scholarly journals Hydrogen Sulfide Inhibits Inflammatory Pain and Enhances the Analgesic Properties of Delta Opioid Receptors

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1977
Author(s):  
Aina Porta ◽  
Laura Rodríguez ◽  
Xue Bai ◽  
Gerard Batallé ◽  
Gerad Roch ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Inflammatory Pain ◽  
Phenyl Isothiocyanate ◽  
Diallyl Disulfide ◽  
Dependent Manner ◽  
Analgesic Effects ◽  
Delta Opioid Receptors ◽  
Apoptotic Pathways ◽  
Δ Opioid Receptor ◽  
Transcription Factor Signaling

Chronic inflammatory pain is present in many pathologies and diminishes the patient’s quality of life. Moreover, most current treatments have a low efficacy and significant side effects. Recent studies demonstrate the analgesic properties of slow-releasing hydrogen sulfide (H2S) donors in animals with osteoarthritis or neuropathic pain, but their effects in inflammatory pain and related pathways are not completely understood. Several treatments potentiate the analgesic actions of δ-opioid receptor (DOR) agonists, but the role of H2S in modulating their effects and expression during inflammatory pain remains untested. In C57BL/6J male mice with inflammatory pain provoked by subplantar injection of complete Freund’s adjuvant, we evaluated: (1) the antiallodynic and antihyperalgesic effects of different doses of two slow-releasing H2S donors, i.e., diallyl disulfide (DADS) and phenyl isothiocyanate (P-ITC) and their mechanism of action; (2) the pain-relieving effects of DOR agonists co-administered with H2S donors; (3) the effects of DADS and P-ITC on the oxidative stress and molecular changes caused by peripheral inflammation. Results demonstrate that both H2S donors inhibited allodynia and hyperalgesia in a dose-dependent manner, potentiated the analgesic effects and expression of DOR, activated the antioxidant system, and reduced the nociceptive and apoptotic pathways. The data further demonstrate the possible participation of potassium channels and the Nrf2 transcription factor signaling pathway in the pain-relieving activities of DADS and P-ITC. This study suggests that the systemic administration of DADS and P-ITC and local application of DOR agonists in combination with slow-releasing H2S donors are two new strategies for the treatment of inflammatory pain.

Chemokine CXCL1 in serum mediates the antinociceptive effect of manual acupuncture at ST36

2021 ◽  
pp. 096452842199743
Author(s):  
Shou-Hai Hong ◽  
Sha-Sha Ding ◽  
Yuan Xu ◽  
Kuo Zhang ◽  
Xue Zhao ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Antinociceptive Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Manual Acupuncture ◽  
Tail Vein ◽  
Analgesic Effects ◽  
Peripheral Mechanism ◽  
The Right

Background: Inflammatory pain is the most common type of pain encountered clinically. The analgesic effect of acupuncture has been well-documented. Objective: The aim of this study was to investigate the involvement of chemokine CXCL1 in the serum on manual acupuncture (MA)-induced antinociception. Methods: Rats with inflammatory pain of the right hind paw were induced by intraplantar (i.pl.) administration of complete Freund’s adjuvant (CFA). After wards, the CFA-injected rats were treated daily with MA at ST36 from Day 1 to Day 7, and thermal nociceptive thresholds (paw withdrawal latency; PWL) were analyzed. The concentration of CXCL1 in the serum of the rats was measured by enzyme-linked immunosorbent assay (ELISA) after the first and the last MA treatment. Subsequently, the rats were injected with two doses (5 or 10 μg) of recombinant CXCL1 through the tail vein daily from Day 1 to Day 7 or injected with two doses (6.4 or 16 μg) of anti-CXCL1 antibody using the same methods and course at 30 min before MA, and the PWLs were measured again. Finally, naloxone (500 μg, 0.1 mL) was administered by i.pl. injection into the inflamed paw 5 min before the last MA treatment or last injection of recombinant CXCL1. Results: MA significantly increased the PWLs and upregulated the expression of serum CXCL1 in the CFA-injected rats. Without acupuncture, repeated tail vein injection of recombinant CXCL1 showed an analgesic effect on CFA-induced inflammatory pain. Conversely, the neutralization of serum CXCL1 by anti-CXCL1 antibody decreased MA-induced antinociception in a time-dependent manner. Anti-CXCL1 antibody injected just once before the first MA did not affect MA-induced antinociception. The analgesic effects of MA and recombinant CXCL1 were reversed by an i.pl. injection of naloxone. Conclusion: This study indicates MA at ST36 had an analgesic effect on inflammatory pain and found a novel function of CXCL1. Increased serum CXCL1 had an antinociceptive effect on inflammatory pain induced by CFA. CXCL1 in serum appeared to be a key molecule involved in the peripheral mechanism of MA-induced antinociception. The analgesic effect of MA or recombinant CXCL1 on inflammatory pain might be mediated through a peripheral opioid pathway, which needs further investigation.

