scholarly journals Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Baomin Dou ◽  
Yanan Li ◽  
Jie Ma ◽  
Zhifang Xu ◽  
Wen Fan ◽  
...  
Keyword(s):  
Glial Cells ◽  
Immune Cells ◽  
Inflammatory Pain ◽  
Tissue Injury ◽  
Nerve Endings ◽  
System Level ◽  
Inflammatory Factors ◽  
Peripheral Sensitization ◽  
Analgesic Effects ◽  
Anti Inflammatory

Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals NLRP3 Inflammasome and IL-33: Novel Players in Sterile Liver Inflammation

2018 ◽  
Vol 19 (9) ◽  
pp. 2732 ◽  
Author(s):  
Katrin Neumann ◽  
Birgit Schiller ◽  
Gisa Tiegs
Keyword(s):  
Immune System ◽  
Liver Disease ◽  
Immune Cells ◽  
Nlrp3 Inflammasome ◽  
Tissue Injury ◽  
Therapeutic Strategies ◽  
Liver Inflammation ◽  
Danger Signal ◽  
Danger Signals ◽  
Anti Inflammatory

In sterile liver inflammation, danger signals are released in response to tissue injury to alert the immune system; e.g., by activation of the NLRP3 inflammasome. Recently, IL-33 has been identified as a novel type of danger signal or “alarmin”, which is released from damaged and necrotic cells. IL-33 is a pleiotropic cytokine that targets a broad range of immune cells and exhibits pro- and anti-inflammatory properties dependent on the disease. This review summarizes the immunomodulatory roles of the NLRP3 inflammasome and IL-33 in sterile liver inflammation and highlights potential therapeutic strategies targeting these pathways in liver disease.

scholarly journals Acupoint nanocomposite hydrogel for simulation of acupuncture and targeted delivery of triptolide against rheumatoid arthritis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shujing Ren ◽  
Heng Liu ◽  
Xitong Wang ◽  
Jiquan Bi ◽  
Shengfeng Lu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Targeted Delivery ◽  
Bone Erosion ◽  
Treg Cells ◽  
Modern Medicine ◽  
Inflammatory Factors ◽  
Nanocomposite Hydrogel ◽  
Analgesic Effects ◽  
Anti Inflammatory

Abstract Background Attenuating inflammatory response and relieving pain are two therapeutic therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with practical targeting ability and other complementary strategies urgently need to be explored. To achieve this goal, an acupoint drug delivery system that can target deliver anti-inflammatory drugs and simulate acupuncture in relieving pain was constructed, which can co-deliver triptolide (TP) and 2-chloro-N (6)-cyclopentyl adenosine (CCPA). Results We have successfully demonstrated that acupoint nanocomposite hydrogel composed of TP-Human serum album nanoparticles (TP@HSA NPs) and CCPA could effectively treat RA. The result shows that CCPA-Gel can enhance analgesic effects specifically at the acupoint, while the mechanical and thermal pain threshold was 4.9 and 1.6 times compared with non-acupoint, respectively, and the nanocomposite gel further enhanced. Otherwise, the combination of acupoint and nanocomposite hydrogel exerted synergetic improvement of inflammation, bone erosion, and reduction of systemic toxicity. Furthermore, it could regulate inflammatory factors and restore the balance of Th17/Treg cells, which provided a novel and effective treatment strategy for RA. Interestingly, acupoint administration could improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48 h), which may explain the better therapeutic efficiency and low toxicity. Conclusion This novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine. Graphical Abstract

scholarly journals Enteric glial cells favour accumulation of anti-inflammatory macrophages during the resolution of muscularis inflammation

