Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis

Lambert, David G.

doi:10.1016/j.bjao.2023.100141

Cited by 8 publications

(7 citation statements)

References 138 publications

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Section: Reviewmentioning

confidence: 99%

“…Opioids play a significant role in modulating pain, mood, stress response, and digestion [ 18 , 19 ]. They can control CNCP when alternative therapeutic approaches have proven inadequate in pain management [ 18 ]. This class of drugs is not typically the first line of intervention, due to their potential risks; they are often prescribed when other treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs) or physical therapy have failed to provide sufficient relief [ 2 ].…”

Section: Reviewmentioning

confidence: 99%

“…With a history spanning over 5,000 years, opioids have been employed as analgesics [ 20 ]. Substances like morphine, oxycodone, and hydrocodone bind with the opioid receptors within the central and peripheral nervous system, inducing changes in pain perception and facilitating analgesic effects [ 18 , 19 ].…”

Section: Reviewmentioning

confidence: 99%

“…The mu, kappa, and delta opioid receptors each have unique roles within the modulation of pain and the pharmacological effects of opioids. Mu receptors are primarily responsible for the analgesic and sedative effects of opioids and are known to mediate several adverse effects, including constipation and the risk of respiratory depression [ 18 , 19 ]. In contrast, kappa receptors, while also contributing to analgesia and sedation, are distinguished by their role in inducing aversive affective states and psychotomimetic effects, which encompass altered sensory perceptions and cognitive processes [ 18 , 19 ].…”

Section: Reviewmentioning

confidence: 99%

“…Mu receptors are primarily responsible for the analgesic and sedative effects of opioids and are known to mediate several adverse effects, including constipation and the risk of respiratory depression [ 18 , 19 ]. In contrast, kappa receptors, while also contributing to analgesia and sedation, are distinguished by their role in inducing aversive affective states and psychotomimetic effects, which encompass altered sensory perceptions and cognitive processes [ 18 , 19 ]. The functions of delta receptors, although not as extensively characterized, appear to contribute to pain modulation and may influence emotional regulation, offering a distinct profile of effects from mu and kappa receptors [ 18 , 19 ].…”

Section: Reviewmentioning

confidence: 99%

See 4 more Smart Citations

Adverse Events of the Long-Term Use of Opioids for Chronic Non-cancer Pain: A Narrative Review

Altawili,

Alzarar

et al. 2024

Cureus

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Background: The long-term use of opioids for chronic non-cancer pain (CNCP) has drawn more attention and debate. Although opioids are frequently used to treat chronic pain, their effectiveness and safety over extended periods are still unknown.Objectives: The purpose of this review is to provide an overview of what is currently known about the adverse events of long-term use of opioids in CNCP. It also delivers patient-centered strategies designed to mitigate these risks.Methods: We conducted a literature search in PubMed, MEDLINE, EMBASE, and Web of Science databases. Search terms included CNCP, pain pathophysiology, opioid pharmacodynamics, opioid prescribing trends, guidelines for opioid use, and opioid side effects.Results: Our review highlights that while opioids may provide short-term relief from CNCP, their effectiveness diminishes over time due to the development of opioid tolerance. This tolerance often leads to increased dosages, which can subsequently result in opioid dependence. Additionally, long-term opioid therapy is associated with a spectrum of adverse effects, including constipation, drowsiness, respiratory depression, and potential for drug interactions. Furthermore, our review indicates that alternative pain management strategies play a crucial role in controlling CNCP. They offer significant benefits with fewer adverse events. These strategies include non-opioid medications, physical therapy, cognitive-behavioral therapy (CBT), various interventional procedures, injection therapy, and acupuncture.Conclusion: Using opioids to manage CNCP presents several challenges. Given these challenges, alternative treatments are being considered as viable options. Moreover, it is crucial to customize treatment plans to align with the patients' specific health requirements, existing conditions, and potential risks to ensure the best possible outcomes.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

See 3 more Smart Citations

Adverse Events of the Long-Term Use of Opioids for Chronic Non-cancer Pain: A Narrative Review

Altawili,

Alzarar

et al. 2024

Cureus

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A novel cinnamic and caffeic acid‐conjugated peptide analogs with anticonvulsant and analgesic potency: Comparative analyses of trans/cis isomers

Tchekalarova,

Pechlivanova,

Rangelov

et al. 2024

Drug Development Research

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The novel cinnamic acid (CA) (H4‐CA, H5‐CA, and H7‐CA) and caffeic acid (KA) (H4‐KA, H5‐KA, and H7‐KA) hemorphin analogs have recently been synthesized and their trans isomers have been tested for antiseizure and antinociceptive activity. In the present study, the cis forms of these compounds were tested and compared with their trans isomers in seizure and nociception tests in mice. The cis‐H5‐CA and H7‐CA compounds showed efficacy against psychomotor seizures, whereas the trans isomers were ineffective. Both the cis and trans KA isomers were ineffective in the 6‐Hz test. In the maximal electroshock (MES) test, the cis isomers showed superior antiseizure activity to the trans forms of CA and KA conjugates, respectively. The suppression of seizure propagation by cis‐H5‐CA and the cis‐H5‐KA was reversed by a kappa opioid receptor (KOR) antagonist. Naloxone and naltrindole were not effective. The cis‐isomers of CA conjugates and cis‐H7‐KA produced significantly stronger antinociceptive effects than their trans‐isomers. The cis‐H5‐CA antinociception was blocked by naloxone in the acute phase and by naloxone and KOR antagonists in the inflammatory phase of the formalin test. The antinociception of the KA conjugates was not abolished by opioid receptor blockade. None of the tested conjugates affected the thermal nociceptive threshold. The results of the docking analysis also suggest a model‐specific mechanism related to the activity of the cis‐isomers of CA and KA conjugates in relation to opioid receptors. Our findings pave the way for the further development of novel opioid‐related antiseizure and antinociceptive therapeutics.

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GPR88 impairs the signaling of kappa opioid receptors in a heterologous system and in primary striatal neurons

Rivas-Santisteban,

Lillo,

Garrigós

et al. 2025

Neuropharmacology

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Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis

Cited by 8 publications

References 138 publications

Adverse Events of the Long-Term Use of Opioids for Chronic Non-cancer Pain: A Narrative Review

Adverse Events of the Long-Term Use of Opioids for Chronic Non-cancer Pain: A Narrative Review

A novel cinnamic and caffeic acid‐conjugated peptide analogs with anticonvulsant and analgesic potency: Comparative analyses of trans/cis isomers

GPR88 impairs the signaling of kappa opioid receptors in a heterologous system and in primary striatal neurons

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