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Nociceptive pain

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https://www.readbyqxmd.com/read/28644196/cebranopadol-a-novel-first-in-class-analgesic-drug-candidate-first-experience-in-patients-with-chronic-low-back-pain-in-a-randomized-clinical-trial
#1
Annette Christoph, Marie-Henriette Eerdekens, Maurits Kok, Gisela Volkers, Rainer Freynhagen
Chronic low back pain (LBP) is a common condition, usually with involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first Phase II, randomized, doubleblind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate to severe chronic LBP with and without neuropathic pain component...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28642117/soluble-epoxide-hydrolase-as-a-therapeutic-target-for-pain-inflammatory-and-neurodegenerative-diseases
#2
REVIEW
Karen M Wagner, Cindy B McReynolds, William K Schmidt, Bruce D Hammock
Eicosanoids are biologically active lipid signaling molecules derived from polyunsaturated fatty acids. Many of the actions of eicosanoid metabolites formed by cyclooxygenase and lipoxygenase enzymes have been characterized, however, the epoxy-fatty acids (EpFAs) formed by cytochrome P450 enzymes are newly described by comparison. The EpFA metabolites modulate a diverse set of physiologic functions that include inflammation and nociception among others. Regulation of EpFAs occurs primarily via release, biosynthesis and enzymatic transformation by the soluble epoxide hydrolase (sEH)...
June 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28638117/disrupted-functional-connectivity-between-the-periaqueductal-gray-and-other-brain-regions-in-a-rat-model-of-recurrent-headache
#3
Zhihua Jia, Wenjing Tang, Dengfa Zhao, Shengyuan Yu
Functional connectivity (FC) has been used to investigate the pathophysiology of migraine. We aimed to identify atypical FC between the periaqueductal gray (PAG) and other brain areas in rats induced by repeated meningeal nociception. The rat model was established by infusing an inflammatory soup (IS) through supradural catheters in conscious rats. Quiescent and face-grooming behaviors were observed to assess nociceptive behavior. FC analysis seeded on the PAG was performed on rats 21 days after IS infusion...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637974/neuron-glia-interaction-is-a-key-mechanism-underlying-persistent-orofacial-pain
#4
Koichi Iwata, Ayano Katagiri, Masamichi Shinoda
Excitability of neurons in the trigeminal ganglion (TG), trigeminal spinal subnucleus caudalis (Vc), and upper cervical spinal cord (C1-C2) is greatly enhanced after orofacial inflammation and trigeminal nerve injury, and TG, Vc, and C1-C2 neurons remain sensitized long after such episodes. Sensitized neurons generate various molecules, which are released from nociceptive neurons in these areas and are involved in modulating the excitability of TG, Vc, and C1-C2 nociceptive neurons. Hyperexcitable nociceptive neurons also activate satellite glial cells in the TG and microglial cells and astrocytes in the Vc and C1-C2...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28637600/distinguishing-between-nociceptive-and-neuropathic-components-in-chronic-low-back-pain-using-behavioural-evaluation-and-sensory-examination
#5
N Spahr, D Hodkinson, K Jolly, S Williams, M Howard, M Thacker
BACKGROUND: Diagnosis of chronic low back pain (CLBP) is traditionally predicated on identifying underlying pathological or anatomical causes, with treatment outcomes modest at best. Alternately, it is suggested that identification of underlying pain mechanisms with treatments targeted towards specific pain phenotypes may yield more success. Differentiation between nociceptive and neuropathic components of CLBP is problematic; evidence suggests that clinicians fail to identify a significant neuropathic component in many CLBP patients...
