New pharmacological perspectives and therapeutic options for opioids: Differences matter

Abstract

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. Atypical opioids have and are being developed which not only target the mu opioid receptor but other targets in the pain pathway. Biased mu agonists have been developed but remain ‘unbiased’ clinically. The contribution of drugs targeting non-mu opioid receptors either alone or as heterodimers shows potential promise but remains understudied. That gene splice variants of the mu opioid receptor produce multiple receptor isoforms in different brain regions, and may change with pain chronicity and phenotype, presents new challenges but also opportunities for precision pain medicine. Finally, that opioids also have pro-inflammatory effects not aligned with mu opioid receptor binding affinity implicates a fresh understanding of their role in chronic pain, whether cancer or non-cancer. Hopefully, a new understanding of opioid analgesic drug action may lead to new drug development and better precision medicine in acute and chronic pain relief with less patient harm.

Targeted Therapy for Orofacial Pain: A Novel Perspective for Precision Medicine

“…Opioid analgesics are well established for their use in analgesia, including their abusive risks [ 39 ]. Hopefully, the recent knowledge of opioid analgesic drugs may aid in new drug development for newer therapeutic approaches in precision medicine [ 40 ].…”

Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects

“…M6G is a potent mu agonist which can cause respiratory depression especially in those with reduced kidney function, with no innate immune activation properties. Conversely, M3G has no mu opioid receptor activity but can potently activate the innate immune system by binding to MD2, the accessory protein for TLR4 [2][3][4]. M3G has been implicated in morphine-induced CNS toxicity (seizures, cognitive impairment) at high doses [5,6].…”

Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs

“…Chronic pain is a massive global health burden, with estimated healthcare costs related to pain ranging from 261 to 300 billion USD in the United States alone (Gaskin and Richard, 2012). In spite of this, currently available therapeutic options for chronic pain are limited and have a spectrum of adverse effects (Hylands-White et al, 2017;Somogyi et al, 2022). Alternative Tyagi et al 10.3389/fnmol.2023.1161028 Frontiers in Molecular Neuroscience 02 frontiersin.org treatments for pain that are specific, non-addictive, and effective are an urgent need.…”