The K+-evoked release of [3H]acetylcholine from slices of rat globus pallidus: modulation by δ-opioid receptors

1991 ◽  
Vol 69 (3) ◽  
pp. 414-418 ◽  
Author(s):  
Bianca B. Ruzicka ◽  
Khem Jhamandas
Keyword(s):  
Globus Pallidus ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Cholinergic Neurons ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Release Of Acetylcholine ◽  
Δ Opioid Receptor ◽  
Tritium Release

Previous investigations have shown that the activation of δ-opioid receptors depresses the release of acetylcholine (ACh) in the rat caudate putamen. This finding raised the possibility that the release of ACh is similarly modulated in the globus pallidus, a region containing a distinct population of cholinergic neurons and enriched in enkephalinergic nerve terminals. In the present study the pallidal release of ACh was characterized and the effects of δ-opioid receptor activation on this release were examined. The results show that this release is stimulated by high K+ in a concentration- and Ca2+-dependent manner. D-Pen2,L-Pen5-enkephalin (0.1 – 10 μM), a selective δ-opioid receptor agonist, produced a dose-related inhibition of the 25 mM K+-evoked tritium release. The maximal inhibitory effect, representing a 34% decrease in the K+-induced tritium release, was observed at a concentration of 1 μM. This opioid effect was attenuated by the selective δ-opioid receptor antagonist, ICI 174864 (1 μM). These findings support the role of a δ-opioid receptor in the modulation of ACh release in the rat globus pallidus.Key words: globus pallidus, acetylcholine, enkephalin, release.

scholarly journals Erk is involved in the differentiation induced by diallyl disulfide in the human gastric cancer cell line MGC803

2006 ◽  
Vol 11 (3) ◽  
Author(s):  
Hui Ling ◽  
Liang-Yun Zhang ◽  
Qi Su ◽  
Ying Song ◽  
Zhao-Yang Luo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Specific Activity ◽  
Lucifer Yellow ◽  
Gastric Cancer Cell Line ◽  
Major Constituent ◽  
Diallyl Disulfide ◽  
Human Gastric Cancer ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Induced Differentiation

AbstractDiallyl disulfide (DADS) is a major constituent of garlic. Previously, we found that DADS both inhibited proliferation in human gastric cancer cells in vitro and in vivo, and induced G2/M arrest. In this study, we investigated whether this differentiation effect was induced by DADS in human gastric cancer MGC803 cells, and whether it was related to an alteration in ERK activity. The results showed that the growth of MGC803 cells was inhibited by DADS. Cells treated with DADS displayed a lower nucleocytoplasmic ratio and tended to form gland and intercellular conjunction structures. The ConA-mediated cell agglutination ratio and cells’ ALP specific activity decreased. In MGC803 cells, dye transfer was limited to a few cells neighbouring the dye-injected cell and to a depth of 1–2 layers beneath the scrape site. However, after treatment with DADS, the LY (Lucifer Yellow) was transferred to several cells immediately neighbouring the microinjected cell and to a depth of 2–4 cell layers from the scrape site. This indicated that DADS induced differentiation in MGC803 cells. Western blot analysis revealed that although DADS did not influence the quantity of ERK1/2 protein expressed, it did decrease its phosphorylation in a concentration-dependent manner, compared with the controls. At 30 mg·L−1, DADS inhibited the activation of ERK1/2 in 15–30 min. These results suggested that the DADS-induced differentiation of MGC803 cells involved an alteration of the ERK1/2 signaling pathway.

scholarly journals The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain

1999 ◽  
Vol 57 (3B) ◽  
pp. 753-760 ◽  
Author(s):  
TEREZINHA DE JESUS T. SANTOS ◽  
CARLOS M. DE CASTRO-COSTA ◽  
SÍLVIO D. A. GIFFONI ◽  
FRANKLIN J. C. SANTOS ◽  
RODRIGO S. N. RAMOS ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Aminobutyric Acid ◽  
Thermal Stimulus ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Analgesic Effects ◽  
Nociceptive Stimulus ◽  
Dose Dependent

