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https://www.readbyqxmd.com/read/28732166/mel-n16-a-series-of-novel-endomorphin-analogs-with-good-analgesic-activity-and-a-favorable-side-effect-profile
#1
Xin Liu, Long Zhao, Yuan Wang, Jingjing Zhou, Dan Wang, Yixin Zhang, Xianghui Zhang, Zhaojuan Wang, Dongxu Yang, Lingyun Mou, Rui Wang
Opioid peptides are neuromodulators that bind to opioid receptors and reduce pain sensitivity. Endomorphins are one of the most active endogenous opioid peptides, and they have good affinity and selectivity toward the μ opioid receptor. However, their clinical usage is hindered by their inability to cross the blood-brain barrier, and their poor in vivo activity after peripheral injection. In order to overcome these defects, we have designed and synthesized a series of novel endomorphin analogs with multiple site modifications...
July 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28731982/peripheral-oxytocin-receptors-inhibit-the-nociceptive-input-signal-to-spinal-dorsal-horn-wide-dynamic-range-neurons
#2
Abimael González-Hernández, Alfredo Manzano-García, Guadalupe Martínez-Lorenzana, Irma A Tello-García, Martha Carranza, Carlos Arámburo, Miguel Condés-Lara
Oxytocin has emerged as a mediator of endogenous analgesia in behavioral and electrophysiological experiments. In fact, oxytocin 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 oxytocin blocked the first sensorial activity Aδ- and C-fibers recorded in the spinal cord neurons...
July 19, 2017: Pain
https://www.readbyqxmd.com/read/28730837/molecular-basis-of-trpa1-regulation-in-nociceptive-neurons-a-review
#3
A Kádková, V Synytsya, J Krusek, L Zímová, V Vlachová
Transient receptor potential A1 (TRPA1) is an excitatory ion channel that functions as a cellular sensor, detecting a wide range of proalgesic agents such as environmental irritants and endogenous products of inflammation and oxidative stress. Topical application of TRPA1 agonists produces an acute nociceptive response through peripheral release of neuropeptides, purines and other transmitters from activated sensory nerve endings. This, in turn, further regulates TRPA1 activity downstream of G-protein and phospholipase C-coupled signaling cascades...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28730280/evidence-for-the-involvement-of-the-gabaergic-but-not-serotonergic-transmission-in-the-anxiolytic-like-effect-of-bisabolol-in-the-mouse-elevated-plus-maze
#4
Mohaddeseh Abouhosseini Tabari, Mohammad Amir Bagherpour Tehrani
Bisabolol (α-(-)-bisabolol) is a sesquiterpene which is a part of the essential oil of a variety of plants, but its common source is German chamomile. Several bioactivities including anti-inflammatory, anti-nociceptive, and anti-tumor effects were attributed to bisabolol. However, the neuropharmacological properties of bisabolol have not yet been reported. The present study evaluated behavioral effects of bisabolol using elevated plus maze (EPM), open field test (OFT), and rotarod test. Moreover, this study also examined whether the 5-HT1A and GABAA-benzodiazepine receptor systems are involved in the anxiolytic-like effects of bisabolol...
July 20, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28729062/pharmacological-activation-of-ampk-inhibits-incision-evoked-mechanical-hypersensitivity-and-the-development-of-hyperalgesic-priming-in-mice
#5
Michael D Burton, Dipti V Tillu, Khadijah Mazhar, Galo L Mejia, Marina N Asiedu, Kufreobong Inyang, Travis Hughes, Bo Lian, Gregory Dussor, Theodore J Price
New therapeutics to manage post-surgical pain are needed to mitigate the liabilities of opioid and other analgesics. Our previous work shows that key modulators of excitability in peripheral nociceptors, such as extracellular signal-regulated kinases (ERK) are inhibited by activation of adenosine monophosphate activated protein kinase (AMPK). We hypothesized that AMPK activation would attenuate acute incision-evoked mechanical hypersensitivity and the development of hyperalgesic priming caused by surgery in mice...
July 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28727698/high-prevalence-of-neuropathic-pain-component-in-patients-with-low-back-pain-evidence-from-meta-analysis
#6
Kapil Gudala, Dipika Bansal, Rambabu Vatte, Babita Ghai, Fabrizio Schifano, Chandrasehkar Boya
BACKGROUND: Low back pain (LBP) is a complex syndrome which includes a nociceptive (NcP) component, a neuropathic (NeP) component, or a mixture of components (mixed pain). The NeP component (NePC) in LBP is defined as the presence of NeP with or without an NcP. OBJECTIVE: This meta-analysis aimed at assessing the pooled prevalence of NePC in patients with LBP and at identifying the factors causing significant heterogeneity in reported prevalence. STUDY DESIGN: Meta-analysis...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28726995/effects-of-transdermal-flunixin-meglumine-on-pain-biomarkers-at-dehorning-in-calves
#7
M D Kleinhenz, N K Van Engen, P J Gorden, J Ji, P Walsh, J F Coetzee
The objective of this study was to evaluate the analgesic properties of transdermal flunixin meglumine when given at the time of dehorning on pain biomarkers. Twenty-four weaned male Holstein calves, 6 to 8 wk of age were enrolled into the study. The calves were randomly assigned to 1 of 3 treatment groups: 1) transdermal flunixin and dehorn (DH-FLU); 2) transdermal flunixin and sham dehorn (SHAM-FLU); and 3) placebo and dehorn (DH-PLBO). Transdermal flunixin at a label dose of 3.33 mg/kg (or placebo at an equivalent volume) was administered as a pour-on along the top-line of the calves in each treatment group concurrently with electrocautery dehorning or sham dehorning...
