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Pathophysiology of Pain

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66 papers 0 to 25 followers
By Xander Zuidema MD, pharmD, Anesthesiologist, intensivist, pain specialist
https://www.readbyqxmd.com/read/28902684/estrogens-synthesized-and-acting-within-a-spinal-oligomer-suppress-spinal-endomorphin-2-antinociception-ebb-and-flow-over-the-rat-reproductive-cycle
#1
Nai-Jiang Liu, Vijaya Murugaiyan, Emiliya M Storman, Stephen A Schnell, Martin W Wessendorf, Alan R Gintzler
The magnitude of antinociception elicited by intrathecal endomorphin 2 (EM2), an endogenous mu-opioid receptor (MOR) ligand, varies across the rat estrous cycle. We now report that phasic changes in analgesic responsiveness to spinal EM2 result from plastic interactions within a novel membrane-bound oligomer containing estrogen receptors (mERs), aromatase (aka estrogen synthase), metabotropic glutamate receptor 1 (mGluR1), and MOR. During diestrus, spinal mERs, activated by locally synthesized estrogens, act with mGluR1 to suppress spinal EM2/MOR antinociception...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28898500/offset-analgesia-the-role-of-peripheral-and-central-mechanisms
#2
D Ligato, K K Petersen, C D Mørch, L Arendt-Nielsen
BACKGROUND: Offset Analgesia (OA) can be evoked by a three-heat-stimulus train (T1-T2-T3), with T1 (5 s) and T3 (20 s) having the same temperature (e.g. 48 °C) and T2 (5 s) being slightly higher (1-3 °C). OA is defined as a disproportional pain reduction caused by the slight temperature decrease from T2 to T3. As the pain modulatory mechanisms behind OA are still poorly understood, the current study aimed to investigate the role of peripheral and central mechanisms by applying heat stimuli to the same location and to different unilateral and bilateral locations...
September 12, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28885453/peripheral-afferents-and-spinal-inhibitory-system-in-dynamic-and-static-mechanical-allodynia
#3
Jun-Ho La, Jin Mo Chung
No abstract text is available yet for this article.
September 1, 2017: Pain
https://www.readbyqxmd.com/read/28847735/loss-of-temporal-inhibition-of-nociceptive-information-is-associated-with-aging-and-bodily-pain
#4
Kelly M Naugle, Yenisel Cruz-Almeida, Roger B Fillingim, Joseph L Riley
An age-related decline in endogenous pain inhibitory processes likely places older adults at an increased risk for chronic pain. Limited research indicates that older adults may be characterized by deficient offset analgesia, an inhibitory temporal sharpening mechanism that increases the detectability of minor decreases in noxious stimulus intensity. The primary purpose of the study was to examine age differences in offset analgesia in community-dwelling younger, middle-aged, and older adults. An additional aim of the study was to determine whether the magnitude of offset analgesia predicted self-reported bodily pain...
August 25, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28837503/therapeutic-potential-for-leukocyte-elastase-in-chronic-pain-states-harboring-a-neuropathic-component
#5
Kiran Kumar Bali, Rohini Kuner
Neuropathic pain is an integral component of several chronic pain conditions and poses a major health problem worldwide. Despite emerging understanding of mechanisms behind neuropathic pain, the available treatment options are still limited in efficacy or associated with side effects, therefore making it necessary to find viable alternatives. In a genetic screen, we recently identified SerpinA3N, a serine protease inhibitor secreted in response to nerve damage by the DRG neurons and we showed that SerpinA3N acts against induction of neuropathic pain by inhibiting the T-cell- and neutrophil-derived protease, leucocyte elastase (LE)...
August 19, 2017: Pain
https://www.readbyqxmd.com/read/28809766/crispr-cas9-editing-of-nf1-gene-identifies-crmp2-as-a-therapeutic-target-in-neurofibromatosis-type-1-nf1-related-pain-that-is-reversed-by-s-lacosamide
#6
Aubin Moutal, Xiaofang Yang, Wennan Li, Kerry B Gilbraith, Shizhen Luo, Song Cai, Liberty François-Moutal, Lindsey A Chew, Seul Ki Yeon, Shreya S Bellampalli, Chaoling Qu, Jennifer Y Xie, Mohab M Ibrahim, May Khanna, Ki Duk Park, Frank Porreca, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. NF1 patients commonly experience severe pain. Studies on mice with Nf1 haploinsufficiency have been instructive in identifying sensitization of ion channels as a possible cause underlying the heightened pain suffered by NF1 patients. However, behavioral assessments of Nf1+/- mice have led to uncertain conclusions about the potential causal role of Nf1 in pain. We used the clustered regularly interspaced short palindromic repeats/(CRISPR)-associated 9 (CRISPR/Cas9) genome editing system to create and mechanistically characterize a novel rat model of NF1-related pain...