2021 ◽  
Author(s):  
Michelle Stakenborg ◽  
Saeed Abdurahiman ◽  
Veronica De Simone ◽  
Gera Goverse ◽  
Nathalie Stakenborg ◽  
...  
Keyword(s):  
Glial Cells ◽  
Intestinal Inflammation ◽  
Mononuclear Phagocyte ◽  
Inflammatory Factors ◽  
Monocyte Differentiation ◽  
Enteric Glial Cells ◽  
Monocyte Recruitment ◽  
Microenvironmental Factors ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Objective: Monocyte-derived macrophages (Mϕs) are crucial regulators during muscularis inflammation. However, it is unclear which microenvironmental factors are responsible for monocyte recruitment and neurotrophic Mϕ differentiation in this paradigm. Here, we investigate Mϕ heterogeneity at different stages of muscularis inflammation and determine how environmental cues can attract and activate tissue protective Mϕs. Design: Single cell RNA sequencing was performed on immune cells from the muscularis of wild-type and CCR2-/- mice at different timepoints after muscularis inflammation. CX3CR1GFP/+ and CX3CR1CreERT2 R26YFP mice were analyzed by flow cytometry and immunofluorescence. The transcriptome of enteric glial cells (EGCs) was investigated using PLPCreERT2 Rpl22HA mice. In addition, we assessed the effect of supernatant from neurosphere-derived EGCs on monocyte differentiation based on the expression of pro- and anti-inflammatory factors. Results: Muscularis inflammation induced marked alterations in mononuclear phagocyte populations associated with a rapid infiltration of Ly6c+ monocytes that locally acquired unique transcriptional states. Trajectory inference analysis revealed two main pro-resolving Mϕs subpopulations during the resolution of muscularis inflammation, i.e. Cd206+ MhcIIhi and Timp2+ MhcIIlo Mϕs, which were both derived from CCR2+ monocytes. Interestingly, we found that EGCs were able to sense damage to the muscularis to stimulate monocyte recruitment and differentiation towards pro-resolving Mϕs via CCL2 and CSF1, respectively. Conclusion: Our study provides a comprehensive insight into pro-resolving Mϕ differentiation and their regulators during muscularis inflammation. We deepened our understanding in the interaction between EGCs and Mϕs, thereby highlighting pro-resolving Mϕ differentiation as a potential novel therapeutic strategy for the treatment of intestinal inflammation.

scholarly journals Targeted Nanoparticles that Mimic Immune Cells in Pain Control Inducing Analgesic and Anti-inflammatory Actions: A Potential Novel Treatment of Acute and Chronic Pain Conditions

2013 ◽  
Vol 3;16 (3;5) ◽  
pp. E199-E216 ◽  
Author(s):  
Susan Hua
Keyword(s):  
Chronic Pain ◽  
Immune Cells ◽  
Inflammatory Pain ◽  
Pain Control ◽  
Time Course ◽  
Intraplantar Injection ◽  
Tail Vein ◽  
Targeted Nanoparticles ◽  
Tail Vein Injection ◽  
Anti Inflammatory

Background: The peripheral immune-derived opioid analgesic pathway has been well established as a novel target in the clinical pain management of a number of painful pathologies, including acute inflammatory pain, neuropathic pain, and rheumatoid arthritis. Objective: Our objective was to engineer targeted nanoparticles that mimic immune cells in peripheral pain control to deliver opioids, in particular loperamide HCl, specifically to peripheral opioid receptors to induce analgesic and anti-inflammatory actions for use in painful inflammatory conditions. This peripheral analgesic system is devoid of central opioid mediated side effects (e.g., respiratory depression, sedation, dependence, tolerance). Study Design: A randomized, double blind, controlled animal trial. Methods: Thirty-six adult male Wistar rats (200 - 250 g) were randomly divided into 6 groups: loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, naloxone methiodide + loperamide HCl-encapsulated antiICAM-1 immunoliposomes, loperamide HCl-encapsulated liposomes, empty anti-ICAM-1 immunoliposomes, empty liposomes, and loperamide solution. Animals received an intraplantar injection of 150 µL Complete Freund’s Adjuvant (CFA) into the right hindpaw and experiments were performed 5 days post-CFA injection, which corresponded to the peak inflammatory response. All formulations were administered intravenously via tail vein injection. The dose administered was 200 µL, which equated to 0.8 mg of loperamide HCl for the loperamide HCl treatment groups (sub-therapeutic dose). Naloxone methiodide (1 mg/kg) was administered via intraplantar injection, 15 minutes prior to loperamide-encapsulated anti-ICAM-1 immunoliposomes. An investigator blinded to the treatment administered assessed the time course of the antinociceptive and antiinflammatory effects using a paw pressure analgesiometer and plethysmometer, respectively. Biodistribution studies were performed 5 days post-CFA injection with anti-ICAM-1 immunoliposomes and control liposomes via tail vein injection using liquid scintillation counting (LSC). Results: Administration of liposomes loaded with loperamide HCl, and conjugated with antibody to intercellular adhesion molecule-1 (anti-ICAM-1), exerted analgesic and anti-inflammatory effects exclusively in peripheral painful inflamed tissue. These targeted nanoparticles produced highly significant analgesic and anti-inflammatory effects over the 48 hour time course studied following intravenous administration in rats with Complete Freund’s Adjuvant-induced inflammation of the paw. All control groups showed no significant antinociceptive or anti-inflammatory effects. Our biodistribution study demonstrated specific localization of the targeted nanoparticles to peripheral inflammatory tissue and no significant uptake into the brain. Limitations: In vivo studies were performed in the well-established rodent model of acute inflammatory pain. We are currently studying this approach in chronic pain models known to have clinical activation of the peripheral immune-derived opioid response. Conclusions: The study presents a novel approach of opioid delivery specifically to injured tissues for pain control. The study also highlights a novel anti-inflammatory role for peripheral opioid targeting, which is of clinical relevance. The potential also exists for the modification of these targeted nanoparticles with other therapeutic compounds for use in other painful conditions. Key words: Pain, inflammation; immune cells, opioids, ICAM-1, loperamide, targeted drug delivery, immunoliposomes

