Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO?

Gledhill, Laura J; Babey, Anna‐Marie

doi:10.1007/s10571-021-01065-8

Cited by 12 publications

(8 citation statements)

References 254 publications

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“…(2) Cellular adaptations, which include gene expression [113][114][115] and the reduction in MOR function. An exemplar study of the latter is that increased activity of NMDAR by PKC/PKA-induced phosphorylation of its GluN2A and GluN2B subunits leads to higher calcium influx, increased release of NO, and subsequent negative regulation of MOR activity [116].…”

Section: Egfr and Nmda Receptor Interactionsmentioning

confidence: 99%

Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance

Santi,

Zhang,

Liu

et al. 2023

Pharmaceuticals

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Oral cancer pain remains a significant public health concern. Despite the development of improved treatments, pain continues to be a debilitating clinical feature of the disease, leading to reduced oral mobility and diminished quality of life. Opioids are the gold standard treatment for moderate-to-severe oral cancer pain; however, chronic opioid administration leads to hyperalgesia, tolerance, and dependence. The aim of this review is to present accumulating evidence that epidermal growth factor receptor (EGFR) signaling, often dysregulated in cancer, is also an emerging signaling pathway critically involved in pain and opioid tolerance. We presented preclinical and clinical data to demonstrate how repurposing EGFR inhibitors typically used for cancer treatment could be an effective pharmacological strategy to treat oral cancer pain and to prevent or delay the development of opioid tolerance. We also propose that EGFR interaction with the µ-opioid receptor and glutamate N-methyl-D-aspartate receptor could be two novel downstream mechanisms contributing to pain and morphine tolerance. Most data presented here support that repurposing EGFR inhibitors as non-opioid analgesics in oral cancer pain is promising and warrants further research.

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Section: Egfr and Nmda Receptor Interactionsmentioning

confidence: 99%

Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance

Santi,

Zhang,

Liu

et al. 2023

Pharmaceuticals

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“…Morphine binds to adenyl cyclase inhibitory receptors, increasing of adenly cyclase causes an increase in protein kinase which will activate the nmda receptor to bind to glutamate. Continuous exposure will lead to calcium bind with calmodulin and activates calmodulin kinase thus NO upregulation is not well tolerated, and the cycle remains unchanged [30] .In some cases where the effect of tolerance increases, it will lead to addiction. HBOT has a role in suppressing addiction to codeine needs through several mechanisms, mainly by monoaminergic receptor [28].…”

Section: Hyperbaric Oxygen Therapy Mechanism As a Potential Choice To Reduce Codeine Addictionmentioning

confidence: 99%

“…An increase in NO will stimulate a further increase in GHG and NO synthase (NOS). GHG has a role in decreasing GABA, while NOS stimulates an increase in NO production [30]. The increase in NO and the effect of HBOT on decreasing GABA will cause an increase in dopamine in the body, this will cause depolarization of cells and ultimately cause a stimulant effect.…”

Section: Hyperbaric Oxygen Therapy Mechanism As a Potential Choice To Reduce Codeine Addictionmentioning

confidence: 99%

The Potential of Hyperbaric Oxygen Therapy Against Codeine Addiction Reduction

Rizal¹,

Pura²,

Herawati³

2021

IJRP

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Excessive opioid usage such as codeine can lead to anxiety, dose dependency, and addiction. Furthermore, drug addiction induce intoxication and in some case death. Several approach can be done to treat codein abuse. Hyberbaric oxygen is one of the therapy choices, considered that it can be used as main and supporting management. Related studies said increasing level of Nitric Oxide (NO) and Dopaminergic, main substances in drug addiction, can be inhibited by hyperbaric oxygen therapy thus it has the potential value to reduce narcotic addiction such as codeine. However, the review papers of previous research is rare. Therefore, this article discussed codeine, hyperbaric oxygen therapy (HBO), and its relation to decrease level of codein addiction, based on scientific literatures. In conclusion, HBO treatment has a potential correlation to minimize the effects of opioid withdrawal, since it can induce nitric oxide and involves the control of monoaminergic neurotransmitters that reduce withdrawal effects.

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“…The application of ketamine as an analgesic adjuvant strategy (1,2) to reduce the induction of opioid analgesic tolerance is based on the well-established observation that antagonism of NMDA receptors reduces the development of opioid analgesic tolerance (6). More than thirty years of pharmacological studies have shown that antagonism of the NMDA receptor (6)(7)(8)(9)(10) or inhibition of the nitric oxide synthase (NOS) enzyme (10)(11)(12) inhibits the induction of opioid-induced analgesic tolerance.…”

Section: Introductionmentioning

confidence: 99%

Adeno-associated virus-mediated gene transfer of arginine decarboxylase to the central nervous system prevents opioid analgesic tolerance

Churchill,

Peterson,

Kitto

et al. 2024

Front. Pain Res.

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Agmatine, a decarboxylated form of L-arginine, prevents opioid analgesic tolerance, dependence, and self-administration when given by both central and systemic routes of administration. Endogenous agmatine has been previously detected in the central nervous system. The presence of a biochemical pathway for agmatine synthesis offers the opportunity for site-specific overexpression of the presumptive synthetic enzyme for local therapeutic effects. In the present study, we evaluated the development of opioid analgesic tolerance in ICR-CD1 mice pre-treated with either vehicle control or intrathecally delivered adeno-associated viral vectors (AAV) carrying the gene for human arginine decarboxylase (hADC). Vehicle-treated or AAV-hADC-treated mice were each further divided into two groups which received repeated delivery over three days of either saline or systemically-delivered morphine intended to induce opioid analgesic tolerance. Morphine analgesic dose-response curves were constructed in all subjects on day four using the warm water tail flick assay as the dependent measure. We observed that pre-treatment with AAV-hADC prevented the development of analgesic tolerance to morphine. Peripheral and central nervous system tissues were collected and analyzed for presence of hADC mRNA. In a similar experiment, AAV-hADC pre-treatment prevented the development of analgesic tolerance to a high dose of the opioid neuropeptide endomorphin-2. Intrathecal delivery of anti-agmatine IgG (but not normal IgG) reversed the inhibition of endomorphin-2 analgesic tolerance in AAV-hADC-treated mice. To summarize, we report here the effects of AAV-mediated gene transfer of human ADC (hADC) in models of opioid-induced analgesic tolerance. This study suggests that gene therapy may contribute to reducing opioid analgesic tolerance.

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Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO?

Cited by 12 publications

References 254 publications

Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance

Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance

The Potential of Hyperbaric Oxygen Therapy Against Codeine Addiction Reduction

Adeno-associated virus-mediated gene transfer of arginine decarboxylase to the central nervous system prevents opioid analgesic tolerance

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