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endogenous analgesia

D Reiss, R A Ceredig, T Secher, J Boué, F Barreau, G Dietrich, C Gavériaux-Ruff
BACKGROUND: Opiates act through opioid receptors to diminish pain. Here, we investigated whether mu (MOR) and delta (DOR) receptor endogenous activity assessed in the whole mouse body or in particular at peripheral receptors on primary nociceptive neurons, control colonic pain. METHODS: We compared global MOR and DOR receptor knockout (KO) mice, mice with a conditional deletion of MOR and DOR in Nav1.8-positive nociceptive primary afferent neurons (cKO), and control floxed mice of both genders for visceral sensitivity...
October 17, 2016: European Journal of Pain: EJP
Jun-Ying Du, Yi Liang, Jun-Fan Fang, Yong-Liang Jiang, Xiao-Mei Shao, Xiao-Fen He, Jian-Qiao Fang
Exogenous and endogenous opioids have been shown to modulate the immune system. Morphine-induced immunosuppression has been investigated extensively. However, the immune-regulating function of endogenous opioid peptides is unclear. The present study aimed to evaluate the difference in effects on cellular immune function between recombinant rat β-endorphin (β-EP; 50 µg/kg) and plant source morphine (10 mg/kg) via intraperitoneal injection treatment in a rat model of bone cancer pain. Walker 256 cells were injected into a tibial cavity injection to establish the bone cancer pain model...
October 2016: Experimental and Therapeutic Medicine
Amandine Dupuis, Anne-Sophie Wattiez, Jérémy Pinguet, Damien Richard, Frédéric Libert, Maryse Chalus, Youssef Aissouni, Benoit Sion, Denis Ardid, Philippe Marin, Alain Eschalier, Christine Courteix
Antidepressants are one of the first line treatments for neuropathic pain but their use is limited by the incidence and severity of side effects of tricyclics and the weak effectiveness of selective serotonin reuptake inhibitors (SSRIs). Serotonin type 2A (5-HT2A) receptors interact with PDZ proteins that regulate their functionality and SSRI efficacy to alleviate pain. We investigated whether an interfering peptide (TAT-2ASCV) disrupting the interaction between 5-HT2A receptors and associated PDZ proteins would improve the treatment of traumatic neuropathic allodynia...
September 20, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Greg Dussor, Yu-Qing Cao
Migraine is among the most common diseases on earth and one of the most disabling, the latter due in large part to poor treatment efficacy. Development of new therapeutics is dependent on the identification of mechanisms contributing to migraine and discovery of targets for new drugs. Numerous genome-wide association studies (GWAS) have implicated the transient receptor-potential M8 (TRPM8) channel in migraine. This channel is predominantly expressed on peripheral sensory neurons and is known as the sensor for cold temperature in cutaneous tissue but is also expressed on deep visceral afferents where cold is not likely a stimulus...
October 2016: Headache
Nathalie Wrobel, Tahmine Fadai, Stefanie Brassen, Ulrike Bingel
: The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanisms responsible for the development of chronic pain overlap with mechanisms involved in aging, potentially implicating age-related changes in descending modulatory pathways. This observation raises the question whether other forms of endogenous pain modulation, in particular placebo analgesia, become compromised with age. Given the known contribution of placebo effects to analgesic treatment outcomes this question is of important clinical relevance...
September 8, 2016: Journal of Pain: Official Journal of the American Pain Society
Dominika Labuz, Melih Ö Celik, Andreas Zimmer, Halina Machelska
Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively...
2016: Scientific Reports
Philippe Sitbon, Alain Van Elstraete, Leila Hamdi, Victor Juarez-Perez, Jean-Xavier Mazoit, Dan Benhamou, Catherine Rougeot
BACKGROUND: Opiorphin is a naturally occurring potent analgesic human peptide. It protects enkephalins from degradation and inhibits pain perception in various acute pain models via activation of endogenous opioid pathways. However, the efficacy of opiorphin continuous infusion and its chemically stable form, STR-324, in postoperative pain is unknown. METHODS: Using the Brennan model of plantar incision-induced hypersensitivity, the authors examined the postsurgical analgesic response to mechanical and thermal stimuli of 7-day continuously intravenously infused drugs (8 to 10 rats per group)...
