Mu-opioid receptor cancer

Kappa-opioid receptors (KOR) are widely expressed throughout the central nervous system, where they modulate a range of physiological processes depending on their location, including stress, mood, reward, pain, inflammation, and remyelination. However, clinical use of KOR agonists is limited by adverse effects such as dysphoria, aversion, and sedation. Within the drug-development field KOR agonists have been extensively investigated for the treatment of many centrally mediated nociceptive disorders including pruritis and pain...

BACKGROUND: We conducted a multicenter, retrospective study on the efficacy and safety of naldemedine in thoracic cancer patients using opioids in clinical practice. METHODS: We retrospectively evaluated thoracic cancer patients treated with naldemedine at 10 institutions in Japan. Clinical data of patients administered naldemedine between June 2017 and August 2019 were extracted from electronic medical records. Inclusion criteria were as follows: (i) patients hospitalized for at least seven days before and after naldemedine administration, and (ii) those whose frequency of defecation was entered in the medical records...

Background: Chronic shoulder pain/disability is a well-recognized side effect of treatment for breast cancer, with ∼40% of patients experiencing this, despite receiving pain management. To manage acute and chronic pain, several opioids are commonly prescribed. Pharmacogenomics have implicated genes within the opioid signaling pathway, including ABCB1 and OPRM1 , to contribute to an individual's variable response to opioids. Aim: To evaluate ABCB1 (rs1045642 G>A, rs1128503 G>A) and OPRM1 (rs1799971 A>G, rs540825 T>A) single-nucleotide polymorphisms (SNPs) in chronic shoulder pain/disability in BCS...

PURPOSE OF REVIEW: Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on antagonists of mu-opioid receptor effect on tumor progression and prognosis in different types of cancers and an evaluation of the available findings on their mechanism of action. RECENT FINDINGS: We have found studies related to methylnaltrexone (MNTX) and naltrexone (NTX) usage in cancer outcomes-related setting...

Opioids are widely used in chronic pain management, despite major concerns about their risk of adverse events, particularly abuse, misuse, and respiratory depression from overdose. Multi-mechanistic opioids, such as tapentadol and buprenorphine, have been widely studied as a valid alternative to traditional opioids for their safer profile. Special interest was focused on the role of the nociceptin opioid peptide (NOP) receptor in terms of analgesia and improved tolerability. Nociceptin opioid peptide receptor agonists were shown to reinforce the antinociceptive effect of mu opioid receptor (MOR) agonists and modulate some of their adverse effects...

Buprenorphine has been widely used in opioid medication assisted treatment (MAT) in the past decade. However, due to misinterpretation of its intrinsic mu opioid receptor activity extrapolated from preclinical and animal data, buprenorphine's clinical application in pain management has been greatly limited. Buprenorphine acts as a full mu agonist with fewer side effects compared to traditional opioids and can be effectively used in the treatment of acute and chronic pain. A strong body of evidence demonstrates that buprenorphine is an effective analgesic agent in both adult and pediatric surgical patients...

BACKGROUND: Opioid and beta-adrenergic receptors are recently shown to cross talk via formation of receptor heterodimers to control the growth and proliferation of breast cancer cells. However, the underlying cell signaling mechanism remained unclear. METHODS: To determine the effect of the interaction of the two systems in breast cancer, we employed triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468, CRISPR or chemical inhibition or activation of beta-adrenergic receptors (B2AR) and mu-opioid receptors (MOR) gene, and PCR array technology and studied aggressive tumor phenotype and signaling cascades...

Constipation is one of the most frequent problems in cancer patients, and its etiology is multifactorial. It leads to decreased quality of life and impedes optimal pain treatment. Despite the high prevalence, constipation is frequently underdiagnosed mainly because of lack of validated diagnostic criteria or widely accepted definition of constipation in cancer patients. All cancer patients should be evaluated regularly for constipation, and concomitant causes and risk factors were assessed. Opioids are responsible for a much of the secondary constipation in cancer patients...

Pain is among the most debilitating symptoms in patients with cancer. Except for their relatively frequent use during end-of-life care, opioids are often, though not routinely, prescribed during the course of the disease. Whereas the clinical phenomena of tolerance, dependence, and addiction are invariably recognized, the molecular mechanisms which effect these outcomes are not fully understood, even among health care professionals. Also uncertain is the possible unfavorable effect of these agents on cancer progression and survival, an association that may be related to the expression of opioid receptors in some tumors...

Opioids are the most popular drugs for both acute and chronic pain management. The G protein-coupled mu-opioid receptor (MOR) is the therapeutic target for most clinically used opioids, including morphine. A mounting number of publications suggest a relationship between the MOR and possible cancer progression and recurrence extending to managing chronic cancer pain. In this study, we studied the possible link between opioid use and pancreatic cancer (PC) progression. We found increased MOR expression in murine and human PC cell lines, human PC-derived organoids, and in the undifferentiated or poorly differentiated areas of surgically resected PC tissues...