Baclofen (beta-p-chlorophenyl-GABA) has been used in humans to treat spasticity, as well as trigeminal neuralgia. Since GABA (gamma-aminobutyric acid) has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988), taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p < 0.05) of scratching behaviour and significant increase (p < 0.05) of the latency to the nociceptive thermal stimulus. The absence of antagonism of naloxone suggested a non-participation of an opioid-mediated mechanism in this analgesic effect of baclofen on experimental neuropathic pain.

scholarly journals Hydrogen Sulfide Signaling Axis as a Target for Prostate Cancer Therapeutics

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Mingzhe Liu ◽  
Lingyun Wu ◽  
Sabine Montaut ◽  
Guangdong Yang
Keyword(s):  
Prostate Cancer ◽  
Hydrogen Sulfide ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Cancer Therapeutics ◽  
The Body ◽  
Health Concern ◽  
Diallyl Disulfide ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells

Hydrogen sulfide (H2S) was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important gasotransmitter with various physiological and pathophysiological roles in the body. H2S can be generated endogenously from L-cysteine by multiple enzymes, including cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase. Prostate cancer is a major health concern and no effective treatment for prostate cancers is available. H2S has been shown to inhibit cell survival of androgen-independent, androgen-dependent, and antiandrogen-resistant prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including sulfide salts, diallyl disulfide, diallyl trisulfide, sulforaphane, and other polysulfides, also have been shown to inhibit prostate cancer growth and metastasis. The expression of H2S-producing enzyme was reduced in both human prostate cancer tissues and prostate cancer cells. Androgen receptor (AR) signaling is indispensable for the development of castration resistant prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in prostate cancer and described the molecular alterations, which may bring this gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for prostate cancer.

scholarly journals Chronic inflammatory pain drives alcohol drinking in a sex-dependent manner for C57BL/6J mice

Alcohol ◽  
2019 ◽  
Vol 77 ◽  
pp. 135-145 ◽  
Author(s):  
Waylin Yu ◽  
Lara S. Hwa ◽  
Viren H. Makhijani ◽  
Joyce Besheer ◽  
Thomas L. Kash
Keyword(s):  
Alcohol Drinking ◽  
Inflammatory Pain ◽  
Dependent Manner ◽  
Chronic Inflammatory Pain

Hydrogen Sulfide Reduces Renal Ischemia-Reperfusion Injury by Enhancing Autophagy and Reducing Oxidative Stress

2021 ◽  
Author(s):  
Hui Li ◽  
Shuaiwei Wang ◽  
Shuangshuang An ◽  
Biao Gao ◽  
Tieshan Teng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Beclin 1 ◽  
Dependent Manner ◽  
Protein Levels ◽  
Renal Ischemia Reperfusion Injury

Abstract Background Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury. Hydrogen sulfide (H2S) exerts a protective effect in renal IRI. The present study was carried out to investigate the effects of exogenous H2S on renal IRI by regulating autophagy in mice. Methods Mice were randomly assigned to control, IRI, and NaHS (28, 56 and 100 µmol/kg) groups. Renal IRI was induced by clamping the bilateral renal pedicles for with non-traumatic arterial clamp for 45 min and then reperfused for 24 h. Mice were administered intraperitoneally with NaHS 20 min prior to renal ischemia. Sham group mice underwent the same procedures without clamping. Serum and kidney tissues were harvested 24 h after reperfusion for functional, histological, oxidative stress, and autophagic determination. Results Compared with the control group, the concentrations of serum creatinine (Scr), blood urea nitrogen (BUN), and malondialdehyde (MDA), the protein levels of LC3II/I, Beclin-1, and P62, as well as the number of autophagosomes were significantly increased, but the activity of superoxide dismutase (SOD) was decreased after renal IRI. NaHS pretreatment dramatically attenuated renal IRI-induced renal dysfunction, histological changes, MDA concentration, and p62 expression in a dose-dependent manner. However, NaHS increased the SOD activity and the protein levels of LC3II/I and Beclin-1. Conclusions These results indicate that exogenous H2S protects the kidney from IRI through enhancement of autophagy and reduction of oxidative stress. Novel H2S donors could be developed in the treatment of renal IRI.

scholarly journals Endosomal signaling of delta opioid receptors is an endogenous mechanism and therapeutic target for relief from inflammatory pain

