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Sheng-Ren Chen, Yi-Yu Ke, Teng-Kuang Yeh, Shu-Yu Lin, Li-Chin Ou, Shu-Chun Chen, Wan-Ting Chang, Hsiao-Fu Chang, Zih-Huei Wu, Chih-Chien Hsieh, Ping-Yee Law, Horace H Loh, Chuan Shih, Yiu-Kay Lai, Shiu-Hwa Yeh, Shau-Hua Ueng
μ-Opioid receptor (MOR) agonists are analgesics used clinically for the treatment of moderate to severe pain, but their use is associated with severe adverse effects such as respiratory depression, constipation, tolerance, dependence, and rewarding effects. In this study, we identified N-({2-[(4-bromo-2-trifluoromethoxyphenyl)sulfonyl]-1,2,3,4-tetrahydro-1-isoquinolinyl}methyl)cyclohexanecarboxamide (1) as a novel opioid receptor agonist by high-throughput screening. Structural modifications made to 1 to improve potency and blood-brain-barrier (BBB) penetration resulted in compounds 45 and 46...
September 20, 2016: European Journal of Medicinal Chemistry
Christine Petschow, Lukas Scheef, Sebastian Paus, Nadine Zimmermann, Hans H Schild, Thomas Klockgether, Henning Boecker
BACKGROUND & OBJECTIVE: Pain is a common non-motor symptom in Parkinson's disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson's disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. METHODS: 13 right-handed early-stage Parkinson's disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects...
2016: PloS One
Shanta Islam, Md Shafiullah Shajib, Tajnin Ahmed
BACKGROUND: Celosia cristata Linn. (Amaranthaceae) is used in traditional medicine for the treatment of headache, sores, ulcers, eye inflammations, skin eruption, painful menstruation and carpal tunnel syndrome. This study was performed to evaluate the antinociceptive activity of methanol extract of the whole plant of C. cristata (MECC). METHODS: The evaluation of the antinociceptive effect of MECC was performed using thermal (hot plate, tail immersion test) and chemical (acetic acid, formalin, and glutamate-induced nociception test) pain models in mice at four different doses (50, 100, 200, 400 mg/kg; p...
October 22, 2016: BMC Complementary and Alternative Medicine
Tatsuya Isomura, Masahiko Sumitani, Ko Matsudaira, Mika Kawaguchi, Reo Inoue, Jun Hozumi, Takeyuki Tanaka, Hirofumi Oshima, Kanto Mori, Shuji Taketomi, Hiroshi Inui, Keitaro Tahara, Ryota Yamagami, Kazuhiro Hayakawa
OBJECTIVE: We aimed to assess the diagnostic utility of the linguistically validated Japanese version of the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS-J) as a screening tool for neuropathic pain in the clinical setting. METHODS: Patients with neuropathic pain or nociceptive pain who were 20 to 85 years of age were included. Sensitivity and specificity using the original cutoff value of 12 were assessed to evaluate the diagnostic utility of the LANSS-J...
October 22, 2016: Pain Practice: the Official Journal of World Institute of Pain
Daniel Lordelo San Martin, Dislene Nascimento Dos Santos, Abrahão Fontes Baptista
OBJECTIVE: To describe the pain in patients infected with human T-cell lymphotropic virus type 1, clinically and epidemiologically. METHODS: This systematic review was based on The PRISMA Statement. Four reviewers searched PUBMED, SciELO, LILACS and BIREME for data from observational studies and clinical trials (n≥30) regarding pain prevalence, characteristics, and associated factors in patients with human T-cell lymphotropic virus type 1. No limits on publication date or language were established...
October 18, 2016: Brazilian Journal of Infectious Diseases
Wei Tuo, Natascha Leleu-Chavain, John Spencer, Supojjanee Sansook, Regis Millet, Philippe Chavatte
Fatty acid ethanolamides (FAEs) and endocannabinoids (ECs) have been shown to alleviate pain and inflammation, regulate motility and appetite, and produce anti-cancer, anxiolytic, and neuroprotective efficacies via cannabinoid receptor type 1 (CB1) or type 2 (CB2), or via peroxisome proliferator-activated receptor α (PPAR-α) stimulation. FAEs and ECs are synthesized by a series of endogenous enzymes, including N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), or phospholipase C (PLC), and their metabolism is mediated by several metabolic enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamine acid amidase (NAAA), or cyclooxygenase-2 (COX-2)...
