scholarly journals Simultaneous Inhibition of PGE2and PGI2Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain Models

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ryusuke Sugita ◽  
Harumi Kuwabara ◽  
Kazufumi Kubota ◽  
Kotaro Sugimoto ◽  
Toshihiro Kiho ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Concomitant Administration ◽  
Prostaglandin E ◽  
Compound I ◽  
Synthesis Inhibitor ◽  
Analgesic Effects ◽  
Ep4 Receptor ◽  
Prostacyclin Receptor ◽  
Pain Models

Prostaglandin E2(PGE2) is well known as a mediator of inflammatory symptoms such as fever, arthritis, and inflammatory pain. In the present study, we evaluated the analgesic effect of our selective PGE2synthesis inhibitor, compound I, 2-methyl-2-[cis-4-([1-(6-methyl-3-phenylquinolin-2-yl)piperidin-4-yl]carbonyl amino)cyclohexyl] propanoic acid, in rat yeast-induced acute and adjuvant-induced chronic inflammatory pain models. Although this compound suppressed the synthesis of PGE2selectively, no analgesic effect was shown in both inflammatory pain models. Prostacyclin (PGI2) also plays crucial roles in inflammatory pain, so we evaluated the involvement of PGI2signaling in rat inflammatory pain models using prostacyclin receptor (IP) antagonist, RO3244019. RO3244019 showed no analgesic effect in inflammatory pain models, but concomitant administration of compound I and RO3244019 showed analgesic effects comparable to celecoxib, a specific cyclooxygenase- (COX-) 2 inhibitor. Furthermore, coadministration of PGE2receptor 4 (EP4) antagonist, CJ-023423, and RO3244019 also showed an analgesic effect. These findings suggest that both PGE2signaling, especially through the EP4 receptor, and PGI2signaling play critical roles in inflammatory pain and concurrent inhibition of both signals is important for suppression of inflammatory hyperalgesia.

scholarly journals Antinociceptive Effects of Sinomenine Combined With Ligustrazine or Paracetamol in Animal Models of Incisional and Inflammatory Pain

2021 ◽  
Vol 11 ◽  
Author(s):  
Tianle Gao ◽  
Tao Li ◽  
Wei Jiang ◽  
Weiming Fan ◽  
Xiao-Jun Xu ◽  
...  
Keyword(s):  
Animal Models ◽  
Inflammatory Pain ◽  
Extracellular Fluid ◽  
Postoperative Pain Management ◽  
Assay Method ◽  
Pharmacokinetic Studies ◽  
Analgesic Effects ◽  
Pain Models ◽  
Potential Benefits ◽  
Incisional Pain

The management of postoperative and inflammatory pain has been a pressing challenge in clinical settings. Sinomenine (SN) is a morphinan derived alkaloid with remarkable analgesic properties in various kinds of pain models. The aim of the current study is to investigate if SN can enhance the effect of ligustrazine hydrochloride (LGZ) or paracetamol (PCM) in animal models of postoperative and inflammatory pain. And to determine if the combined therapeutic efficacies can be explained by pharmacokinetics changes. Pharmacological studies were performed using a rat model of incisional pain, and a mouse model of carrageenan induced inflammatory pain. Pharmacokinetic studies were performed using a microdialysis sampling and HPLC-MS/MS assay method to quantify SN, LGZ, and PCM levels in blood and extracellular fluid in brain. We found that SN plus LGZ or SN plus PCM produced marked synergistic analgesic effects. However, such synergy was subjected to pain modalities, and differed among pain models. Pharmacological discoveries could be partially linked to pharmacokinetic alterations in SN combinations. Though further evaluation is needed, our findings advocate the potential benefits of SN plus LGZ for postoperative pain management, and SN plus PCM for controlling 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.

scholarly journals Electroacupuncture Stimulation Alleviates CFA-Induced Inflammatory Pain Via Suppressing P2X3 Expression

2019 ◽  
Vol 20 (13) ◽  
pp. 3248 ◽  
Author(s):  
Xuaner Xiang ◽  
Sisi Wang ◽  
Fangbing Shao ◽  
Junfan Fang ◽  
Yingling Xu ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Purinergic Receptor ◽  
Pathological Process ◽  
Spinal Cord Dorsal Horn ◽  
Chronic Inflammatory Pain ◽  
Withdrawal Threshold ◽  
Analgesic Effects ◽  
Spinal Cord Dorsal

