Ziyong Ju, Yue Yong, Tongyu Chen, Jiangang Song, Jia Zhou
BACKGROUND: Electroacupuncture (EA) is widely applied for pain management, but the analgesic effects of EA have not been fully elucidated. In this study, we investigated the effect of EA on inflammatory pain caused by intraplantar injection of complete Freund's adjuvant (CFA) and apelin/APJ expression in the spinal cord of rats. METHODS: The study was conducted in 3 parts. In part 1, Sprague-Dawley rats were divided into 4 groups (n = 10): sham, CFA, EA (CFA + 2 Hz EA at acupoints), and NA-EA (CFA + acupuncture without electrical stimulation)...
September 13, 2016: Anesthesia and Analgesia
Koji Shibasaki
This review provides a summary of the physiological significance of the TRPV4 ion channel. Although TRPV4 was initially characterized as an osmosensor, we found that TRPV4 can also act as a thermosensor or a mechanosensor in brain neurons or epithelial cells in the urinary bladder. Here, we summarize the newly characterized functions of TRPV4, including the research progress that has been made toward our understanding of TRPV4 physiology, and discuss other recent data pertaining to TRPV4. It is thought that TRPV4 may be an important drug target based on its broad expression patterns and important physiological functions...
August 9, 2016: Journal of Anesthesia
C-R Lin, J-K Cheng, C-H Wu, K-H Chen, C-K Liu
BACKGROUND: Multiple mechanisms contribute to the stimulus-evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain. METHODS: Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats...
August 10, 2016: European Journal of Pain: EJP
Paul D Whissell, Sinziana Avramescu, Dian-Shi Wang, Beverley A Orser
BACKGROUND: Extrasynaptic γ-aminobutyric acid type A (GABAA) receptors that contain the δ subunit (δGABAA receptors) contribute to memory performance. Dysregulation of δGABAA receptor expression, which occurs in some neurological disorders, is associated with memory impairment. Mice lacking δGABAA receptors (Gabrd) exhibit deficits in their ability to distinguish between similar memories, a process which is referred to as pattern separation. The CA3 and dentate gyrus subfields of the hippocampus regulate pattern separation, raising the possibility that synaptic plasticity is impaired in these regions in Gabrd mice...
July 26, 2016: Anesthesia and Analgesia
Brian W LeBlanc, Paul M Bowary, Yu-Chieh Chao, Theresa R Lii, Carl Y Saab
Pain modulates rhythmic neuronal activity recorded by Electroencephalography (EEG) in humans. Our laboratory previously showed that rat models of acute and neuropathic pain manifest increased power in primary somatosensory cortex (S1) recorded by electrocorticography (ECoG). In this study, we hypothesized that pain increases EEG power and corticocortical coherence in different rat models of pain, whereas treatments with clinically effective analgesics reverse these changes. Our results show increased cortical power over S1 and prefrontal cortex (PFC) in awake, freely behaving rat models of acute, inflammatory and neuropathic pain...
October 2016: Pain
Dagrun Sagafos, Inge P Kleggetveit, Tormod Helås, Roland Schmidt, Jan Minde, Barbara Namer, Martin Schmelz, Ellen Jørum
OBJECTIVES: Nerve growth factor (NGF) is a protein important for growth and survival, but also for modulation of sensitivity of nociceptors and sympathetic neurons. The purpose of the present study was to investigate the effects of reduced NGF signaling in patients with hereditary sensory and autonomic neuropathies type V, congenital insensitivity to pain, caused by a mutation of the NGFβ gene, including a characterization of single nociceptive fibers using microneurography (MNG). MATERIALS AND METHODS: One homozygote and 2 heterozygote patients with this mutation were examined with electromyography/neurography, thermal testing, quantitative sudomotor axon reflex test, and electrically induced axon reflex erythema in addition to MNG...
July 2016: Clinical Journal of Pain
David A Fishbain, Aditya Pulikal, John E Lewis, Jinrun Gao
OBJECTIVES: The hypotheses of this systematic review were the following: 1) Prevalence of post-traumatic stress disorder (PTSD) will differ between various types of chronic pain (CP), and 2) there will be consistent evidence that CP is associated with PTSD. METHODS: Of 477 studies, 40 fulfilled the inclusion/exclusion criteria of this review and were grouped according to the type of CP. The reported prevalence of PTSD for each grouping was determined by aggregating all the patients in all the studies in that group...
May 17, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Alexander M Binshtok, Bruce P Bean, Clifford J Woolf
Most local anaesthetics used clinically are relatively hydrophobic molecules that gain access to their blocking site on the sodium channel by diffusing into or through the cell membrane. These anaesthetics block sodium channels and thereby the excitability of all neurons, not just sensory neurons. We tested the possibility of selectively blocking the excitability of primary sensory nociceptor (pain-sensing) neurons by introducing the charged, membrane-impermeant lidocaine derivative QX-314 through the pore of the noxious-heat-sensitive TRPV1 channel...
October 4, 2007: Nature
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