Selective up‐regulation of functional mu‐opioid receptor splice variants by chronic opioids

Abstract We recently reported (Verzillo, et al. J. Neurochem: 130, 790–796, 2014) that chronic systemic morphine selectively up‐regulates mRNA encoding two C‐terminal μ‐opioid receptor (MOR) splice variants, MOR‐1C1 and MOR‐1B2 (MOR‐1B2/‐1C1). Given the known disconnects between changes in levels of mRNA and corresponding protein, it is essential to directly demonstrate that chronic opioid treatment elevates functional MOR‐1B2/‐1C1 protein prior to inferring relevance of these MOR variants to spinal opioid tolerance mechanisms. Accordingly, we investigated the ability of chronic opioid exposure to up‐regulate MOR protein in Chinese hamster ovary cells stably transfected with rat MOR variants MOR‐1B2, MOR‐1C1, or MOR‐1 (considered to be the predominant MOR). Findings revealed that chronic treatment with the clinically relevant opioids morphine, oxycodone and hydrocodone substantially up‐regulated membrane MOR‐1B2/‐1C1 protein. This up‐regulation was abolished by the protein synthesis inhibitor cycloheximide, eliminating contributions from receptor redistribution. The increment in MOR‐1B2/‐1C1 protein was paralleled by a significant increment in opioid agonist‐stimulated GTPγS‐binding (reflective of increased aggregate MOR G protein coupling) indicating that up‐regulated MOR‐1B2/‐1C1 represented functional receptors. Strikingly, these tolerance‐associated adaptations of MOR‐1B2/‐1C1 differed considerably ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Original Article Source Type: research

Related Links:

