Endogenous opiates and behavior: 2017

Bodnar, Richard J.

doi:10.1016/j.peptides.2019.170223

Cited by 22 publications

(12 citation statements)

References 1,261 publications

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“…The release of inflammatory factors, notably IL-1β, induces the expression and release of opioids by these cells, which, once attached to the receptors of peripheral nerve fibers, inhibit neuronal triggering and transmitter release [12][13][14][15][16] . The present study demonstrated that supernatant from keratinocyte and fibroblast culture promotes analgesia during inflammatory pain induced by carrageenan in a model of mechanical hyperalgesia, corroborating previous studies [16][17][18][32][33][34] . The data obtained suggest that the opioid receptor seems to be involved in the analgesic effect of keratinocyte culture.…”

Section: Discussionsupporting

confidence: 92%

Considerations about the new concept of pain

Souza¹,

Barros

2020

Brazilian Journal of Pain

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BACKGROUND AND OBJECTIVES:Inflammation is a defense response of the body to a cellular damage caused by physical, chemical or biological agents, which triggers, among other factors, pain. Although inflammation plays an important role in the protection and regeneration of tissue injury, inflammatory pain results in decreased quality of life. In view of this, the development of safe and less invasive forms for the treatment of inflammatory pain is of great importance. The objective of this study was to evaluate the antihyperalgesic potential of the culture supernatant of keratinocytes and human fibroblasts in an experimental model of inflammatory hyperalgesia. METHODS: Evaluation of carrageenan induced inflammatory hyperalgesia through the use of electronic von Frey in animal models treated with culture supernatant of keratinocytes and fibroblasts. RESULTS: Local administration of naloxone, a nonselective opioid antagonist, in peripheral tissue, has been observed to inhibit the antihyperalgesic effect of the keratinocyte culture supernatant. Fibroblast culture supernatant on days 1 and 3 reverses for 2 hours the carrageenan induced inflammatory hyperalgesia, which is mediated by µ opioid agonist. CONCLUSION: This study indicates that culture supernatant of fibroblasts and keratinocytes is capable of inducing antinociception in inflammatory hyperalgesia, mediated by the release of Evaluation of the keratinocytes or fibroblasts culture supernatant in an inflammatory hyperalgesia modelAvaliação do sobrenadante da cultura de queratinócitos ou fibroblastos em modelo de hiperalgesia inflamatória

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Section: Discussionsupporting

confidence: 92%

Considerations about the new concept of pain

Souza¹,

Barros

2020

Brazilian Journal of Pain

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“…Interestingly, while the administration of MOR agonists, such as morphine, fentanyl, and [ d ‐Ala2, N ‐MePhe4, Gly‐ol]‐enkephalin, is highly effective in the treatment of inflammatory pain, they exhibit limited efficacy in the management of neuropathic pain and are associated with numerous side effects, such as sedation, constipation, tolerance, and respiratory depression 124–127 . In contrast, DOR agonists, such as [ d ‐Pen2,5]‐enkephalin hydrate (DPDPE), [ d ‐Ser2, Leu5, Thr6]‐enkephalin (DSLET), (+)‐4‐[(αR)‐α‐((2S,5R)‐4‐Allyl‐2,5‐dimethyl‐1‐piperazinyl)‐3‐methoxybenzyl]‐N,N‐diethylbenzamide, and H‐Dmt‐Tic‐NH–CH(CH 2 –COOH)–Bid (UFP‐512), have lower potencies against inflammatory pain than MOR agonists but inhibit both inflammatory and neuropathic pain with similar efficacy and few side effects 48,77,123,126,128–131 …”

Section: Activation Of Ho‐1 and Carbon Monoxide Modulates The Antinociceptive Effects Of Opioids Cannabinoids And Other Analgesics Duringmentioning

confidence: 99%

The role of carbon monoxide, heme oxygenase 1, and the Nrf2 transcription factor in the modulation of chronic pain and their interactions with opioids and cannabinoids

