Pharmacological Modulation of Endogenous Opioid Activity to Attenuate Neuropathic Pain in Rats

Liu, Nai-Jiang; Storman, Emiliya M.; Gintzler, Alan R.

doi:10.1016/j.jpain.2018.10.003

Cited by 8 publications

(4 citation statements)

References 73 publications

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“…Additionally, in diestrus where E2 levels are low, mERα-mediated activation of mGluR1 suppressed spinal endomorphin 2 antinociception. However, in proestrus, which E2 levels are high, spinal endomorphin 2 antinociception was facilitated independently of mERα, namely, through glutamate-activated mGluR1 (Liu et al, 2019). Altogether, these findings underscore the significance of the interaction between mER and glutamate receptors in the regulation of neuronal activity and emphasize the need for further investigation to delineate their roles in physiological functions and in disease states.…”

Section: Glutamatementioning

confidence: 79%

The impact of estradiol on serotonin, glutamate, and dopamine systems

Bendis,

Zimmerman,

Onisiforou

et al. 2024

Front. Neurosci.

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Estradiol, the most potent and prevalent member of the estrogen class of steroid hormones and is expressed in both sexes. Functioning as a neuroactive steroid, it plays a crucial role in modulating neurotransmitter systems affecting neuronal circuits and brain functions including learning and memory, reward and sexual behaviors. These neurotransmitter systems encompass the serotonergic, dopaminergic, and glutamatergic signaling pathways. Consequently, this review examines the pivotal role of estradiol and its receptors in the regulation of these neurotransmitter systems in the brain. Through a comprehensive analysis of current literature, we investigate the multifaceted effects of estradiol on key neurotransmitter signaling systems, namely serotonin, dopamine, and glutamate. Findings from rodent models illuminate the impact of hormone manipulations, such as gonadectomy, on the regulation of neuronal brain circuits, providing valuable insights into the connection between hormonal fluctuations and neurotransmitter regulation. Estradiol exerts its effects by binding to three estrogen receptors: estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and G protein-coupled receptor (GPER). Thus, this review explores the promising outcomes observed with estradiol and estrogen receptor agonists administration in both gonadectomized and/or genetically knockout rodents, suggesting potential therapeutic avenues. Despite limited human studies on this topic, the findings underscore the significance of translational research in bridging the gap between preclinical findings and clinical applications. This approach offers valuable insights into the complex relationship between estradiol and neurotransmitter systems. The integration of evidence from neurotransmitter systems and receptor-specific effects not only enhances our understanding of the neurobiological basis of physiological brain functioning but also provides a comprehensive framework for the understanding of possible pathophysiological mechanisms resulting to disease states. By unraveling the complexities of estradiol’s impact on neurotransmitter regulation, this review contributes to advancing the field and lays the groundwork for future research aimed at refining understanding of the relationship between estradiol and neuronal circuits as well as their involvement in brain disorders.

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Section: Glutamatementioning

confidence: 79%

The impact of estradiol on serotonin, glutamate, and dopamine systems

Bendis,

Zimmerman,

Onisiforou

et al. 2024

Front. Neurosci.

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“…Related studies have shown that the intrathecal injection of group I mGluRs agonists produces persistent thermal hyperalgesia and mechanical allodynia, as well as observed prolonged spontaneous nociceptive behaviors, which are mainly dependent on the increased release of glutamate in the spinal cord (Lefebvre et al, 2000). In addition to their own activating effects, group I mGluRs also interact with other receptor systems involved in the modulation of pain signaling, such as opioid and TRPV1 channels, thus playing an important role in the chronicity of pain (Jin et al, 2012; Liu et al, 2019). However, compared with group I mGluRs agonists, the application of group II and group III mGluRs agonists did not produce any nociceptive effects, but had a pain‐relieving effect (Acher & Goudet, 2015; Mazzitelli et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The role of ectopic P granules protein 5 homolog (EPG5) in DHPG‐induced pain sensitization in mice

Mei

Yin

Pan

et al. 2023

Journal of Neurochemistry

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Nociplastic pain is a severe health problem, while its mechanisms are still unclear. (R, S)-3,5-Dihydroxyphenylglycine (DHPG) is a group I metabotropic glutamate receptor (mGluR) agonist that can cause central sensitization, which plays a role in nociplastic pain. In this study, after intrathecal injection of 25 nmol DHPG for three consecutive days, whole proteins were extracted from the L 4~6 lumbar spinal cord of mice 2 h after intrathecal administration on the third day for proteomics analysis. Based on the results, 15 down-regulated and 20 up-regulated proteins were identified in mice. Real-time quantitative PCR (RT-qPCR) and western blotting (WB) revealed that the expression of ectopic P granules protein 5 homolog (EPG5) mRNA and protein were significantly up-regulated compared with the control group, which was consistent with the proteomics results. Originally identified in the genetic screening of Caenorhabditis elegans, EPG5 is mainly involved in regulating autophagy in the body, and in our study, it was mainly expressed in spinal neurons, as revealed by immunohistochemistry staining. After the intrathecal injection of 8 μL adeno-associated virus (AAV)-EPG5 short hairpin RNA (shRNA) to knock down spinal EPG5, the hyperalgesia caused by DHPG was relieved. Altogether, these results suggest that EPG5 plays an

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“…Similarly, in diestrus, mERα-mediated activation of mGluR1 suppressed spinal endomorphin 2 antinociception. However, in proestrus, spinal endomorphin 2 antinociception was facilitated independently of mERα, namely, through glutamate-activated mGluR1 [ 128 ].…”

Section: Cognitive Improvements and Painmentioning

confidence: 99%

Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies

Wnuk

Przepiórska

Pietrzak

et al. 2023

IJMS

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Nuclear- and membrane-initiated estrogen signaling cooperate to orchestrate the pleiotropic effects of estrogens. Classical estrogen receptors (ERs) act transcriptionally and govern the vast majority of hormonal effects, whereas membrane ERs (mERs) enable acute modulation of estrogenic signaling and have recently been shown to exert strong neuroprotective capacity without the negative side effects associated with nuclear ER activity. In recent years, GPER1 was the most extensively characterized mER. Despite triggering neuroprotective effects, cognitive improvements, and vascular protective effects and maintaining metabolic homeostasis, GPER1 has become the subject of controversy, particularly due to its participation in tumorigenesis. This is why interest has recently turned toward non-GPER-dependent mERs, namely, mERα and mERβ. According to available data, non-GPER-dependent mERs elicit protective effects against brain damage, synaptic plasticity impairment, memory and cognitive dysfunctions, metabolic imbalance, and vascular insufficiency. We postulate that these properties are emerging platforms for designing new therapeutics that may be used in the treatment of stroke and neurodegenerative diseases. Since mERs have the ability to interfere with noncoding RNAs and to regulate the translational status of brain tissue by affecting histones, non-GPER-dependent mERs appear to be attractive targets for modern pharmacotherapy for nervous system diseases.

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Pharmacological Modulation of Endogenous Opioid Activity to Attenuate Neuropathic Pain in Rats

Cited by 8 publications

References 73 publications

The impact of estradiol on serotonin, glutamate, and dopamine systems

The impact of estradiol on serotonin, glutamate, and dopamine systems

The role of ectopic P granules protein 5 homolog (EPG5) in DHPG‐induced pain sensitization in mice

Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies

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