Abstract BACKGROUND: Opioids are effective analgesics in the management of chronic pain. However, their clinical use is hindered by adverse side effects such as addiction and analgesic tolerance. Naringenin is a common polyphenolic constituent of the citrus fruits and is one of the most commonly consumed flavonoids within our regular diet. However, its influences on opioid tolerance and addiction have not yet been clarified. OBJECTIVES: To examine the effect of different doses of naringenin on analgesic tolerance, conditioned place preference and neuroinflammation in morphine-exposed rats. METHODS: Analg...
Source: The American Journal of Drug and Alcohol Abuse - Category: Addiction Authors: Tags: Am J Drug Alcohol Abuse Source Type: research
umdar Achieving effective pain management is one of the major challenges associated with modern day medicine. Opioids, such as morphine, have been the reference treatment for moderate to severe acute pain not excluding chronic pain modalities. Opioids act through the opioid receptors, the family of G-protein coupled receptors (GPCRs) that mediate pain relief through both the central and peripheral nervous systems. Four types of opioid receptors have been described, including the μ-opioid receptor (MOR), κ-opioid receptor (KOR), δ-opioid receptor (DOR), and the nociceptin opioid peptide recept...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
This week is Te Wiki o te Maori – and the theme is Kia Kaha te Reo Maori. For those readers not familiar with te reo, kia kaha translates to “be strong.” It’s a word people from Otautahi (Christchurch) have used a lot since 2010 and the first of the many events that have shaken (literally) our world since then. Te Wiki o te Maori is a week dedicated to celebrating and strengthening the use of Maori language in New Zealand. While the week celebrates the language of Aotearoa, it also helps us tangata tiriti, or people of the Treaty of Waitangi, remember that we have a place in this whenua (land). ...
Source: HealthSkills Weblog - Category: Anesthesiology Authors: Tags: Chronic pain Pain conditions Professional topics Research Resilience/Health Science in practice respect values Source Type: blogs
Having trouble viewing this email? View it as a Web page. NIDCR's Fall 2020 E-Newsletter In this issue: NIDCR News Funding Opportunities NIH/HHS News Funding Notices Science Advances Subscribe to NICDR News Grantee News   NIDCR News NIDCR Announces Availability of COVID-19 Research Funding On May 5, NIDCR issued two Notices of Special Interest highlighting the urgent need for research on coronavirus disease 2019. This research may be conducted either via the National Dental PBRN infrastructu...
Source: NIDCR Science News - Category: Dentistry Source Type: news
A couple of weeks back I posted about my concerns that exercise is often over-hyped, has limited effects on pain and disability, and therefore people going through a rehabilitation programme will likely dump doing the exercises as soon as the programme ends. Well, that was an interesting conversation starter! TBH I expected the response. On the one hand we have avid strength and conditioning people (including a whole bunch of physiotherapists) saying it’s crucial to get strong and fit because it’s good for health and longevity, while on the other hand we have a large group of “others” who think life...
Source: HealthSkills Weblog - Category: Anesthesiology Authors: Tags: Chronic pain Clinical reasoning Pain conditions Professional topics Research Science in practice goal setting Source Type: blogs
Over the past decade, increased awareness by the medical profession of the devastating consequences of opioid addiction has resulted in substantial efforts to limit the number of opioid prescriptions for both perioperative pain management and chronic pain. While these efforts have had some success, opioid misuse remains a crisis, which we in the orthopaedic community have a particular opportunity to address. It is the belief of the undersigned that progress depends on improved research methods and reporting to further the understanding of pain experience and response to management, with the end goal of identifying more eff...
Source: The Spine Journal - Category: Orthopaedics Authors: Tags: Editorial Source Type: research
By LINDA T. HAND Every day, we make thousands of choices. Some of them – even those that seem trivial at the time – will change the course of our lives. This concept was memorably illustrated in the 1998 film Sliding Doors, which imagined two very different paths for Gywneth Paltrow’s character, Helen, based entirely on whether or not she makes or misses the London Tube on her commute home—the film’s eponymous sliding doors.  Helen doesn’t have the luxury of weighing her possible futures and altering her choices accordingly, perhaps quickening her pace or stopping for a la...
Source: The Health Care Blog - Category: Consumer Health News Authors: Tags: Health Tech Health Technology Linda Hand Prealize Health proactive healthcare Source Type: blogs
Having trouble viewing this email? View it as a Web page. NIDCR's Summer 2020 E-Newsletter In this issue: NIDCR News Funding Opportunities NIH/HHS News Funding Notices Science Advances Subscribe to NICDR News Grantee News   NIDCR News NIDCR Announces Availability of COVID-19 Research Funding On May 5, NIDCR issued two Notices of Special Interest highlighting the urgent need for research on coronavirus disease 2019. This research may be conducted either via the National Dental PBRN infrastruc...
Source: NIDCR Science News - Category: Dentistry Source Type: news
  Cannabis, weed, marijuana, pot. It goes by several names, but we all know what it smells like. As weed becomes more mainstream, we on the Not Crazy podcast want to know: Is marijuana really an effective treatment for anxiety? Is it just a coping mechanism? Or a vice? In today’s podcast, Gabe and Jackie look at the research and weigh out the evidence. They also interview Eileen Davidson, a rheumatoid arthritis patient who regularly uses marijuana as a medicine to see what she has to say. What’s your take? Tune in for an open-minded discussion about weed. (Transcript Available Below) SUBSCRIBE &REV...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: Anxiety and Panic General Medications Not Crazy Podcast Source Type: blogs
Conclusion. Patients on chronic opioids prior to spine surgery are more likely to have a longer hospital stay and continue on opioids for a longer time after surgery, compared with patients not on chronic opioid therapy. Spine surgeons and pain specialists should seek to identify patients on chronic opioids before surgery and evaluate strategies to optimize pain management in the pre- and postoperative course. Level of Evidence: 3
Source: Spine - Category: Orthopaedics Tags: CLINICAL CASE SERIES Source Type: research
More News: Addiction | Back Pain | Chronic Pain | Hydrocodone | Morphine | Neurology | Neuroscience | Ovaries | Oxycodone | OxyContin | Pain | Pain Management