October 21, 2016: Journal of Medicinal Chemistry
W Xia, C D Mørch, D Matre, O K Andersen
BACKGROUND: This study aimed to explore conditioned pain modulation (CPM) effect on long-term potentiation (LTP)-like pain amplification induced by cutaneous 10-Hz conditioning electrical stimulation (CES). METHODS: Conditioned pain modulation was induced by cold pressor conditioning stimulus (CPCS) (4 °C) which was applied immediately before CES in the active session. In the control session, water with a temperature of 32 °C was used. Twenty subjects participated in two sessions in a randomized crossover design with at least 1-week interval...
October 20, 2016: European Journal of Pain: EJP
Umberto Melia, Eva Gabarron, Mercé Agustí, Nuria Souto, Patricia Pineda, Joan Fontanet, Montserrat Vallverdu, Erik Weber Jensen, Pedro Gambus
The objective of this work is to compare the performances of two electroencephalogram based indices for detecting loss of consciousness and loss of response to nociceptive stimulation. Specifically, their behaviour after drug induction and during recovery of consciousness was pointed out. Data was recorded from 140 patients scheduled for general anaesthesia with a combination of propofol and remifentanil. The qCON 2000 monitor (Quantium Medical, Barcelona, Spain) was used to calculate the qCON and qNOX. Loss of response to verbal command and loss of eye-lash reflex were assessed during the transition from awake to anesthetized, defining the state of loss of consciousness...
October 20, 2016: Journal of Clinical Monitoring and Computing
Szczepan Mogilski, Monika Kubacka, Dorota Łażewska, Małgorzata Więcek, Monika Głuch-Lutwin, Małgorzata Tyszka-Czochara, Karolina Bukowska-Strakova, Barbara Filipek, Katarzyna Kieć-Kononowicz
OBJECTIVE AND DESIGN: Histamine H4 receptor (H4R) offers a great potential for new therapeutic strategies for the treatment of inflammation-based diseases. The aim of this study is to present the pharmacological profile of two recently synthesized ligands of H4R with particular reference to their anti-inflammatory and analgesic activity. MATERIALS AND SUBJECTS: We used mice and rats in the in vivo tests. We also used murine RAW 264.7 cells and isolated guinea-pig ileum in in vitro test...
October 20, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Jinping Shao, Jing Cao, Jiannan Wang, Xiuhua Ren, Songxue Su, Ming Li, Zhihua Li, Qingzan Zhao, Weidong Zang
Voltage-gated sodium channels, which are involved in pain pathways, have emerged as major targets for therapeutic intervention in pain disorders. Nav1.7, the tetrodotoxin-sensitive voltage-gated sodium channel isoform encoded by SCN9A and predominantly expressed in pain-sensing neurons in the dorsal root ganglion, plays a crucial role in nociception. MicroRNAs are highly conserved, small non-coding RNAs. Through binding to the 3' untranslated region of their target mRNAs, microRNAs induce the cleavage and/or inhibition of protein translation...
2016: Molecular Pain
Shehla Akbar, Fazal Subhan, Nasiara Karim, Muhammad Shahid, Nisar Ahmad, Gowhar Ali, Wajahat Mahmood, Khwaja Fawad
BACKGROUND: Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities. OBJECTIVE: Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABAA receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ana María Jiménez-García, Leandro Ruíz-Leyva, Cruz Miguel Cendán, Carmen Torres, Mauricio R Papini, Ignacio Morón
Reduced sensitivity to physical pain (hypoalgesia) has been reported after events involving reward devaluation. Reward devaluation was implemented in a consummatory successive negative contrast (cSNC) task. Food-deprived Wistar rats had access to 32% sucrose during 16 sessions followed by access to 4% sucrose during 3 additional sessions. An unshifted control group had access to 4% sucrose throughout the 19 sessions. Pain sensitivity was measured using von Frey filaments (Experiment 1) and Hargreaves thermal stimuli (Experiment 2) in pretraining baseline, 5 min, and 300 min after either the first (session 17) or second (session 18) devaluation session in the cSNC situation...