scholarly journals γδ T cells do not contribute to peripheral inflammatory pain

2018 ◽  
Author(s):  
Jelena Petrović ◽  
Jaqueline Raymondi Silva ◽  
Julia P. Segal ◽  
Abigail S. Marshall ◽  
Cortney M. Haird ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Inflammatory Pain ◽  
Tissue Injury ◽  
Γδ T Cells ◽  
Intraplantar Injection ◽  
Baseline Sensitivity ◽  
Peripheral Tissues ◽  
Transgenic Mouse Line ◽  
Thermal Hypersensitivity

AbstractCirculating immune cells, which are recruited to the site of injury/disease, secrete various inflammatory mediators that are critical to nociception and pain. The role of tissue-resident immune cells, however, remains poorly characterized. One of the first cells to be activated in peripheral tissues following injury are γδ T cells, which serve important roles in infection and disease. Using a transgenic mouse line lacking these cells, we sought to identify their contribution to inflammatory pain. Three distinct models of inflammatory pain were used: intraplantar injection of formalin and incisional wound (as models of acute inflammatory pain) and intraplantar injection of complete Freund’s adjuvant (as a model of chronic inflammatory pain). Our results show that absence of these cells does not alter baseline sensitivity, nor does it result in changes to mechanical or thermal hypersensitivity after tissue injury. These results were consistent in both male and female mice, suggesting that there are no sex differences in these outcomes. This comprehensive characterization suggests that γδ T cells do not contribute to basal sensitivity or the development and maintenance of inflammatory pain.

scholarly journals Acupoint Nanocomposite Hydrogel for Simulation of Acupuncture and Targeted Delivery of Triptolide Against Rheumatoid Arthritis

2021 ◽  
Author(s):  
Shujing Ren ◽  
Heng Liu ◽  
Xitong Wang ◽  
Jiquan Bi ◽  
Shengfeng Lu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Targeted Delivery ◽  
Pain Threshold ◽  
Modern Medicine ◽  
Inflammatory Factors ◽  
Nanocomposite Hydrogel ◽  
Analgesic Effects ◽  
Anti Inflammatory ◽  
Targeting Ability

Abstract BackgroundAttenuating the inflammatory response and relieving pain are two therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with effective targeting ability and other complementary strategies are on urgent need to be explored. To achieve this goal, an acupoint drug delivery system that can simulate acupuncture in relieving pain and targeted deliver anti-inflammatory drugs is constructed, which can co-deliver 2-chloro-N (6)-cyclopentyl adenosine (CCPA) and triptolide (TP). ResultsWe have successfully demonstrated that the nanocomposite hydrogel composed of TP-Human serum album nanoparticles (HSA NPs) and CCPA could effectively treat the RA. We found that this combination therapy can enhance analgesic effects while the mechanical pain threshold was 5.2 times compared with model group, and the thermal pain threshold was 1.4 times. Acupoint nanocomposite hydrogel could not only improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48h), but also cooperate with nanomedicine to exert synergetic improvement of inflammation and reduction of systemic toxicity. Furthermore, it can regulate inflammatory factors and restore the balance of Th17/Treg cell which provide a novel effective treatment strategy for RA.ConclusionThis novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine.

Macrophages in Kidney Injury, Inflammation, and Fibrosis

Physiology ◽  
2015 ◽  
Vol 30 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Qi Cao ◽  
David C. H. Harris ◽  
Yiping Wang
Keyword(s):  
Kidney Disease ◽  
Tissue Injury ◽  
Kidney Diseases ◽  
Treatment Options ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Anti Inflammatory ◽  
Molecular Patterns ◽  
Inflammatory Macrophages

Macrophages are found in normal kidney and in increased numbers in diseased kidney, where they act as key players in renal injury, inflammation, and fibrosis. Macrophages are highly heterogeneous cells and exhibit distinct phenotypic and functional characteristics in response to various stimuli in the local microenvironment in different types of kidney disease. In kidney tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce pro-inflammatory macrophages, which contribute to further tissue injury, inflammation, and subsequent fibrosis. Apoptotic cells and anti-inflammatory factors in post-inflammatory tissues induced anti-inflammatory macrophages, which can mediate kidney repair and regeneration. This review summarizes the role of macrophages with different phenotypes in kidney injury, inflammation, and fibrosis in various acute and chronic kidney diseases. Understanding alterations of kidney microenvironment and the factors that control the phenotype and functions of macrophages may offer an avenue for the development of new cellular and cytokine/growth factor-based therapies as alternative treatment options for patients with kidney disease.