July 3, 2017: Pain
https://www.readbyqxmd.com/read/28817416/nicotinic-modulation-of-descending-pain-control-circuitry
#7
Iboro C Umana, Claire A Daniele, Brooke A Miller, Keith Gallagher, Meghan A Brown, Chandrika Abburi, Peggy Mason, Daniel S McGehee
Along with the well-known rewarding effects, activation of nicotinic acetylcholine receptors (nAChRs) can also relieve pain, and some nicotinic agonists have analgesic efficacy similar to opioids. A major target of analgesic drugs is the descending pain modulatory pathway, including the ventrolateral periaqueductal gray (vlPAG) and the rostral ventromedial medulla (RVM). Although activating nAChRs within this circuitry can be analgesic, little is known about the subunit composition and cellular effects of these receptors, particularly within the vlPAG...
July 3, 2017: Pain
https://www.readbyqxmd.com/read/28809075/allosteric-modulation-of-%C3%AE-4%C3%AE-2-nicotinic-acetylcholine-receptors-desformylflustrabromine-potentiates-antiallodynic-response-of-nicotine-in-a-mouse-model-of-neuropathic-pain
#8
D Bagdas, D Ergun, A Jackson, W Toma, M K Schulte, M I Damaj
BACKGROUND: Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels. The α4β2 subtype of nAChRs plays an important role in the mediation of pain and several nicotine-evoked responses. Agonists and partial agonists of α4β2 nAChRs show efficacy in animal pain models. In addition, the antinociceptive properties of nicotine, a non-selective nAChR agonist with a high affinity for α4β2 nAChRs, is well-known. There is a growing body of evidence pointing to allosteric modulation of nAChRs as an alternative treatment strategy in experimental pain...
August 14, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28806222/transient-receptor-potential-vanilloid-1-antagonists-prevent-anesthesia-induced-hypothermia-and-decrease-postincisional-opioid-dose-requirements-in-rodents
#9
Andras Garami, Mohab Ibrahim, Kerry Gilbraith, Rajesh Khanna, Eszter Pakai, Alexandra Miko, Erika Pinter, Andrej A Romanovsky, Frank Porreca, Amol M Patwardhan
BACKGROUND: Intraoperative hypothermia and postoperative pain control are two important clinical challenges in anesthesiology. Transient receptor potential vanilloid 1 has been implicated both in thermoregulation and pain. Transient receptor potential vanilloid 1 antagonists were not advanced as analgesics in humans in part due to a side effect of hyperthermia. This study tested the hypothesis that a single, preincision injection of a transient receptor potential vanilloid 1 antagonist could prevent anesthesia-induced hypothermia and decrease the opioid requirement for postsurgical hypersensitivity...
August 14, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28806224/bromodomain-containing-protein-4-activates-voltage-gated-sodium-channel-1-7-transcription-in-dorsal-root-ganglia-neurons-to-mediate-thermal-hyperalgesia-in-rats
#10
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Hsueh-Hsiao Wang, An-Sheng Lee, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
BACKGROUND: Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. METHODS: Male Sprague-Dawley rats received hind paw injections of complete Freund's adjuvant to induce hyperalgesia. The dorsal root ganglia were examined to detect changes in bromodomain-containing protein 4 expression and the activation of genes involved in the expression of voltage-gated sodium channel 1...
August 11, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28787346/antiallodynic-effects-of-endomorphin-1-and-endomorphin-2-in-the-spared-nerve-injury-model-of-neuropathic-pain-in-mice
#11
Chang-Lin Wang, Dai-Jun Yang, Bi-Yu Yuan, Ting-Ting Qiu
BACKGROUND: The spared nerve injury (SNI) model is a new animal model that can mimic several characteristics of clinical neuropathic pain. Opioids are recommended as treatment of neuropathic pain. Therefore, the present study was conducted to investigate the antinociceptive effects of endomorphin-1 (EM-1) and endomorphin-2 (EM-2) given centrally and peripherally in the SNI model of neuropathic pain in mice. METHODS: The SNI model was made in mice by sparing the sural nerve intact, when the other 2 of 3 terminal branches of the sciatic nerve (common peroneal and tibial nerves) were tightly ligated and cut...
August 4, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28767505/age-dependent-plasticity-in-endocannabinoid-modulation-of-pain-processing-through-postnatal-development
#12
Charlie H-T Kwok, Ian M Devonshire, Amer Imraish, Charles M Greenspon, Stevie Lockwood, Catherine Fielden, Andrew Cooper, Stephen Woodhams, Sarir Sarmad, Catherine A Ortori, David A Barrett, David Kendall, Andrew J Bennett, Victoria Chapman, Gareth J Hathway
Significant age and experience-dependent remodelling of spinal and supraspinal neural networks occur resulting in altered pain responses in early life. In adults endogenous opioid peptide and endocannabinoid (ECs) pain control systems exist which modify pain responses but the role they play in acute responses to pain and postnatal neurodevelopment is unknown. Here we have studied the changing role of the ECs in brainstem nuclei essential for the control of nociception from birth to adulthood in both rat and human...
