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morphine tolerance

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https://www.readbyqxmd.com/read/28343361/genetic-dissociation-of-morphine-analgesia-from-hyperalgesia-in-mice
#1
Gina F Marrone, Valerie Le Rouzic, Andras Varadi, Jin Xu, Anjali M Rajadhyaksha, Susruta Majumdar, Ying-Xian Pan, Gavril W Pasternak
RATIONALE: Morphine is the prototypic mu opioid, producing its analgesic actions through traditional 7 transmembrane domain (7TM) G-protein-coupled receptors generated by the mu opioid receptor gene (Oprm1). However, the Oprm1 gene undergoes extensive alternative splicing to yield three structurally distinct sets of splice variants. In addition to the full-length 7TM receptors, it produces a set of truncated variants comprised of only 6 transmembrane domains (6TM). OBJECTIVES: This study explored the relative contributions of 7TM and 6TM variants in a range of morphine actions...
March 25, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28333865/clinical-application-of-perioperative-multimodal-analgesia
#2
Jörgen Bruhn, Gert J Scheffer, Geert-Jan van Geffen
PURPOSE OF REVIEW: The experience of intense postoperative pain remains a significant problem in perioperative medicine. The mainstay of postoperative analgetic therapy is the combination of nonopioid agents (e.g. paracetamol and NSAIDs) with strong opioids (e.g. morphine) according to the WHO analgesic ladder. But as the incidence and intensity of postoperative pain remains high, the search for and evaluation of additional concepts is ongoing. This review highlights the current trends of perioperative multimodal analgesia concepts...
March 22, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28319053/alternatively-spliced-mu-opioid-receptor-c-termini-impact-the-diverse-actions-of-morphine
#3
Jin Xu, Zhigang Lu, Ankita Narayan, Valerie P Le Rouzic, Mingming Xu, Amanda Hunkele, Taylor G Brown, William F Hoefer, Grace C Rossi, Richard C Rice, Arlene Martínez-Rivera, Anjali M Rajadhyaksha, Luca Cartegni, Daniel L Bassoni, Gavril W Pasternak, Ying-Xian Pan
Extensive 3' alternative splicing of the mu opioid receptor gene OPRM1 creates multiple C-terminal splice variants. However, their behavioral relevance remains unknown. The present study generated 3 mutant mouse models with truncated C termini in 2 different mouse strains, C57BL/6J (B6) and 129/SvEv (129). One mouse truncated all C termini downstream of Oprm1 exon 3 (mE3M mice), while the other two selectively truncated C-terminal tails encoded by either exon 4 (mE4M mice) or exon 7 (mE7M mice). Studies of these mice revealed divergent roles for the C termini in morphine-induced behaviors, highlighting the importance of C-terminal variants in complex morphine actions...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318323/sublingual-transdermal-and-intravenous-patient-controlled-analgesia-for-acute-post-operative-pain-systematic-literature-review-and-mixed-treatment-comparison
#4
Pablo Katz, Shweta Takyar, Pamela Palmer, Hiltrud Liedgens
OBJECTIVE: To conduct a systematic literature review (SLR) and quantitative analysis to assess the comparative efficacy and safety of the sufentanil sublingual tablet system (SSTS) against other available patient controlled analgesia (PCA) options for post-operative analgesia. METHODS: An SLR was conducted for studies published between 2004 and 2016. Due to study heterogeneity, subgroup analyses were conducted controlling for differences in imputation methods for missing values, baseline pain severity, and type of surgery...
March 20, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28302576/adolescent-chronic-escalating-morphine-administration-induces-long-lasting-changes-in-tolerance-and-dependence-to-morphine-in-rats
#5
Hamed Salmanzadeh, Hossein Azizi, Saeed Semnanian
Adolescence is a gradual period of transition from childhood to adulthood. It is considered as a sensitive developmental time point that long lasting changes occur in the brain. The present study examined adolescent chronic escalating morphine administration on morphine tolerance and dependence in adulthood. Adolescent male Wistar rats (30days old) were administered increasing doses of morphine (2.5 to 25mg/kg, s.c.) every 12h, for 10days. Control rats received saline according to the same protocol. Thereafter, during adulthood (65-75days old), tolerance to antinociceptive effect of morphine was induced by subcutaneous injection of 3mg/kg morphine, once a day for 7days...
March 14, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28294636/indirect-treatment-comparison-of-two-non-invasive-patient-controlled-analgesia-treatments-for-acute-post-operative-pain-management
#6
Pablo Katz, Shweta Takyar, Pamela Palmer, Hiltrud Liedgens
OBJECTIVES: To evaluate the relative clinical efficacy, safety, and tolerability associated with two non-invasive patient-controlled analgesia (PCA) treatments, sufentanil sublingual tablet system (SSTS) and fentanyl iontophoretic patient-controlled transdermal system (PCTS). These two treatments have recently been approved in the EU for the management of acute moderate-to-severe post-operative pain in adult patients. METHODS: As no head-to-head trials comparing SSTS and PCTS currently exist, indirect treatment comparison (ITC) analyses were conducted to evaluate SSTS or PCTS versus intravenous (IV) morphine PCA...
