Molecular and Epigenetic Aspects of Opioid Receptors in Drug Addiction and Pain Management in Sport
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Opioid receptors, including the μ (MOR), δ (DOR), κ (KOR), and nociceptin/orphanin FQ (NOP) receptors, play a crucial role in pain relief and are the targets for opioids, both naturally occurring and synthetically created peptides used in pain management.[1] These receptors transmit signals via Gi/o proteins.[1] The MOR is particularly significant as the primary target for analgesics in treating acute and severe pain.[1] However, the analgesic effects of opioid agonists are often accompanied by severe side effects, such as respiratory depression and addiction.[1] A better understanding of how different opioids act on various aspects of signaling is necessary.[1]
Opioids and Opioid Receptors
The family of opioid receptors is crucial for pain relief, as they are the targets for opioids, naturally occurring or synthetically created peptides used in pain management.[1] The MOR is particularly important, being the main target for analgesics in the treatment of acute and severe pain.[1]
Neuronal Networks and Mechanisms in Opioid Addiction
Opioids are agonists that target the opioid receptors, which are crucial for pain relief.[1] The family consists of four members: the MOR, KOR, DOR, and the NOP receptor, all transmitting their downstream signals via Gi/o proteins.[1] The MOR is the main target for analgesics in the treatment of acute and severe pain.[1] The activation of opioid receptors induces the activation of Gi/o proteins, which leads to the replacement of GDP by GTP at the Gα subunit, inducing a dissociation or rearrangement of the heterotrimeric G proteins.[1] These then transmit further signals, like the inhibition of the adenylate cyclase, inducing a decrease in cAMP levels, or the activation of ion channels.[1]
The Dopaminergic System
Opioids, the agonists targeting these receptors, differ in their chemical structure and also in their mode of action in different aspects of signaling.[1] The family of opioid receptors plays a crucial role in pain relief, as they are the targets for the opioids, peptides that occur naturally or are created semi-synthetically or synthetically and used in pain management.[1]
Opioid Receptors Expression by Dopaminergic Neurons
The dopaminergic system plays a crucial role in reward, motivation, and addiction.[10] Opioids can affect the function of immune cells, including proliferation, maturation, chemotaxis, trafficking, phagocytosis, cytokine, and chemokine receptor expression, cytokine synthesis and secretion.[70]
Activation of opioid receptors induces the activation of Gi/o proteins, which leads to the replacement of GDP by GTP at the Gα subunit, inducing a dissociation or rearrangement of the heterotrimeric G proteins.[1]
Mechanisms of Opioid Receptor Modulation of DA Neuron Function
The MOR is particularly important, being the main target for analgesics in the treatment of acute and severe pain.[1] The family consists of four members, the μ (MOR), kappa (KOR), delta (DOR) opioid receptor, and the nociceptin/orphanin FQ receptor (NOP), all transmitting their downstream signals via Gi/o proteins.[1]
The family of opioid receptors plays a crucial role in pain relief, as they are the targets for the opioids, peptides that occur naturally or are created semi-synthetically or synthetically and used in pain management.[1]
Enkephalinergic Modulation of DA Neuron Intrinsic Excitability
Epigenetic Mechanisms and Targets in Drug Addiction
Opioids and Pain Management in Sport
Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs, play a crucial role in drug addiction.[12] These mechanisms can alter gene expression without changing the DNA sequence, leading to long-lasting changes in neuronal function and behavior.[13] Non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), transfer RNA-related fragments (tRFs), and circular RNAs (circRNAs), are also involved in regulating gene expression and are implicated in addiction.[14]
Opioids are agonists that target the opioid receptors, which are crucial for pain relief.[1] The family consists of four members: the MOR, KOR, DOR, and the NOP receptor, all transmitting their downstream signals via Gi/o proteins.[1]
Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs, play a crucial role in drug addiction.[12] These mechanisms can alter gene expression without changing the DNA sequence, leading to long-lasting changes in neuronal function and behavior.[13]
Upcoming Epigenetic Effectors in Nociception
Upcoming Epigenetic Markers in Doping
Conclusions
Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs, play a crucial role in drug addiction.[12] These mechanisms can alter gene expression without changing the DNA sequence, leading to long-lasting changes in neuronal function and behavior.[13]
Opioid receptors activate, delivering calming, pain-relieving effects.
The family of opioid receptors plays a crucial role in pain relief, as they are the targets for the opioids, peptides that occur naturally or are created semi-synthetically or synthetically and used in pain management.[1] The MOR is particularly important, being the main target for analgesics in the treatment of acute and severe pain.[1]
Authoritative Sources
- Kirchhofer, S.B., Kurz, C., Geier, L. et al. Dynamics of agonist-evoked opioid receptor activation revealed by FRET- and BRET-based opioid receptor conformation sensors. Commun Biol 8, 198 (2025). [Dynamics of agonist-evoked opioid receptor activation revealed by FRET- and BRET-based opioid receptor conformation sensors]↩
- Liu, J.F.; Li, J.X. Drug addiction: A curable mental disorder? Acta Pharmacol. Sin.2018, 39, 1823–1829. [Drug addiction: A curable mental disorder?]↩
- Browne, C.J.; Godino, A.; Salery, M.; Nestler, E.J. Epigenetic Mechanisms of Opioid Addiction. Biol. Psychiatry2020, 87, 22–33. [Epigenetic Mechanisms of Opioid Addiction]↩
- Waddington, C.H. The epigenotype. Int. J. Epidemiol.2012, 41, 10–13. [The epigenotype]↩
- Hombach, S.; Kretz, M. Non-coding RNAs: Classification, Biology and Functioning. Adv. Exp. Med. Biol.2016, 937, 3–17. [Non-coding RNAs: Classification, Biology and Functioning]↩
- Sacerdote P, Limiroli E, Gaspani L. Experimental evidence for immunomodulatory effects of opioids. Adv Exp Med Biol. (2003) 521:106–16.↩
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