Pol

2020

Medicinal Research Reviews

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Chronic pain and its associated comorbidities are difficult to treat, even when the most potent analgesic compounds are used. Thus, research on new strategies to effectively relieve nociceptive and/or emotional disorders accompanying chronic pain is essential. Several studies have demonstrated the anti‐inflammatory and antinociceptive effects of different carbon monoxide‐releasing molecules (CO‐RMs), inducible heme oxygenase 1 (HO‐1), and nuclear factor‐2 erythroid factor‐2 (Nrf2) transcription factor activators in several models of acute and chronic pain caused by inflammation, nerve injury or diabetes. More recently, the antidepressant and/or anxiolytic effects of several Nrf2 transcription factor inducers were demonstrated in a model of chronic neuropathic pain. These effects are mainly produced by inhibition of oxidative stress, inflammation, glial activation, mitogen‐activated protein kinases and/or phosphoinositide 3‐kinase/phospho‐protein kinase B phosphorylation in the peripheral and/or central nervous system. Other studies also demonstrated that the analgesic effects of opioids and cannabinoids are improved when these drugs are coadministered with CO‐RMs, HO‐1 or Nrf2 activators in different preclinical pain models and that these improvements are generally mediated by upregulation or prevention of the downregulation of µ‐opioid receptors, δ‐opioid receptors and/or cannabinoid 2 receptors in the setting of chronic pain. We reviewed all these studies as well as studies on the mechanisms of action underlying the effects of CO‐RMs, HO‐1, and Nrf2 activators in chronic pain. In summary, activation of the Nrf2/HO‐1/carbon monoxide signaling pathway alone and/or in combination with the administration of specific analgesics is a valid strategy for the treatment of chronic pain and some associated emotional disorders.

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“…The dopaminergic systems also interact with BDNF and MOR systems, and therefore MOR over-activation by an excess of morphine potentially could compromise the integrative aspects of behavior. According to the FET model, and as commonly reported [16, 25], the MOR activates the release of dopamine, facilitating behavioral integration (speed of actions, ease of putting together a program of actions). Recent animal studies have shown that chronic morphine consumption suppresses the expression of the BDNF gene in the part of the rat brain causing an increase in dopamine release in response to morphine [26].…”

Section: Introductionmentioning

confidence: 93%

Opium Effect in Pregnancy on the Dynamics of Maternal Behavior: Testing a Neurochemical Model

et al. 2021

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Background: Investigations into neurochemical mechanisms of opioid addiction are difficult due to the complexity of behavior and multiplicity of involved neurotransmitter and hormonal systems. The aim of this study was to examine the benefits of structured analysis of these mechanisms using the framework of the neurochemical model Functional Ensemble of Temperament (FET) and the example of maternal behavior under the condition of opium consumption in pregnancy. The FET differentiates between (a) endurance, (b) speed of integration, and (c) emotionality aspects of behavior suggesting that these systems are differentially regulated by (a) serotonin-neuropeptides-brain-derived neurotrophic factor (BDNF), (b) dopamine-GABA, and (c) opioid receptor systems, correspondingly. The FET also suggests that mu-opioid receptors (MORs) binding the endorphines (including opium’s ingredient morphine) have a stronger association with regulation endurance, whereas delta-OR have a stronger association with integration of behavior and kappa-OR – with the perceptual mobilization seen in anxiety. To test the predictions of this model, we compared the impact of massive MOR dysregulation on 3 behavioral aspects of behavior and on serotonin, BDNF, and corticosterone levels. Methods: The study used 24 female white Wistar rats which were randomly divided into (1) control group: pregnant rats without any intervention; (2) opium-exposed group: animals that were exposed to opium during pregnancy and after the delivery until the end of the study. At the end of the study, the levels of BDNF, serotonin (5-HT) in the hippocampus of the mother’s brain, and serum corticosterone, as well as 12 aspects of the maternal behavior were evaluated. The differences between control and experimental groups were assessed using the t test for independent samples. Results: The BDNF and serotonin concentrations in the hippocampus of the mother rats which were exposed to opium were lower than in the control group; the mean corticosterone in exposed mothers was higher than in the control group. Behaviorally, opium-consuming mothers showed lower endurance in 4 distinct behavioral categories (nesting, feeding, grooming, and retrieval) than the mothers in the control group. Ease of integration of behavior was affected to a lesser degree, showing a significant effect only in 1 out of 5 applied measures. Self-grooming, seen as an emotionality-related aspect of behavior, was not affected. Conclusion: Opium exposure during pregnancy in our experiment primarily reduced the endurance of rat’s maternal behavior, but the speed of integration of behavioral acts was less affected. This negative impact of opium on endurance was associated with a decrease of BDNF and serotonin levels in the hippocampus and an increase in corticosterone level in opium-consuming mothers. There is no effect of opium exposure on self-grooming behavior. This pattern supports the FET hypothesis about the role of 5-HT and BDNF in endurance, differential regulation of endurance, integrative and emotionality aspects of behavior, and differential association of the MOR system with endurance aspects, in comparison with kappa- and delta opioid receptors.

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Endogenous opiates and behavior: 2017

Cited by 22 publications

References 1,261 publications

Considerations about the new concept of pain

Considerations about the new concept of pain

The role of carbon monoxide, heme oxygenase 1, and the Nrf2 transcription factor in the modulation of chronic pain and their interactions with opioids and cannabinoids

Opium Effect in Pregnancy on the Dynamics of Maternal Behavior: Testing a Neurochemical Model

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