Chronic inflammatory pain is one of the most common complaints that seriously affects patients’ quality of life. Previous studies have demonstrated that the analgesic effect of electroacupuncture (EA) stimulation on inflammatory pain is related to its frequency. In this study, we focused on whether the analgesic effects of EA are related to the period of stimulation. Purinergic receptor P2X3 (P2X3) is involved in the pathological process underlying chronic inflammatory pain and neuropathic pain. We hypothesized that 100 Hz EA stimulation alleviated Freund’s complete adjuvant (CFA) induced inflammatory pain via regulating P2X3 expression in the dorsal root ganglion (DRG) and/or spinal cord dorsal horn (SCDH). We also assumed that the analgesic effect of EA might be related to the period of stimulation. We found that both short-term (three day) and long-term (14 day) 100 Hz EA stimulation effectively increased the paw withdrawal threshold (PWT) and reversed the elevation of P2X3 in the DRG and SCDH of CFA rats. However, the analgesic effects of 100 Hz EA were not dependent on the period of stimulation. Moreover, P2X3 inhibition or activation may contribute to or attenuate the analgesic effects of 100 Hz EA on CFA-induced inflammatory pain. This result indicated that EA reduced pain hypersensitivity through P2X3 modulation.

scholarly journals Analgesic characteristics of a newly developed α2δ ligand, mirogabalin, on inflammatory pain

2021 ◽  
Vol 17 ◽  
pp. 174480692110521
Author(s):  
Shuji Komatsu ◽  
Shingo Nakamura ◽  
Takahiro Nonaka ◽  
Toshihiko Yamada ◽  
Tatsuo Yamamoto
Keyword(s):  
Oral Administration ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Time Course ◽  
Formalin Test ◽  
Formalin Injection ◽  
Intracerebroventricular Administration ◽  
Analgesic Effects ◽  
Adrenergic Antagonist ◽  
Sites Of Action

Mirogabalin is a novel α2δ ligand approved in Japan for the treatment of peripheral neuropathic pain. However, the sites of action of α2δ ligands to produce analgesic effects on inflammatory pain remain unclear. In this study, we investigated the analgesic effect and site of action of mirogabalin using the rat formalin test, an acute inflammatory pain model. Mirogabalin was administered orally, intrathecally, and intracerebroventricularly. Open field tests were performed to evaluate the effect of oral-, intrathecally, and intracerebroventricularly administered mirogabalin on locomotor activity and orientation ability. Oral mirogabalin produced an analgesic effect when the formalin test was performed 4 h, but not 1 or 2 h, after oral administration. Intrathecal, but not intracerebroventricular, administration of mirogabalin produced analgesic effects when mirogabalin was administered 10 min before formalin injection. These analgesic effects were not antagonized by idazoxan, an α2 adrenergic antagonist; WAY100135, a 5-HT1A antagonist; or naloxone, an opioid receptor antagonist. Mirogabalin attenuated moving distances 1 and 2 h after oral administration and 10 min after intracerebroventricular administration, but not 10 min after intrathecal administration. In the oral administration group, the time course of the analgesic effect was different from that of moving distance. In the intracerebroventricular group, mirogabalin attenuated moving distances but did not produce an analgesic effect. In the intrathecal group, mirogabalin produced an analgesic effect but did not affect moving distances. These findings suggest that the analgesic effect of mirogabalin on the rat formalin test is mediated by spinal action and not by the activation of α2, 5-HT1A, or opioid receptors, and that the inhibitory effect of mirogabalin on moving distances is mediated by the supraspinal brain.

scholarly journals Angelica dahurica extracts attenuate CFA-induced inflammatory pain via TRPV1 in mice

2021 ◽  
Author(s):  
Chan Zhu ◽  
Meiyuan Wang ◽  
Jun Guo ◽  
Shu-Lan Su ◽  
Guang Yu ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Ultra Performance Liquid Chromatography ◽  
Transient Receptor Potential Vanilloid ◽  
Angelica Dahurica ◽  
Protein Activity ◽  
Pain Models ◽  
Transient Receptor

Abstract Background: Angelica dahurica, belonging to the family Apiaceae, is a well-known herbal medicine. The roots of Angelica dahurica is commonly used for the treatment of headache, toothache, abscess, furunculosis, and acne. However, little is known about their analgesic molecular mechanism underlying pain relief. Here, we investigated the anti-nociceptive activity of Angelica dahurica extracts（ADE） in complete freund's adjuvant(CFA)-induced inflammatory pain mice models, and its possible mechanism of the action associated with transient receptor potential vanilloid member 1 (TRPV1) was also explored. Material and Methods: In this study, we used behavioral tests to assess the analgesic effect of the ADE on CFA-induced inflammatory pain mice models. TRPV1 protein activity in dorsal root ganglion (DRG) was assessed with calcium imaging assay. TRPV1 expression was detected with western blot and immunohistochemistry. Then we examined the constituents of ADE using combined ultra-performance liquid chromatography-quadrupole time-of-light mass spectrometry (UPLC/Q−TOF−MS).Results: Our results showed that ADE effectively attenuated mechanical and thermal hypersensitivities in CFA-induced inflammatory pain model in mice. ADE also significantly reduced the activity and the protein expression of TRPV1 in DRG from CFA mice. Conclusion: These findings suggest that ADE exhibits an analgesic effect in CFA inflammatory pain models by targeting TRPV1. Therefore, ADE might be an attractive and suitable analgesic agent for the management of chronic inflammatory pain.