November 2016: Anesthesiology
Susan Hua
Peripheral immune cell-mediated analgesia in inflammation is an important endogenous mechanism of pain control. Opioid receptors localized on peripheral sensory nerve terminals are activated by endogenous opioid peptides released from immune cells to produce significant analgesia. Following transendothelial migration of opioid-containing leukocytes into peripheral sites of inflammation, opioid peptides are released into a harsh milieu associated with an increase in temperature, low pH, and high proteolytic activity...
2016: Frontiers in Immunology
Haiqing Liu, Yanjun Tian, Bingyun Ji, Hai Lu, Qing Xin, Yunlu Jiang, Liangcai Ding, Jingmei Zhang, Jing Chen, Bo Bai
Together with its endogenous ligands (dynorphin), the kappa opioid receptor (KOR) plays an important role in modulating various physiological and pharmacological responses, with a classical G protein-coupled pathway mediating analgesia and non-G protein-dependent pathway, especially the β-arrestin-dependent pathway, eliciting side effects of dysphoria, aversion, drug-seeking in addicts, or even relapse to addiction. Although mounting evidence has verified a functional overlap between dynorphin/KOR and neurotensin/neurotensin receptor 1 (NTSR1) systems, little is known about direct interaction between the two receptors...
August 12, 2016: Biochimica et Biophysica Acta
Renato Leonardo de Freitas, Priscila Medeiros, Asmat Ullah Khan, Norberto Cysne Coimbra
Generalised tonic and tonic-clonic seizures are followed by significant increase in nociceptive thresholds in both laboratory animals and humans. The endogenous opioid peptides play a role in antinociceptive signalling, and the periaqueductal grey matter (PAG) is recruited to induce analgesia. Thus, the aim of this investigation was to evaluate the role of µ1 -opioid receptors in the dorsomedial (dm) and ventrolateral (vl) columns of PAG in post-ictal antinociception. Pentylenetetrazole (PTZ; 64 mg/kg), which is an ionotropic GABA-mediated Cl(-) influx antagonist, was intraperitoneally (IP) administered to induce tonic-clonic seizures in Wistar rats...
December 2016: Synapse
Karin R Aubrey, Geoffrey M Drew, Hyo-Jin Jeong, Benjamin K Lau, Christopher W Vaughan
The midbrain periaqueductal grey (PAG) has a crucial role in coordinating endogenous analgesic responses to physiological and psychological stressors. Endocannabinoids are thought to mediate a form of stress-induced analgesia within the PAG by relieving GABAergic inhibition of output neurons, a process known as disinhibition. This disinhibition is thought to be achieved by a presynaptic reduction in GABA release probability. We examined whether other mechanisms have a role in endocannabinoid modulation of GABAergic synaptic transmission within the rat PAG...
July 27, 2016: Journal of Physiology
Linda Hermans, Patrick Calders, Jessica Van Oosterwijck, Ellen Verschelde, Eva Bertel, Mira Meeus
BACKGROUND: Offset analgesia (OA) is an increasingly described phenomenon to measure endogenous pain inhibition, in which a greater decrease in pain intensity is experienced than would be predicted by the decrease in painful stimulation. The temporal filtering in this OA phenomenon differs from the spatial filtering in the commonly described conditioned pain modulation (CPM). Yet, the knowledge on the efficacy of OA in chronic pain patients is scarce, compared to CPM efficacy. OBJECTIVE: This systematic review has been conducted to provide an overview of the current knowledge regarding OA, and to compare it to CPM...
July 2016: Pain Physician
Debo Qi, Shuqin Wu, Yuhua Zhang, Weimin Li
AIMS: To investigate the efficacy of electroacupuncture (EA) alleviation of acute visceral hyperalgesia, the frequency dependence of this efficacy, and the difference in endogenous opioid pathways as underlying mechanism explaining the frequency dependence. MAIN METHODS: A visceral hyperalgesia model was established by colorectal instillation of 2% acetic acid (AA) in adult rats. EA treatment at 2Hz, 100Hz, 2/100Hz and sham EA were performed at two bilateral acupoints, ST-36 and ST-37, in the hind-limbs...
September 1, 2016: Life Sciences
Doungkamol Alongkronrusmee, Terrance Chiang, Richard M van Rijn
Delta opioid receptors (DORs) are heavily involved in alcohol-mediated processes in the brain. In this chapter we provide an overview of studies investigating how alcohol directly impacts DOR pharmacology and of early studies indicating DOR modulation of alcohol behavior. We will offer a brief summary of the different animal species used in alcohol studies investigating DORs followed by a broader overview of the types of alcohol behaviors modulated by DORs. We will highlight a small set of studies investigating the relationship between alcohol and DORs in analgesia...