2020 ◽  
Vol 117 (26) ◽  
pp. 15281-15292 ◽  
Author(s):  
Nestor N. Jimenez-Vargas ◽  
Jing Gong ◽  
Matthew J. Wisdom ◽  
Dane D. Jensen ◽  
Rocco Latorre ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Opioid Receptors ◽  
Therapeutic Target ◽  
Inflammatory Pain ◽  
Endogenous Opioids ◽  
Nanoparticle Delivery ◽  
Delta Opioid Receptors ◽  
Extracellular Signal ◽  
Early Endosomes ◽  
Endosomal Signaling

Whether G protein-coupled receptors signal from endosomes to control important pathophysiological processes and are therapeutic targets is uncertain. We report that opioids from the inflamed colon activate δ-opioid receptors (DOPr) in endosomes of nociceptors. Biopsy samples of inflamed colonic mucosa from patients and mice with colitis released opioids that activated DOPr on nociceptors to cause a sustained decrease in excitability. DOPr agonists inhibited mechanically sensitive colonic nociceptors. DOPr endocytosis and endosomal signaling by protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) pathways mediated the sustained inhibitory actions of endogenous opioids and DOPr agonists. DOPr agonists stimulated the recruitment of Gαi/oand β-arrestin1/2 to endosomes. Analysis of compartmentalized signaling revealed a requirement of DOPr endocytosis for activation of PKC at the plasma membrane and in the cytosol and ERK in the nucleus. We explored a nanoparticle delivery strategy to evaluate whether endosomal DOPr might be a therapeutic target for pain. The DOPr agonist DADLE was coupled to a liposome shell for targeting DOPr-positive nociceptors and incorporated into a mesoporous silica core for release in the acidic and reducing endosomal environment. Nanoparticles activated DOPr at the plasma membrane, were preferentially endocytosed by DOPr-expressing cells, and were delivered to DOPr-positive early endosomes. Nanoparticles caused a long-lasting activation of DOPr in endosomes, which provided sustained inhibition of nociceptor excitability and relief from inflammatory pain. Conversely, nanoparticles containing a DOPr antagonist abolished the sustained inhibitory effects of DADLE. Thus, DOPr in endosomes is an endogenous mechanism and a therapeutic target for relief from chronic inflammatory pain.

scholarly journals Triterpenoid Saponin AG8 from Ardisia gigantifolia stapf. Induces Triple Negative Breast Cancer Cells Apoptosis through Oxidative Stress Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Li-Hua Mu ◽  
Li-Hua Wang ◽  
Teng-Fei Yu ◽  
Yu-Ning Wang ◽  
Hong Yan ◽  
...  
Keyword(s):  
Triple Negative ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Ros Generation ◽  
Triterpenoid Saponin ◽  
Dependent Manner ◽  
Breast Cancers ◽  
Underlying Mechanisms ◽  
Apoptotic Pathways ◽  
Dose Dependent

Triple-negative breast cancers (TNBCs) are associated with poor patient survival because of the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expressions. Our previous studies have shown that the triterpenoid saponin AG8 from Ardisia gigantifolia stapf. inhibits the proliferation of MDA-MB-231 cells. In this study, the effects of AG8 were further analyzed in different TNBC cell types: MDA-MB-231, BT-549, and MDA-MB-157 cells. AG8 inhibited the viability of MDA-MB-231, BT-549, and MDA-MB-157 cells in a dose-dependent manner and showed stronger cytotoxicity to African American (AA) and mesenchymal (M) subtypes than Caucasian (CA) and mesenchymal stem-like (MSL) subtypes, respectively. AG8 impaired the uptake of MitoTracker Red CMXRos by the mitochondria of TNBC cells in a dose-dependent manner, and this was recovered by N-acetyl-l-cysteine (NAC). AG8 affected GSH, SOD, and MDA levels of TNBC cells, but different TNBC subtypes had different sensitivities to AG8 and NAC. In addition, we found that AG8 increased the Bax/Bcl-2 ratio and the levels of cytoplasmic cytochrome c and significantly decreased phosphorylation of ERK and AKT in BT549 and MDA-MB-157 cells. AG8 elicited its anticancer effects through ROS generation, ERK and AKT activation, and by triggering mitochondrial apoptotic pathways in TNBC cells. AG8 had selective cytotoxic effects against the AA and M TNBC subtypes and markedly induced MDA-MB-157 (AA subtype) cell apoptosis through pathways that were not associated with ROS, which was different from the other two subtypes. The underlying mechanisms should be further investigated.

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