February 2017: Musculoskeletal Science & Practice
https://www.readbyqxmd.com/read/28635877/-a-neuropathic-component-of-lumboischialgia-mechanisms-of-development-and-treatment-approaches
#6
M V Churyukanov, G E Shevtsova, O I Zagorulko
Low back pain (LBP) is accompanied by the development of pain syndrome that spreads into the leg in 25-57% of patients. This is an important factor predicting the risk of transition of pain from acute to chronic and is an indirect indicator of disease severity. It is often impossible to specify the primary mechanism facilitated pain irradiation in lumboischialgia because many structures can cause analogous symptoms. Mechanisms of development of LBP are represented by nociceptive, neuropathic and psychogenic components...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28634321/a-central-mechanism-enhances-pain-perception-of-noxious-thermal-stimulus-changes
#7
B Petre, P Tetreault, V A Mathur, M W Schurgin, J Y Chiao, L Huang, A V Apkarian
Pain perception temporarily exaggerates abrupt thermal stimulus changes revealing a mechanism for nociceptive temporal contrast enhancement (TCE). Although the mechanism is unknown, a non-linear model with perceptual feedback accurately simulates the phenomenon. Here we test if a mechanism in the central nervous system underlies thermal TCE. Our model successfully predicted an optimal stimulus, incorporating a transient temperature offset (step-up/step-down), with maximal TCE, resulting in psychophysically verified large decrements in pain response ("offset-analgesia"; mean analgesia: 85%, n = 20 subjects)...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634208/ligand-and-voltage-gated-ca-2-channels-differentially-regulate-the-mode-of-vesicular-neuropeptide-release-in-mammalian-sensory-neurons
#8
Yeshi Wang, Qihui Wu, Meiqin Hu, Bin Liu, Zuying Chai, Rong Huang, Yuan Wang, Huadong Xu, Li Zhou, Lianghong Zheng, Changhe Wang, Zhuan Zhou
Neuropeptides released from dorsal root ganglion (DRG) neurons play essential roles in the neurotransmission of sensory inputs, including those underlying nociception and pathological pain. Neuropeptides are released from intracellular vesicles through two modes: a partial release mode called "kiss-and-run" (KAR) and a full release mode called "full fusion-like" (FFL). Using total internal reflection fluorescence (TIRF) microscopy, we traced the release of pH-sensitive green fluorescent protein-tagged neuropeptide Y (pHluorin-NPY) from individual dense-core vesicles in the soma and axon of single DRG neurons after Ca(2+) influx through either voltage-gated Ca(2+) channels (VGCCs) or ligand-gated transient receptor potential vanilloid 1 (TRPV1) channels...
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28633971/manganese-enhanced-magnetic-resonance-imaging-depicts-brain-activity-in-models-of-acute-and-chronic-pain-a-new-window-to-study-experimental-spontaneous-pain
#9
I M Devonshire, J J Burston, L Xu, A Lillywhite, M J Prior, D J G Watson, C M Greenspon, S J Iwabuchi, D P Auer, V Chapman
Application of functional imaging techniques to animal models is vital to understand pain mechanisms, but is often confounded by the need to limit movement artefacts with anaesthesia, and a focus on evoked responses rather than clinically relevant spontaneous pain and related hyperalgesia. The aim of the present study was to investigate the potential of manganese-enhanced magnetic resonance imaging (MEMRI) to measure neural responses during on-going pain that underpins hyperalgesia in pre-clinical models of nociception...
June 17, 2017: NeuroImage
https://www.readbyqxmd.com/read/28633926/synergic-stimulation-of-serotonin-5-ht1a-receptor-and-%C3%AE-2-adrenoceptors-for-neuropathic-pain-relief-preclinical-effects-of-2-substituted-imidazoline-derivatives
#10
Lorenzo Di Cesare Mannelli, Carla Ghelardini, Laura Micheli, Fabio Del Bello, Mario Giannella, Alessandro Piergentili, Wilma Quaglia
Neuropathic pain affects millions of people causing disability and impairing quality of life. Commonly used analgesics are generally characterized by limited therapeutic outcomes. The serotonin 5-HT1A receptor and the α2 adrenergic receptors are involved in central nociceptive mechanisms with a pivotal role in the inhibitory descending pain pathway. Since their stimulation may modulate the nervous signaling altered by neuropathies, the purpose of the present research is the study of the combined activation of 5-HT1A and α2 receptors by rationally designed imidazoline ligands ((S)-1 and 2-5) in a rat model of neuropathic pain (chronic constriction injury - CCI)...