Mesenchymal Stem Cells and their Exosomes: Promising Therapeutics for Chronic Pain

2019 ◽  
Vol 14 (8) ◽  
pp. 644-653 ◽  
Author(s):  
Jinxuan Ren ◽  
Na Liu ◽  
Na Sun ◽  
Kehan Zhang ◽  
Lina Yu
Keyword(s):  
Stem Cells ◽  
Chronic Pain ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Side Effects ◽  
Human Life ◽  
Analgesic Effects ◽  
Pain Models ◽  
Inflammatory Drugs ◽  
Anxiety Depression

Chronic pain is a common condition that seriously affects the quality of human life with variable etiology and complicated symptoms; people who suffer from chronic pain may experience anxiety, depression, insomnia, and other harmful emotions. Currently, chronic pain treatments are nonsteroidal anti-inflammatory drugs and opioids; these drugs are demonstrated to be insufficient and cause severe side effects. Therefore, research into new therapeutic strategies for chronic pain is a top priority. In recent years, stem cell transplantation has been demonstrated to be a potent alternative for the treatment of chronic pain. Mesenchymal stem cells (MSCs), a type of pluripotent stem cell, exhibit multi-directional differentiation, promotion of stem cell implantation, and immune regulation; they have also been shown to exert analgesic effects in several chronic pain models. Exosomes produced by MSCs have been demonstrated to relieve painful symptoms with fewer side effects. In this review, we summarize the therapeutic use of MSCs in various chronic pain studies. We also discuss ways to enhance the treatment effect of MSCs. We predict in the future, cell-free therapies for chronic pain will develop from exosomes secreted by MSCs.

scholarly journals New ibuprofen derivatives with thiazolidine-4-one scaffold with improved pharmaco-toxicological profile

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ioana-Mirela Vasincu ◽  
Maria Apotrosoaei ◽  
Sandra Constantin ◽  
Maria Butnaru ◽  
Liliana Vereștiuc ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Visceral Pain ◽  
Biological Effects ◽  
Maximum Effect ◽  
Tail Flick ◽  
Paw Edema ◽  
Cell Viability Assay ◽  
Thermal Nociception ◽  
Analgesic Effects ◽  
Anti Inflammatory

Abstract Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cytotoxicity and toxicity degree on mice, revealed that the ibuprofen derivatives (4a-n) are non-cytotoxic at 2 μg/ml. In addition, ibuprofen derivatives reduced carrageenan-induced paw edema in rats, for most of them the maximum effect was recorded at 4 h after administration which means they have medium action latency, similar to that of ibuprofen. Moreover, for compound 4d the effect was higher than that of ibuprofen, even after 24 h of administration. The analgesic effect evaluation highlighted that 4 h showed increased pain inhibition in reference to ibuprofen in thermal (tail-flick assay) and visceral (writhing assay) nociception models. Conclusions The study revealed for ibuprofen derivatives, noted as 4 m, 4 k, 4e, 4d, a good anti-inflammatory and analgesic effect and also a safer profile compared with ibuprofen. These findings could suggest the promising potential use of them in the treatment of inflammatory pain conditions.

scholarly journals Purinergic ATP triggers moxibustion-induced local anti-nociceptive effect on inflammatory pain model

2021 ◽  
Author(s):  
Hai-Yan Yin ◽  
Ya-Peng Fan ◽  
Juan Liu ◽  
Dao-Tong Li ◽  
Jing Guo ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Intramuscular Injection ◽  
High Performance ◽  
Atp Hydrolysis ◽  
Purinergic Signalling ◽  
Pain Model ◽  
Speed Up

AbstractPurinergic signalling adenosine and its A1 receptors have been demonstrated to get involved in the mechanism of acupuncture (needling therapy) analgesia. However, whether purinergic signalling would be responsible for the local analgesic effect of moxibustion therapy, the predominant member in acupuncture family procedures also could trigger analgesic effect on pain diseases, it still remains unclear. In this study, we applied moxibustion to generate analgesic effect on complete Freund’s adjuvant (CFA)-induced inflammatory pain rats and detected the purine released from moxibustioned-acupoint by high-performance liquid chromatography (HPLC) approach. Intramuscular injection of ARL67156 into the acupoint Zusanli (ST36) to inhibit the breakdown of ATP showed the analgesic effect of moxibustion was increased while intramuscular injection of ATPase to speed up ATP hydrolysis caused a reduced moxibustion-induced analgesia. These data implied that purinergic ATP at the location of ST36 acupoint is a potentially beneficial factor for moxibustion-induced analgesia.

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