Cancer Pain Management: Opioid Analgesics, Part 2

Abstract

Opioid analgesics are the cornerstone of moderate to severe cancer pain management, and do not have ceiling doses unless unmanageable adverse effects occur. Oral, short-acting pure μ agonists such as morphine are most frequently used, but other agents and administration formulations allow finding the right opioid and dose for most patients. In addition, clinicians must understand the metabolism, pharmacokinetics, and elimination of particular drugs to individualize opioid selection, select initial doses, and appropriately escalate doses to satisfactory pain relief or uncontrollable toxicity. Anticipation and proactive management of possible adverse effects, particularly constipation, confusion or delirium, opioid-specific adverse effects, and opioid abuse, are also integral to primary and secondary prophylaxis and management.

Negative allosteric modulation of cannabinoid CB1receptor signaling suppresses opioid-mediated tolerance and withdrawal without blocking opioid antinociception

“…The opioid epidemic remains an issue of great concern that has led to innumerable drug overdose deaths globally [1][2][3]. While opioids continue to be prescribed for relieving cancer, postoperative and neuropathic pain [4][5][6], their chronic clinical use is limited by adverse side-effects, including analgesic tolerance, physical dependence, withdrawal, constipation, respiratory depression and, in extreme cases, a fatal overdose [7][8][9][10][11][12]. Therefore, novel therapeutic strategies that can spare opioid analgesic efficacy while circumventing their unwanted side-effects remain an urgent and unmet therapeutic need.…”

Activation of spinal PDGFRβ in microglia promotes neuronal autophagy via p38 MAPK pathway in morphine‐tolerant rats

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Morphine is the most potent analgesic in clinical treatment for various painful conditions. Long-term usage of morphine inevitably leads to the development of antinociceptive tolerance, which limits its clinical utilization (Christie, 2008;Wickham, 2017). For several decades, numerous studies have been devoted to illuminating the mechanisms underlying morphine tolerance, including nitric oxide-cyclic 3'-5' guanosine monophosphate signaling pathway, α 2 noradrenergic system cannabinoid system, and hyperexcitability of the central nervous system (Fisher et al, 2019;Gursoy et al, 2011;Ozdemir, 2020;Ozdemir et al, 2011).

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