June 18, 2016: Handbook of Experimental Pharmacology
Dongyang Huang, Sha Huang, Haixia Gao, Yani Liu, Jinlong Qi, Pingping Chen, Caixue Wang, Jason L Scragg, Alexander Vakurov, Chris Peers, Xiaona Du, Hailin Zhang, Nikita Gamper
AIMS: Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. RESULTS: SP acutely inhibited T-type voltage-gated Ca(2+) channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS...
August 10, 2016: Antioxidants & Redox Signaling
Chunbo He, Junbin Gong, Lixia Yang, Hongwei Zhang, Shouliang Dong, Lanxia Zhou
The present study focused on the interactive pain regulation of endokinin A/B (EKA/B, the common C-terminal decapeptide in EKA and EKB) or endokinin C/D (EKC/D, the common C-terminal duodecapeptide in EKC and EKD) on chimeric peptide MCRT (YPFPFRTic-NH2, based on YPFP-NH2 and PFRTic-NH2) at the supraspinal level in mice. Results demonstrated that the co-injection of nanomolar EKA/B and MCRT showed moderate regulation, whereas 30 pmol EKA/B had no effect on MCRT. The combination of EKC/D and MCRT produced enhanced antinociception, which was nearly equal to the sum of the mathematical values of single EKC/D and MCRT...
September 2016: Canadian Journal of Physiology and Pharmacology
Mark F Bird, Maria Camilla Cerlesi, Mark Brown, Davide Malfacini, Vanessa Vezzi, Paola Molinari, Laura Micheli, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Remo Guerrini, Girolamo Calò, David G Lambert
INTRODUCTION: Opioid receptors are currently classified as Mu (μ), Delta (δ), Kappa (κ) plus the opioid related nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP). Despite compelling evidence for interactions and benefits of targeting more than one receptor type in producing analgesia, clinical ligands are Mu agonists. In this study we have designed a Mu-NOP agonist named DeNo. The Mu agonist component is provided by dermorphin, a peptide isolated from the skin of Phyllomedusa frogs and the NOP component by the endogenous agonist N/OFQ...
2016: PloS One
Lilian Basso, Jérôme Boué, Karim Mahiddine, Catherine Blanpied, Sébastien Robiou-du-Pont, Nathalie Vergnolle, Céline Deraison, Gilles Dietrich
BACKGROUND: T cell-derived opioids play a key role in the control of inflammatory pain. However, the nature of opioids produced by T cells is still matter of debate in mice. Whereas β-endorphin has been found in T lymphocytes by using antibody-based methods, messenger RNA (mRNA) quantification shows mainly mRNA encoding for enkephalins. The objective of the study is to elucidate the nature of T cell-derived opioids responsible for analgesia and clarify discrepancy of the results at the protein and genetic levels...
2016: Journal of Neuroinflammation
Eduardo R Butelman, Mary Jeanne Kreek
Opioid receptors (MOP-r, KOP-r, DOP-r, as well as NOP-r) and their endogenous neuropeptide agonist systems are involved in diverse neurobiological and behavioral functions, in health and disease. These functions include pain and analgesia, addictions, and psychiatric diseases (e.g., depression-, anxiety-like, and stress-related disorders). Drug discrimination assays have been used to characterize the behavioral pharmacology of ligands with affinity at MOP-r, KOP-r, or DOP-r (and to a lesser extent NOP-r). Therefore, drug discrimination studies with opioid ligands have an important continuing role in translational investigations of diseases that are affected by these neurobiological targets and their pharmacotherapy...
May 26, 2016: Current Topics in Behavioral Neurosciences
Francesco Resta, Alessio Masi, Maria Sili, Annunziatina Laurino, Flavio Moroni, Guido Mannaioni
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have a key role in the control of cellular excitability. HCN2, a subgroup of the HCN family channels, are heavily expressed in small dorsal root ganglia (DRG) neurons and their activation seems to be important in the determination of pain intensity. Intracellular elevation of cAMP levels activates HCN-mediated current (Ih) and small DRG neurons excitability. GPR35, a Gi/o coupled receptor, is highly expressed in small DRG neurons, and we hypothesized that its activation, mediated by endogenous or exogenous ligands, could lead to pain control trough a reduction of Ih current...
September 2016: Neuropharmacology
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