The role of morphine in regulation of cancer cell growth

Morphine is considered the “gold standard” for relieving pain and is currently one of the most effective drugs available clinically for the management of severe pain associated with cancer. In addition to its use in the treatment of pain, morphine appears to be important in the regulation of neoplastic tissue. Although morphine acts directly on the central nervous system to relieve pain, its activities on peripheral tissues are responsible for many of the secondary complications. Therefore, understanding the impact, other than pain control, of morphine on cancer treatment is extremely important. The effect of morphine on tumor growth is still contradictory, as both growth-promoting and growth-inhibiting effects have been observed. Accumulating evidence suggests that morphine can affect proliferation and migration of tumor cells as well as angiogenesis. Various signaling pathways have been suggested to be involved in these extra-analgesic effects of morphine. Suppression of immune system by morphine is an additional complication. This review provides an update on the influence of morphine on the growth and migration potential of tumor cells

Novel Endomorphin Analogs Are More Potent and Longer-Lasting Analgesics in Neuropathic, Inflammatory, Postoperative, and Visceral Pain Relative to Morphine.

Activation of the mu-opioid receptor provides the gold standard for pain relief, but most opioids used clinically have adverse effects that have contributed to an epidemic of overdose deaths. We recently characterized mu-opioid receptor selective endomorphin (EM) analogs that provide potent antinociception with reduction or absence of a number of side effects of traditionally prescribed opioids including abuse liability, respiratory depression, motor impairment, tolerance, and inflammation. The current study explores the effectiveness of these EM analogs relative to morphine in four major pain models by intrathecal as well as intravenous administration in male Sprague Dawley rats and subcutaneous administration in male CD-1 mice. In the spared nerve injury model of neuropathic pain, mechanical allodynia and mechanical hyperalgesia were assessed with von Frey and Randall-Selitto tests, respectively. In the paw incision model of postoperative pain, von Frey testing was used to assess mechanical allodynia and thermal hyperalgesia was evaluated with Hargreaves testing. In the Complete Freund\u27s Adjuvant model of inflammatory pain, thermal hyperalgesia was assessed using Hargreaves testing. In CD-1 mice, visceral pain was assessed with the acetic acid writhing test. In all cases, EM analogs had equal or greater potency and longer duration of action relative to morphine. The data suggest that EM analogs, particularly analog 4 (ZH853), could provide effective therapy for a diverse spectrum of pain conditions with low risk of adverse side effects compared with currently used opioids such as morphine. PERSPECTIVE: Novel EM analogs show equal or greater potency and effectiveness relative to morphine in multiple pain models. Together with substantially reduced side effects, including abuse liability, the compounds show promise for addressing the critical need for effective pain relief as well as reducing the opioid overdose epidemic. J Pain 2017 Dec; 18(12):1526-1541

Implications of preoperative administration of aspirin in patients undergoing coronary artery bypass grafting

AbstractThe perioperative consequences of preoperative aspirin administration were assessed in a large prospective cooperative study of 772 patients undergoing coronary artery bypass grafting. The 772 patients were randomized to receive either aspirin (325 mg once a day), aspirin (325 mg three times a day), aspirin plus dipyridamole (325 and 75 mg together three times a day) (aspirin group), sulfinpyrazone (267 mg three times a day) or placebo (nonaspirin group). The therapy, except in the aspirin group, was started 48 h before the operation. In all aspirin subgroups, one 325 mg aspirin dose was given 12 h before surgery and maintained thereafter according to the assigned regimen.Patients in the aspirin group had significantly more postoperative bleeding and received more packed blood cells and blood products than did patients in the nonaspirin group. Although total operative duration and cardiopulmonary bypass duration were not different, the interval between completion of cardiopulmonary bypass and wound closure was significantly longer (p = 0.035) in the aspirin group. Thirty-one (6.6%) of 471 patients in the aspirin group and 5 (1.7%) of 301 patients in the nonaspirin group also required reoperation for control of postoperative bleeding (p = 0.002). The site of bleeding found at reoperation was not different between the two groups. There was no difference in operative mortality rates, incidence of other bleeding complications or occurrence of other postoperative complications between the two groups.Thus, antiplatelet regimens involving preoperative initiation of aspirin therapy, which has been shown to improve graft patency, increase the risk of abnormal postoperative bleeding and the need for reoperation. These observations prompted a prospective clinical trial to compare the benefits and risks of preoperative versus early postoperative administration of aspirin. Until the results of the new trial are known, the data from the current study should be taken into consideration for risk assessment of patients undergoing coronary artery bypass grafting