March 15, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28282499/non-opioid-medications-for-the-relief-of-chronic-breathlessness-current-evidence
#7
Carlo Barbetta, David C Currow, Miriam J Johnson
To evaluate systematically randomised clinical trials investigating non-opioid medications for the management and treatment of chronic breathlessness. Areas covered: The evidence for the role of benzodiazepines, anxiolytics, selective serotonin re-uptake inhibitors (SSRIs), tricyclic antidepressants, antihistamines, cannabinoids, nebulized furosemide and herbal-based treatments were critically reviewed. Search of the Clinical Trials Registry (Clinicaltrial.gov) identified ongoing studies expected to generate new data in the near future in several classes of non-opioid medications for their net effect on chronic breathlessness...
March 17, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28280004/connexin-purinergic-signaling-in-enteric-glia-mediates-the-prolonged-effect-of-morphine-on-constipation
#8
Sukhada Bhave, Aravind Gade, Minho Kang, Kurt F Hauser, William L Dewey, Hamid I Akbarali
Morphine is one of the most widely used drugs for the treatment of pain. However, side effects, including persistent constipation and antinociceptive tolerance limit its clinical efficacy. Prolonged morphine treatment results in a "leaky" gut predisposing to colonic inflammation that is facilitated by microbial dysbiosis and associated bacterial translocation. In this study, we examined the role of enteric glia in mediating this secondary inflammatory response to prolonged treatment with morphine. We found that purinergic P2X receptor activity was significantly enhanced in enteric glia that were isolated from mice with long-term morphine treatment (in vivo) but not upon direct exposure of glia to morphine (in vitro)...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28267064/nerve-injury-induced-epigenetic-silencing-of-opioid-receptors-controlled-by-dnmt3a-in-primary-afferent-neurons
#9
Linlin Sun, Jian-Yuan Zhao, Xiyao Gu, Lingli Liang, Shaogen Wu, Kai Mo, Jian Feng, Weixiang Guo, Jun Zhang, Alex Bekker, Xinyu Zhao, Eric J Nestler, Yuan-Xiang Tao
Opioids are the gold standard for pharmacological treatment of neuropathic pain, but their analgesic effects are unsatisfactory in part due to nerve injury-induced downregulation of opioid receptors in dorsal root ganglia (DRG) neurons. How nerve injury drives such downregulation remains elusive. DNA methyltransferase-(DNMT-) triggered DNA methylation represses gene expression. We show here that blocking the nerve injury-induced increase in DRG DNMT3a (a de novo DNMT) rescued the expression of Oprm1 and Oprk1 mRNAs and their respective encoding mu opioid receptor (MOR) and kappa opioid receptor (KOR) proteins in the injured DRG...
March 4, 2017: Pain
https://www.readbyqxmd.com/read/28243713/mper1-promotes-morphine-induced-locomotor-sensitization-and-conditioned-place-preference-via-histone-deacetylase-activity
#10
Stéphanie Perreau-Lenz, Laura-Sophie Hoelters, Sarah Leixner, Carla Sanchis-Segura, Anita Hansson, Ainhoa Bilbao, Rainer Spanagel
RATIONALE: Previous studies have shown that repeated exposure to drugs of abuse is associated with changes in clock genes expression and that mice strains with various mutations in clock genes show alterations in drug-induced behaviors. OBJECTIVE: The objective of this study is to characterize the role of the clock gene mPer1 in the development of morphine-induced behaviors and a possible link to histone deacetylase (HDAC) activity. METHODS: In Per1 (Brdm1) null mutant mice and wild-type (WT) littermates, we examined whether there were any differences in the development of morphine antinociception, tolerance to antinociception, withdrawal, sensitization to locomotion, and conditioned place preference (CPP)...
February 28, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28237804/s-adenosyl-methionine-sam-attenuates-the-development-of-tolerance-to-analgesic-activity-of-morphine-in-rats
#11
Jatinder Katyal, Hemant Kumar, Dinesh Joshi, Yogendra Kumar Gupta
BACKGROUND: Development of tolerance to analgesic effect, on chronic administration of morphine, limits its clinical usefulness in pain management. S-adenosyl methionine (SAM) used for arthritis and approved as a supplement in many countries including United States was evaluated for reducing morphine tolerance. METHODS: Male 'Wistar' rats were used. The analgesic activity was determined using tail flick analgesiometer (Columbus Instruments, USA). Rats given morphine (7mg/kg), intraperitoneally (i...