June 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28628285/-fibromyalgia-state-of-the-issue-in-2017
#11
REVIEW
A Neuprez, J-M Crielaard
Fibromyalgia (FM), whose diagnostic criteria were originally established in 1990 and updated in 2010, consists of a syndrome characterized by the presence of deep and diffuse musculoskeletal pain associated with other subjective manifestations (sleep, mood, cognitive problems). The prevalence is assessed in the general population at 2.2 %. Various risk factors were identified: age, gender, level of education and socio-economic status. Various etiological hypotheses have been explored, whether in neuroimaging or from the point of view of possible neuroendocrine and cytokine perturbations...
June 2017: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28628232/sensory-mapping-of-pelvic-dermatomes-in-women-with-interstitial-cystitis-bladder-pain-syndrome
#12
Tatiana Sanses, Patrick McCabe, Ling Zhong, Aisha Taylor, Gisela Chelimsky, Sangeeta Mahajan, Tony Buffington, Adonis Hijaz, Sarah Ialacci, Jeffrey Janata, Thomas Chelimsky
AIM: To describe a sensory map of pelvic dermatomes in women with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). We hypothesized that if IC/BPS involves changes in central processing, then women with IC/BPS will exhibit sensory abnormalities in neurologic pelvic dermatomes. METHODS: Women with IC/BPS and healthy controls underwent neurologic examination that included evaluation of sharp pain sensitivity and vibration in dermatomes T12, L1, L2, S1-5. Peripheral nervous system sensitivity to pressure, vibration, and pinprick were scored using numeric rating scales (NRS)...
June 19, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28627793/increased-sympathetic-outflow-induces-adaptation-to-acute-experimental-pain
#13
Lior Dayan, Uri Hochberg, Hadas Nahman-Averbuch, Silviu Brill, Jacob N Ablin, Giris Jacob
BACKGROUND: There are interrelationships between the autonomic nervous system and pain. This study aims to explore the effect of different autonomic manipulations on pain perception and modulation. METHODS: Twenty healthy subjects (10 men and 10 women, mean age 25±3) participate in this single-blinded, semi-randomized, controlled study, which included 2 study visits. Warm and heat pain thresholds, conditioned pain modulation and pain adaptation were tested before and after administration of phenylephrine, clonidine, yohimbine and saline...
June 19, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28627589/effect-of-the-spinal-apelin%C3%A2-apj-system-on-the-pathogenesis-of-chronic-constriction-injury%C3%A2-induced-neuropathic-pain-in-rats
#14
Qingming Xiong, Wanyou He, Hanbing Wang, Jun Zhou, Yajun Zhang, Jian He, Chengxiang Yang, Bin Zhang
Apelin is hypothesized to serve a dual function in pain processing. Spinal administration of apelin induces hyperalgesia, while opioid receptors are implicated in the antinociceptive effects of apelin in acute nociceptive models. However, whether the apelin‑apelin receptor (APJ) system is involved in neuropathic pain remains to be elucidated. The present study aimed to evaluate the impact and mechanism of the spinal apelin‑APJ system in neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve produced sustained spinal apelin and APJ upregulation, which was associated with mechanical allodynia and heat hyperalgesia development in the hind‑paw plantar surface...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626482/the-possible-mechanisms-of-analgesia-produced-by-microinjection-of-morphine-into-the-lateral-habenula-in-the-acute-model-of-trigeminal-pain-in-rats
#15
Emad Khalilzadeh, Gholamreza Vafaei Saiah
This study aimed to assess the effect of intra-habenular injection of morphine on acute trigeminal pain in rats. Also here, we examined the involvement of raphe nucleus opioid and 5HT3 receptors on the antinociceptive activity of intra habenular morphine to explore the possibility of existence of descending antinociceptive relay between the habenula and raphe nucleus. The numbers of eye wiping response elicited by applying a drop (40 μL) of NaCl (5 M) solution on the corneal surface were taken as an index of acute trigeminal nociception...