2016: PloS One
Andrea Bowyer, Colin F Royse
PURPOSE OF REVIEW: Recovery after surgery is a complex interplay of the patient, the surgery, and the perioperative anaesthesia management. Assessment of recovery should address the needs of multiple stakeholders, including the institutions and healthcare providers, but primarily should be focused on the patients and their perception of quality of recovery and return to normalcy. This review will summarize the development of assessment of recovery to a multidimensional dichotomous construct that requires a real-time assessment tool validated for repeat measures and containing cognitive assessment...
October 18, 2016: Current Opinion in Anaesthesiology
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Diego Dal Ben, Anna Marchenkova, Ajiroghene Thomas, Catia Lambertucci, Andrea Spinaci, Gabriella Marucci, Andrea Nistri, Rosaria Volpini
Blocking membrane currents evoked by the activation of purinergic P2X3 receptors localized on nociceptive neurons represents a promising strategy for the development of agents useful for the treatment of chronic pain conditions. Among compounds endowed with such antagonistic action, 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) is an ATP analogue, whose inhibitory activity on P2X receptors has been previously reported. Based on the results of molecular modelling studies performed with homology models of the P2X3 receptor, novel adenosine nucleotide analogues bearing cycloalkyl or arylalkyl substituents replacing the trinitrophenyl moiety of TNP-ATP were designed and synthesized...
October 18, 2016: Purinergic Signalling
Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Ranjana Bhandari, Anurag Kuhad
Neuropathic pain is a debilitating disease which affects central as well as peripheral nervous system. Transient receptor potential (TRP) channels are ligand-gated ion channels that detect physical and chemical stimuli and promote painful sensations via nociceptor activation. TRP channels have physiological role in the mechanisms controlling several physiological responses like temperature and mechanical sensations, response to painful stimuli, taste, and pheromones. TRP channel family involves six different TRPs (TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPA1) which are expressed in pain sensing neurons and primary afferent nociceptors...
October 18, 2016: Inflammopharmacology
Petra Mrozkova, Diana Spicarova, Jiri Palecek
Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors in the peripheral nerve endings are implicated in the development of increased sensitivity to mechanical and thermal stimuli, especially during inflammatory states. Both PAR2 and TRPV1 receptors are co-expressed in nociceptive dorsal root ganglion (DRG) neurons on their peripheral endings and also on presynaptic endings in the spinal cord dorsal horn. However, the modulation of nociceptive synaptic transmission in the superficial dorsal horn after activation of PAR2 and their functional coupling with TRPV1 is not clear...
2016: PloS One
Neil C Ford, Mark L Baccei
Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e. 'leak') ion channels expressed by these distinct populations during early life...
October 14, 2016: Neuroscience
Nikele Nadur-Andrade, Camila Squarzoni Dale, Victoria Regina da Silva Oliveira, Elaine Flamia Toniolo, Regiane Dos Santos Feliciano, José Antonio da Silva, Stella Regina Zamuner
BACKGROUND: Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv), as well as the mechanisms involved was investigated. METHODOLOGY/PRINCIPAL FINDINGS: Bmv (1 μg) was injected through the intraplantar route in the right hind paw of mice...
October 2016: PLoS Neglected Tropical Diseases
Junjie Luo, Wei L Shen, Craig Montell
Avoidance of noxious ambient heat is crucial for survival. A well-known phenomenon is that animals are sensitive to the rate of temperature change. However, the cellular and molecular underpinnings through which animals sense and respond much more vigorously to fast temperature changes are unknown. Using Drosophila larvae, we found that nociceptive rolling behavior was triggered at lower temperatures and at higher frequencies when the temperature increased rapidly. We identified neurons in the brain that were sensitive to the speed of the temperature increase rather than just to the absolute temperature...
October 17, 2016: Nature Neuroscience
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