February 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28230181/dezocine-exhibits-antihypersensitivity-activities-in-neuropathy-through-spinal-%C3%AE-opioid-receptor-activation-and-norepinephrine-reuptake-inhibition
#12
Yong-Xiang Wang, Xiao-Fang Mao, Teng-Fei Li, Nian Gong, Ma-Zhong Zhang
Dezocine is the number one opioid painkiller prescribed and sold in China, occupying 44% of the nation's opioid analgesics market today and far ahead of the gold-standard morphine. We discovered the mechanisms underlying dezocine antihypersensitivity activity and assessed their implications to antihypersensitivity tolerance. Dezocine, given subcutaneously in spinal nerve-ligated neuropathic rats, time- and dose-dependently produced mechanical antiallodynia and thermal antihyperalgesia, significantly increased ipsilateral spinal norepinephrine and serotonin levels, and induced less antiallodynic tolerance than morphine...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28226414/methylene-blue-for-the-treatment-of-intractable-pain-associated-with-oral-mucositis
#13
Carlos J Roldan, Kent Nouri, Thomas Chai, Billy Huh
Oral mucositis is a common and often debilitating complication among cancer patients receiving radiation therapy to the head and neck or chemotherapy agents, or undergoing hematopoietic stem cell transplantation. Pain and decreased oral function associated with oral mucositis may persist long after the conclusion of therapy. Although most patients respond to conservative management, a subset of patients develop intractable pain with severe consequences. For some, the use of total parenteral nutrition with insertion of percutaneous endoscopic gastrostomy feeding tubes is the only alternative...
February 22, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28220483/pharmacokinetics-and-pharmacodynamics-of-metamizol-in-co-administration-with-morphine-under-acute-and-chronic-treatments-in-arthritic-rats
#14
Patricia Esmeralda Carrillo-Calzadilla, Francisco Javier López-Muñoz, Luis Alfonso Moreno-Rocha, José Raúl Medina-López, Alma Rosa Cortés-Arroyo, Adriana Miriam Domínguez-Ramírez
OBJECTIVE: To investigate the relationship between metamizol pharmacokinetics and the antinociceptive effect produced after subcutaneous administration of metamizol (177.8 mg/kg) alone or in combination with morphine (3.2 mg/kg), under acute and chronic treatments. METHODS: Antinociception was assessed using the pain-induced functional impairment model in rat (PIFIR). Serial blood samples were collected from the same animals to study the pharmacokinetics of metamizol...
February 21, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#15
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28211545/the-effect-of-gut-microbiome-on-tolerance-to-morphine-mediated-antinociception-in-mice
#16
Minho Kang, Ryan A Mischel, Sukhada Bhave, Essie Komla, Alvin Cho, Charity Huang, William L Dewey, Hamid I Akbarali
There is growing appreciation for the importance of gastrointestinal microbiota in many physiological and pathophysiological processes. While morphine and other narcotics are the most widely prescribed therapy for moderate to severe pain clinically, they have been noted to alter microbial composition and promote bacterial translocation to other tissues. Here we examined the pharmacodynamic properties of chronic morphine in mice following bacterial depletion with oral gavage of an antibiotic cocktail (ABX). ABX significantly reduced gut bacteria and prevented chronic morphine induced increases in gut permeability, colonic mucosal destruction, and colonic IL-1β expression...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179123/spinal-or-supraspinal-phosphorylation-deficiency-at-the-mor-c-terminus-does-not-affect-morphine-tolerance-in-vivo
#17
Cherkaouia Kibaly, Hong-Yiou Lin, Horace H Loh, Ping-Yee Law
The development of tolerance to morphine, one of the most potent analgesics, in the management of chronic pain is a significant clinical problem and its mechanisms are poorly understood. Morphine exerts its pharmacological effects via the μ-opioid receptor (MOR). Tolerance is highly connected to G-protein-coupled receptors (GPCR) phosphorylation and desensitization increase. Because morphine desensitization previously has been shown to be MOR phosphorylation- and ß-arrestin2-independent (in contrast to agonists such as fentanyl), we examined the contribution of phosphorylation of the entire C-terminus to the development of antinociceptive tolerance to the partial (morphine) and full (fentanyl) MOR agonists in vivo...
February 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28178176/nlrp12-inflammasome-expression-in-the-rat-brain-in-response-to-lps-during-morphine-tolerance
#18
Sulie L Chang, Wenfei Huang, Xin Mao, Sabroni Sarkar
Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12 (NLRP12) inflammasome has been reported to have anti-inflammatory activity. In this study, we examined the expression of NLRP12 inflammasome related genes in the adult F344 rat brain in response to the bacterial endotoxin lipopolysaccharide (LPS) in the presence and absence of morphine tolerance...
February 6, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28177515/methadone-for-cancer-pain
#19
REVIEW
Alexander B Nicholson, Graeme R Watson, Sheena Derry, Philip J Wiffen
BACKGROUND: This is an updated review originally published in 2004 and first updated in 2007. This version includes substantial changes to bring it in line with current methodological requirements. Methadone is a synthetic opioid that presents some challenges in dose titration and is recognised to cause potentially fatal arrhythmias in some patients. It does have a place in therapy for people who cannot tolerate other opioids but should be initiated only by experienced practitioners. This review is one of a suite of reviews on opioids for cancer pain...
February 8, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28162682/-435-nausea-and-vomiting-with-oliceridine-trv130-a-novel-%C3%AE-receptor-g-protein-pathway-selective-modulator-%C3%AE-gps-vs-morphine-an-analysis-of-tolerability-from-a-phase-2b-randomized-clinical-trial
#20
H Minkowitz, N Singla, D Soergel, D Burt, F Skobieranda
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
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