scholarly journals Dimethyl itaconate attenuates CFA-induced inflammatory pain via NLRP3/ IL-1β signaling pathway

2021 ◽  
Author(s):  
Jiaqi Lin ◽  
Jinxuan Ren ◽  
Bin Zhu ◽  
Yi Dai ◽  
Dave Schwinn Gao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Inflammatory Factors ◽  
Vehicle Group ◽  
Inflammatory Factor ◽  
Anti Inflammatory ◽  
Dimethyl Itaconate

Abstract Background Itaconate plays potent anti-inflammatory effects and has gradually been discovered as a promising drug candidate for treating inflammatory diseases. However, its roles and underlying mechanism on pain remain unknown. Methods In the current work, we investigated the effects and mechanisms of dimethyl itaconate (DI, a derivative of itaconate) in a mouse model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Male/Female C57 BL/6 mice were randomly divided into five groups: a vehicle group, an CFA group ,an CFA+PBS group and an CFA + DI(10mg /d and 20 mg/d) group.DI was performed for 11 consecutive days after CFA models were established.Paw withdrawal frequencies and paw withdrawal latencies were used to Behavioral Tests. The activation of macrophages and microglia, the level of proinflammatory cytokine production, the number of M1/M2 macrophages were evaluated .The possible involvement of the NLRP3/ IL-1β signaling pathway was also investigated. Results DI significantly reduced mechanical allodynia and thermal hyperalgesia, decreased peripheral inflammatory cell infiltration and the expression of pro-inflammatory factors IL-1β and TNF-α, and upregulated anti-inflammatory factor IL-10. Interestingly, DI promoted macrophages at the inflammatory site polarization from M1 into M2 type. Additionally, DI inhibited activation of macrophages in dorsal root ganglion (DRG) and microglia in the spinal cord, exhibiting reduced expressions of pro-inflammatory cytokines. Mechanismly, DI exerts the analgesic action primarily via inhibiting the activation of NLRP3 inflammasome complex and the release of IL-1β in derived and resident macrophages in the hind paw, DRG and spinal cord. Conclusion DI could alleviate the pain-like behavior of CFA mice by inhibiting the infiltration of plantar inflammatory cells and macrophages activation in DRG and microglia in the spinal cord. The analgesic behavior of itaconate was related to the inhibition of NLRP3 inflammasome. This study suggested possible evidence for prospective itaconate utilization in the management of inflammatory pain for the first time.

scholarly journals Duhaldea pterocaula (Franch.) Anderb. Attenuates Nociception and Inflammation via GABAA Receptors

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunli Huang ◽  
Changsheng Dong ◽  
Yanan Zhu ◽  
Yang Yu ◽  
Huizi Jin ◽  
...  
Keyword(s):  
Mouse Models ◽  
Gabaa Receptors ◽  
Inflammatory Pain ◽  
Therapeutic Agent ◽  
Biological Activities ◽  
Folk Medicine ◽  
Underlying Mechanism ◽  
Pharmacological Effects ◽  
Analgesic Effects ◽  
Anti Inflammatory

Duhaldea pterocaula (Franch.) Anderb, also known as Inula pterocaula Franch (I. pterocaula), is a folk medicine of the Yi nationality in China. The Inula plants display various biological activities, including anti-nociceptive and anti-inflammatory properties. I. pterocaula has been traditionally used for the treatment of bronchitis, vasculitis, and dizziness. However, very few studies have been reported on the pharmacology of I. pterocaula. The present study aims to characterize the anti-nociceptive and anti-inflammatory properties of I. pterocaula and explore the underlying mechanism. I. pterocaula was extracted by 95% ethanol and further portioned with petroleum ether, ethyl acetate (EA) and n-butanol, sequentially, to obtain corresponding factions with different polarities. The EA fraction (IPEA) was found to be one of the most effective fractions. It demonstrated potent analgesic effects in both acute and inflammatory pain mouse models, and caused no anti-nociceptive tolerance. Furthermore, IPEA improved the tolerance of mice to morphine. IPEA also showed potent anti-inflammatory effects on LPS-induced septic mice. BIC, a GABAAR antagonist, reversed the effects of IPEA in pain and inflammation models. Collectively, GABAARs play a key role in the pharmacological effects of IPEA. I. pterocaula may be useful as a complementary or alternative therapeutic agent for the treatment of pain and inflammation.

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