May 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28726567/possible-mechanisms-involved-in-the-anti-nociceptive-effects-of-hydro-ethanolic-leaf-extract-of-ziziphus-abyssinica
#8
Eric Boakye-Gyasi, Isaac Tabiri Henneh, Wonder Kofi Mensah Abotsi, Elvis Ofori Ameyaw, Eric Woode
CONTEXT: Various parts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) have been used in Ghanaian and African traditional medicine as an analgesic. However, there are little scientific data to support the anti-nociceptive effects of the hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) as well as the possible mechanisms involved in its anti-nociceptive effects. PURPOSE: To predict possible nociceptive pathways involved in the anti-nociceptive effects of EthE...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28725185/reticular-formation-and-pain-the-past-and-the-future
#9
REVIEW
Isabel Martins, Isaura Tavares
The involvement of the reticular formation (RF) in the transmission and modulation of nociceptive information has been extensively studied. The brainstem RF contains several areas which are targeted by spinal cord afferents conveying nociceptive input. The arrival of nociceptive input to the RF may trigger alert reactions which generate a protective/defense reaction to pain. RF neurons located at the medulla oblongata and targeted by ascending nociceptive information are also involved in the control of vital functions that can be affected by pain, namely cardiovascular control...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28724992/opposite-bidirectional-shifts-in-excitation-and-inhibition-in-specific-types-of-dorsal-horn-interneurons-are-associated-with-spasticity-and-pain-post-sci
#10
Olga Kopach, Volodymyr Medvediev, Volodymyr Krotov, Anya Borisyuk, Vitaliy Tsymbaliuk, Nana Voitenko
Spasticity, a common complication after spinal cord injury (SCI), is frequently accompanied by chronic pain. The physiological origin of this pain (critical to its treatment) remains unknown, although spastic motor dysfunction has been related to the hyperexcitability of motoneurons and to changes in spinal sensory processing. Here we show that the pain mechanism involves changes in sensory circuits of the dorsal horn (DH) where nociceptive inputs integrate for pain processing. Spasticity is associated with the DH hyperexcitability resulting from an increase in excitation and disinhibition occurring in two respective types of sensory interneurons...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724917/endocannabinoids-have-opposing-effects-on-behavioral-responses-to-nociceptive-and-non-nociceptive-stimuli
#11
Torrie Summers, Brandon Hanten, Warren Peterson, Brian Burrell
The endocannabinoid system is thought to modulate nociceptive signaling making it a potential therapeutic target for treating pain. However, there is evidence that endocannabinoids have both pro- and anti-nociceptive effects. In previous studies using Hirudo verbana (the medicinal leech), endocannabinoids were found to depress nociceptive synapses, but enhance non-nociceptive synapses. Here we examined whether endocannabinoids have similar bidirectional effects on behavioral responses to nociceptive vs. non-nociceptive stimuli in vivo...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724356/a-one-year-follow-up-study-of-chronic-pain-in-community-dwelling-older-adults-with-and-without-neuropathic-pain
#12
Susanna Rapo-Pylkkö, Maija Haanpää, Helena Liira
BACKGROUND: Chronic, mostly musculoskeletal pain is common among older adults. Little is known about the prognosis of chronic pain and the neuropathic pain qualities in older adults. We studied a cohort of community-dwelling older adults, clinically assessed their pain states, classified their type of pain (nociceptive, neuropathic or combined) and followed them up for a year. METHODS: At baseline, a geriatrician clinically examined all study patients and classified their type of pain in collaboration with a pain specialist...
July 19, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28724217/chondroprotective-and-anti-nociceptive-effects-of-caffeoylquinic-acid-in-osteoarthritis-by-downregulating-catabolic-activity-and-oxidative-damage-in-chondrocytes
#13
Luping Liu, Yongmei Li
We evaluated the chondroprotective and anti-nociceptive effects of caffeoylquinic acid (CA) in a rat osteoarthritis (OA) model. Monosodium iodoacetate was injected intra-articularly in the rats to produce OA. The rats were divided into three groups: control, OA group, which received vehicle, and the CA-treated group, which received CA (50mg/kg, p.o.) for 14days. At the end of the protocol, pain was estimated by observing the paw withdrawal threshold and latency. Degeneration of cartilage was assessed through histomorphological and microscopical examination of joints...
