Morphine for the Treatment of Pain in Sickle Cell Disease

Abstract

Pain is a hallmark of sickle cell disease (SCD) and its treatment remains challenging. Opioids are the major family of analgesics that are commonly used for treating severe pain. However, these are not always effective and are associated with the liabilities of their own. The pharmacology and multiorgan side effects of opioids are rapidly emerging areas of investigation, but there remains a scarcity of clinical studies. Due to opioid-induced endothelial-, mast cell-, renal mesangial-, and epithelial-cell-specific effects and proinflammatory as well as growth influencing signaling, it is likely that when used for analgesia, opioids may have organ specific pathological effects. Experimental and clinical studies, even though extremely few, suggest that opioids may exacerbate existent organ damage and also stimulate pathologies of their own. Because of the recurrent and/or chronic use of large doses of opioids in SCD, it is critical to evaluate the role and contribution of opioids in many complications of SCD. The aim of this review is to initiate inquiry to develop strategies that may prevent the inadvertent effect of opioids on organ function in SCD, should it occur, without compromising analgesia.

Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation

“…Morphine, an opioid, has been the drug of choice for the treatment of severe pain associated with SCA. 1,2 However, morphine is highly histaminergic, and is known to activate mast cells. 2 We showed earlier that mast cells contribute to neurogenic inflammation and hyperalgesia in sickle mice.…”

“…1,2 However, morphine is highly histaminergic, and is known to activate mast cells. 2 We showed earlier that mast cells contribute to neurogenic inflammation and hyperalgesia in sickle mice. 3 We also found that cannabinoids mitigate chronic and hypoxia/reoxygenation (H/R)-evoked acute hyperalgesia in sickle mice.…”

Updated Mechanisms of Sickle Cell Disease-Associated Chronic pain

“…[23,24] Opioids may even produce severe pathological changes in SCD patients that could contribute to organ damage. [25] More targeted treatment options could reduce the need for opioids, and their harmful side effects.…”

Could Perioperative Opioid Use Increase the Risk of Cancer Progression and Metastases?

“…On the other hand opioids can cause side-effects including constipation, respiratory depression and mast cell activation involving peripheral and central mechanisms, and the possibility of addiction. 4 Of significance to the tumor microenvironment and inflammation, opioids interact with endothelium, tumor cells, and inflammatory cells via opioid receptor (OP-R) and non-OP-R mediated mechanisms. 5,6 In the peri-operative setting replete with inflammation, opioids can thus modulate the process of metastasis, which is dependent upon angiogenesis, tumor cell survival and inflammation.…”