June 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28625489/diosmin-reduces-chronic-constriction-injury-induced-neuropathic-pain-in-mice
#16
Mariana M Bertozzi, Ana C Rossaneis, Victor Fattori, Daniela T Longhi-Balbinot, Andressa Freitas, Fernando Q Cunha, José C Alves-Filho, Thiago M Cunha, Rubia Casagrande, Waldiceu A Verri
Injury or dysfunction of somatosensory system induces a complex syndrome called neuropathic pain, which still needs adequate pharmacological control. The current pharmacological treatments were in part developed from natural compounds. Flavonoids are natural polyphenolic molecules presenting varied biological activities and low toxicity. The flavonoid diosmin is a safe compound with good tolerability and low toxicity. This study evaluated the antinociceptive effect of diosmin in the sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain model...
June 15, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28624955/presynaptic-inhibition-of-nociceptive-neurotransmission-by-somatosensory-neuron-secreted-suppressors
#17
REVIEW
Kaicheng Li, Bing Cai, Changlin Li, Xu Zhang
Noxious stimuli cause pain by activating cutaneous nociceptors. The Aδ- and C-fibers of dorsal root ganglion (DRG) neurons convey the nociceptive signals to the laminae I-II of spinal cord. In the dorsal horn of spinal cord, the excitatory afferent synaptic transmission is regulated by the inhibitory neurotransmitter γ-aminobutyric acid and modulators such as opioid peptides released from the spinal interneurons, and by serotonin, norepinepherine and dopamine from the descending inhibitory system. In contrast to the accumulated evidence for these central inhibitors and their neural circuits in the dorsal spinal cord, the knowledge about the endogenous suppressive mechanisms in nociceptive DRG neurons remains very limited...
June 15, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28623618/endothelin-1-decreases-excitability-of-the-dorsal-root-ganglion-neurons-via-etb-receptor
#18
Nandkishor K Mule, Jitendra N Singh, Kunal U Shah, Anil Gulati, Shyam S Sharma
Endothelin-1 (ET-1) has been demonstrated to be a pro-nociceptive as well as an anti-nociceptive agent. However, underlying molecular mechanisms for these pain modulatory actions remain unclear. In the present study, we evaluated the ability of ET-1 to alter the nociceptor excitability using a patch clamp technique in acutely dissociated rat dorsal root ganglion (DRG) neurons. ET-1 produced an increase in threshold current to evoke an action potential (I threshold) and hyperpolarization of resting membrane potential (RMP) indicating decreased excitability of DRG neurons...
June 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28622486/the-physiological-basis-of-cervical-facet-mediated-persistent-pain-basic-science-and-clinical-challenges
#19
Meagan E Ita, Sijia Zhang, Timothy P Holsgrove, Sonia Kartha, Beth A Winkelstein
Synopsis Chronic neck pain is common and a primary clinical symptom of whiplash and other spinal injuries. Loading-induced neck injuries produce abnormal kinematics between the vertebrae, with the potential to injure facet joints and the afferent fibers that innervate the specific joint tissues, including the capsular ligament. Mechanoreceptive and nociceptive afferents that innervate the facet have their peripheral terminals in the capsule, cell bodies in the dorsal root ganglia, and terminal processes in the spinal cord...
June 16, 2017: Journal of Orthopaedic and Sports Physical Therapy
https://www.readbyqxmd.com/read/28622274/a-role-for-neurokinin-1-receptor-neurons-in-the-rostral-ventromedial-medulla-in-the-development-of-chronic-postthoracotomy-pain
#20
Sergey G Khasabov, Jeffrey Chi-Fei Wang, Donald A Simone, Gary R Strichartz
Thoracotomy results in chronic postoperative 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...
July 2017: Pain
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