July 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28722694/early-life-vincristine-exposure-evokes-mechanical-pain-hypersensitivity-in-the-developing-rat
#14
Katie A Schappacher, Lauren Styczynski, Mark L Baccei
Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat...
May 30, 2017: Pain
https://www.readbyqxmd.com/read/28722336/evidence-for-the-modulation-of-nociception-in-mice-by-central-mast-cells
#15
C L Kissel, K J Kovács, A A Larson
BACKGROUND: Hyperalgesia that develops following nerve ligation corresponds temporally and in magnitude with the number of thalamic mast cells located contralateral to the ligature. We tested the possibility that mast cells modulate nociception centrally, similar to their role in the periphery. METHODS: We examined the central effect of two hyperalgesic compounds that induce mast cell degranulation and of stabilized mast cells using cromolyn. RESULTS: Thermal hyperalgesia (tail flick) induced by nerve growth factor (NGF, a neurotrophic compound) and mechanical hyperalgesia (von Frey) induced by dynorphin A (1-17) (opioid compound) each correlated with the per cent of thalamic mast cells that were degranulated...
July 19, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28722281/collagen-organization-regulates-stretch-initiated-pain-related-neuronal-signals-in-vitro-implications-for-structure-function-relationships-in-innervated-ligaments
#16
Sijia Zhang, Sagar Singh, Beth A Winkelstein
Injury to the spinal facet capsule, an innervated ligament with heterogeneous collagen organization, produces pain. Although mechanical facet joint trauma activates embedded afferents, it is unclear if, and how, the varied extracellular microstructure of its ligament affects sensory transduction for pain from mechanical inputs. To investigate the effects of macroscopic deformations on afferents in collagen matrices with different organizations, an in vitro neuron-collagen construct (NCC) model was used. NCCs with either randomly organized or parallel aligned collagen fibers were used to mimic the varied microstructure in the facet capsular ligament...
July 19, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28722116/opioids-for-cancer-related-pain-in-children-and-adolescents
#17
REVIEW
Philip J Wiffen, Tess E Cooper, Anna-Karenia Anderson, Andrew L Gray, Marie-Claude Grégoire, Gustaf Ljungman, Boris Zernikow
BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. Views on children's pain have changed over time and relief of pain is now seen as important. In the past, pain was largely dismissed and was frequently left untreated, and it was assumed that children quickly forgot about painful experiences...
July 19, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28722015/trpv1-regulates-excitatory-innervation-of-olm-neurons-in-the-hippocampus
#18
Joaquin I Hurtado-Zavala, Binu Ramachandran, Saheeb Ahmed, Rashi Halder, Christiane Bolleyer, Ankit Awasthi, Markus A Stahlberg, Robin J Wagener, Kristin Anderson, Ryan M Drenan, Henry A Lester, Julie M Miwa, Jochen F Staiger, Andre Fischer, Camin Dean
TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro...
July 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28720830/effect-of-cxcl12-cxcr4-signaling-on-neuropathic-pain-after-chronic-compression-of-dorsal-root-ganglion
#19
Yang Yu, Xini Huang, Yuwei Di, Lintao Qu, Ni Fan
Neuropathic pain is a complex, chronic pain state that often accompanies tissue damage, inflammation or injury of the nervous system. However the underlying molecular mechanisms still remain unclear. Here, we showed that CXCL12 and CXCR4 were upregulated in the dorsal root ganglion (DRG) after chronic compression of DRG (CCD), and some CXCR4 immunopositive neurons were also immunopositive for the nociceptive neuronal markers IB4, TRPV1, CGRP, and substance P. The incidence and amplitude of CXCL12-induced Ca(2+) response in primary sensory neurons from CCD mice was significantly increased compared to those from control animals...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720713/sensory-processing-of-deep-tissue-nociception-in-the-rat-spinal-cord-and-thalamic-ventrobasal-complex
#20
Shafaq Sikandar, Steven J West, Stephen B McMahon, David L Bennett, Anthony H Dickenson
Sensory processing of deep somatic tissue constitutes an important component of the nociceptive system, yet associated central processing pathways remain poorly understood. Here, we provide a novel electrophysiological characterization and immunohistochemical analysis of neural activation in the lateral spinal nucleus (LSN). These neurons show evoked activity to deep, but not cutaneous, stimulation. The evoked responses of neurons in the LSN can be sensitized to somatosensory stimulation following intramuscular hypertonic saline, an acute model of muscle pain, suggesting this is an important spinal relay site for the processing of deep tissue nociceptive inputs...
July 2017: Physiological Reports
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