August 1, 2017: Pain
https://www.readbyqxmd.com/read/28746078/spinal-microglia-are-required-for-long-term-maintenance-of-neuropathic-pain
#13
Stefania Echeverry, Xiang Qun Shi, Mu Yang, Hao Huang, YiChen Wu, Louis-Etienne Lorenzo, Jimena Perez-Sanchez, Robert P Bonin, Yves De Koninck, Ji Zhang
While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic pain at late stages remains unknown. Here, we show that microglia activation in the spinal cord persists for >3 months following nerve injury in rodents, beyond involvement of proinflammatory cytokine and chemokine signalling. In this chronic phase, selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor-TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28731982/peripheral-oxytocin-receptors-inhibit-the-nociceptive-input-signal-to-spinal-dorsal-horn-wide-dynamic-range-neurons
#14
Abimael González-Hernández, Alfredo Manzano-García, Guadalupe Martínez-Lorenzana, Irma A Tello-García, Martha Carranza, Carlos Arámburo, Miguel Condés-Lara
Oxytocin (OT) has emerged as a mediator of endogenous analgesia in behavioral and electrophysiological experiments. In fact, OT receptors (OTRs) in the spinal dorsal horn participate in a selective inhibition of the neuronal activity mediated by Aδ and C fibers but not Aβ fibers. This study shows that OTRs are expressed in the terminal nerve endings and are able to inhibit nociceptive neuronal firing. Indeed, local peripheral OT blocked the first sensorial activity of Aδ and C fibers recorded in the spinal cord neurons...
July 19, 2017: Pain
https://www.readbyqxmd.com/read/28722693/ikk-nf-%C3%AE%C2%BAb-dependent-satellite-glia-activation-induces-spinal-cord-microglia-activation-and-neuropathic-pain-after-nerve-injury
#15
Hyoungsub Lim, Hyunkyoung Lee, Kyungchul Noh, Sung Joong Lee
Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generated Ikkβ conditional knockout mice (Cnp-Cre/Ikkβ; cIkkβ) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury-induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice...
September 2017: Pain
https://www.readbyqxmd.com/read/28719507/the-relationship-between-chronic-pain-and-neurocognitive-function-a-systematic-review
#16
Diana M Higgins, Aaron M Martin, Dewleen G Baker, Jennifer J Vasterling, Victoria Risbrough
OBJECTIVE: Understanding the relationship between chronic pain and neurocognition has important implications for the assessment and treatment of pain. This paper provides an overview of the current literature examining the neurocognition-chronic pain relationship and suggests future avenues of research, along with a discussion of clinical implications of the literature findings. Consideration of potential moderators and mediators of this relationship, as well as a brief discussion of the importance of future research in special populations at particular risk for these problems, are also a focus of this paper...
July 17, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28719508/is-the-organisation-of-the-primary-motor-cortex-in-low-back-pain-related-to-pain-movement-and-or-sensation
#17
Edith Elgueta-Cancino, Siobhan Schabrun, Paul Hodges
Primary motor cortex (M1) organisation differs between individuals with and without chronic low back pain (CLBP), in parallel with motor and sensory impairments. This study investigated whether movement behaviour and tactile/pain sensation are related to M1 organisation in CLBP. Transcranial magnetic stimulation (TMS) was used to map the M1 representation of the erector spinae and multifidus muscles in 20 participants with and without CLBP. Cortical organisation was quantified by: map volume; center of gravity (CoG); number of peaks; and primary and secondary peak location...
July 17, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28715357/pain-versus-analgesia-taok3-as-a-pharmacogene
#18
Scott D Cook-Sather, Jin Li, Hakon Hakonarson
No abstract text is available yet for this article.
August 2017: Pain
https://www.readbyqxmd.com/read/28669862/spontaneous-and-bite-evoked-muscle-pain-are-mediated-by-a-common-nociceptive-pathway-with-differential-contribution-by-trpv1
#19
Sheng Wang, Jongseuk Lim, John Joseph, Sen Wang, Feng Wei, Jin Y Ro, Man-Kyo Chung
Spontaneous pain and function-associated pain are prevalent symptoms of multiple acute and chronic muscle pathologies. We established mouse models for evaluating spontaneous pain and bite-evoked pain from masseter muscle, and determined the roles of transient receptor potential cation channel subfamily V member 1 (TRPV1) and the contribution of TRPV1- or neurokinin 1 (NK1)-dependent nociceptive pathways. Masseter muscle inflammation increased Mouse Grimace Scale scores and face-wiping behavior, which were attenuated by pharmacological or genetic inhibition of TRPV1...
June 29, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28682953/role-of-sigma-1-receptor-p38-mapk-inhibition-in-acupoint-catgut-embedding-mediated-analgesic-effects-in-complete-freund-s-adjuvant-induced-inflammatory-pain
#20
Kairong Du, Xue Wang, Laiting Chi, Wenzhi Li
BACKGROUND: The endoplasmic reticulum chaperone protein Sigma-1 receptor (Sig-1 R) and mitogen-activated protein kinases (MAPKs) are involved in the mechanism of pain. Acupoint stimulation exerts an exact antihyperalgesic effect in inflammatory pain. However, whether Sig-1 R and MAPKs are associated with the acupoint stimulation-induced analgesic effects is not clear. This study investigated the analgesic effect of acupoint catgut embedding (ACE) and the inhibition of Sig-1 R and MAPKs in ACE analgesia...
August 2017: Anesthesia and Analgesia
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