Opioids remain the major drug class for the treatment of acute, chronic and cancer pain, but have major harmful effects such as dependence and opioid-induced ventilatory impairment. Although no new typical opioids have come onto the market in the past almost 50 years, a plethora of new innovative formulations has been developed to meet the clinical need. This review is intended to shed light on new understanding of the molecular pharmacology of opioids, which has arisen largely due to the genomic revolution, and what new drugs may become available in the coming years...

BACKGROUND: The opioid agonist D,L-methadone exerts analgesic effects via the mu opioid receptor, encoded by OPRM1 and therefore plays a role in chronic pain management. In preclinical tumor-models D,L-methadone shows apoptotic and chemo-sensitizing effects and was therefore hyped as an off-label "anticancer" drug without substantiation from clinical trials. Its effects in ovarian cancer (OC) are completely unexplored. METHODS: We analyzed OPRM1-mRNA expression in six cisplatin-sensitive, two cisplatin-resistant OC cell-lines, 170 OC tissue samples and 12 non-neoplastic control tissues...

BACKGROUND: Medical benefits of peripherally acting mu-opioid receptor antagonists other than improving opioid-induced constipation remain unclear. Our aim was to evaluate the association between the use of naldemedine and incidence of hyperactive delirium in cancer patients receiving chemotherapy and opioid therapy. METHODS: We conducted a propensity score-matched analysis using a nationwide inpatient database in Japan. Cancer patients receiving both inpatient chemotherapy and opioid therapy from June 1, 2017, to March 31, 2018, were included...

Pain is a common symptom accompanying several clinical conditions and causes serious distress to patients. Addressing pain management is an important aspect of disease treatment, including cancer therapy. Opioid analgesics used to manage pain in human and veterinary medicine have been associated with substance dependence and other adverse effects, thereby limiting their application. Thus, the development of opioid analgesics with good safety profiles with minimal adverse effects and no addictive effects, is presently the focus of pain research...

Opioids are effective in cancer pain management. However, adverse effects such as opioid-induced constipation(OIC) cause significant reductions in the quality-of-life of cancer patients. In addition, this treatment sometimes also results in inadequate pain relief. It is estimated that from 50-90% of cancer patients receiving opioids suffer from OIC. The mechanism of exogenous opioids on gastrointestinal opioid receptors is known to lead to bowel dysfunction: including motility, secretion and coordination of the sphincter function...

BACKGROUND: Clinically, the coadministration of opioids to enhance antinociception and decrease tolerance has attracted increasing research attention. We investigated the effects of dezocine, a mu- and kappa-opioid receptor agonist/antagonist, on morphine tolerance and explored the involvement of opioid receptor expression in a rat model of bone cancer pain. METHODS: Thermal nociceptive thresholds were measured after the subcutaneous injection of morphine (10 mg/kg) alone or combined with dezocine (10 or 1 mg/kg) for 7 consecutive days...

Cancer progression is known to be promoted by increased body stress caused by elevated beta-adrenergic and opioidergic nervous system activities. The effects of β2-adrenergic blocker propranolol (PRO) and μ-opioid receptor antagonist naltrexone (NTX) were tested using a preclinical model of human breast cancer. These drugs, individually, and more potently when combined, inhibited the cell growth and progression of breast cancer cells in vitro in cultures, and in vivo in rat xenografts. The antitumor activities of these drugs were associated with direct cell intrinsic effects, including increased cell growth arrest, elevated levels of apoptotic proteins, and reduced production of epithelial-mesenchymal transition factors by the tumor cells, as well as effects on innate immune activation and reduced inflammatory cytokine levels in plasma...

Bone is one of the preferential target organs of cancer metastasis. Bone metastasis is associated with various complications, of which bone pain is most common and debilitating. The cancer-associated bone pain (CABP) is induced as a consequence of increased neurogenesis, reprogramming and axonogenesis of sensory nerves (SNs) in harmony with sensitization and excitation of SNs in response to the tumor microenvironment created in bone. Importantly, CABP is associated with increased mortality, of which precise cellular and molecular mechanism remains poorly understood...

Background: Bibliometric analysis is used to gain a systematic understanding of developments in the field of the influence of anesthesia on tumor prognosis and changes in research hot spots over the past 20 years. Methods: Relevant publications from the Web of Science Core Collection (WoSCC) were downloaded on May 5, 2021. Acquired data were then analyzed using the Online Analysis Platform of Literature Metrology (https://biblimetric.com) and the CiteSpace software was used to analyze and predict trends and hot spots in this field...

Patients with chronic non-cancer pain (CNCP) often use opioids for long periods of time. This may lead to opioid use disorder (OUD) and psychiatric symptoms: mainly depression and anxiety. The current study investigated the effect of buprenorphine/naloxone (BuNa) rotation on opioid misuse, craving, psychiatric symptoms and pain in patients with CNCP and OUD. Forty-three participants with CNCP and OUD were converted from a full mu-receptor agonist opioid (mean morphine equivalent dose: 328.3 mg) to BuNa, in an inpatient setting...