Opioid tolerance and opioid-induced hyperalgesia: Is TrkB modulation a potential pharmacological solution?. (1st December 2022)

• Record Type: Journal Article
• Authors: Lim, Sin Yin; Cengiz, Pelin
• Is Part Of: Neuropharmacology. Volume 220(2022)
• Publication Date: 2022-12-01
• Subjects: Pain -- Analgesia -- Opioid -- 7, 8-Dihydroxyflavone -- Tyrosine kinase receptor B; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2022.109260
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Opioids are widely prescribed for moderate to severe pain in patients with acute illness, cancer pain, and chronic noncancer pain. However, long-term opioid use can cause opioid tolerance and opioid-induced hyperalgesia (OIH), contributing to the opioid misuse and addiction crisis. Strategies to mitigate opioid tolerance and OIH are needed to reduce opioid use and its sequelae. Currently, there are few effective pharmacological strategies that reduce opioid tolerance and OIH. The intrinsic tyrosine kinase receptor B (TrkB) ligand, brain-derived neurotrophic factor (BDNF), has been shown to modulate pain. The BDNF-TrkB signaling plays a role in initiating and sustaining elevated pain sensitivity; however, increasing evidence has shown that BDNF and 7, 8-dihydroxyflavone (7, 8-DHF), a potent blood-brain barrier-permeable ligand to TrkB, exert neuroprotective, anti-inflammatory, and antioxidant effects that may protect against opioid tolerance and OIH. As such, TrkB signaling may be an important therapeutic avenue in opioid tolerance and OIH. Here, we review 1) the mechanisms of pain, opioid analgesia, opioid tolerance, and OIH; 2) the role of BDNF-TrkB in pain modulation; and 3) the neuroprotective effects of 7, 8-DHF and their implications for opioid tolerance and OIH. Highlights: Long-term opioid use can cause opioid tolerance and opioid-induced hyperalgesia TrkB and its ligand, brain-derived neurotrophic factor, are involved in pain modulation 7, 8-dihydroxyflavone, a TrkB agonist, exerts neuroprotective effects that may prevent opioid tolerance and opioid-induced hyperalgesia