scholarly journals Chronic THC vapor rescues inflammation-related thermal hyperalgesia and causes cell type-specific modifications in vlPAG neurons

2021 ◽  
Author(s):  
Leslie K Kelley ◽  
Jason Middleton ◽  
Nicholas W. Gilpin ◽  
Savannah HM Lightfoot ◽  
Matthew N Hill
Keyword(s):  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Suppressive Effect ◽  
Drug Dosage ◽  
Male Rats ◽  
Synaptic Inhibition ◽  
Duration Of Treatment ◽  
Action Potential Firing ◽  
Thermal Nociception ◽  
Chronic Inflammatory Pain

To reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain and/or as a strategy for reducing opioid drug dosage and duration of treatment (i.e., so-called opioid-sparing effects). Previous preclinical work has shown robust anti-hyperalgesic effects of systemic THC and acute anti-hyperalgesic effects of vaporized THC. Here, we used a vapor inhalation model in rats to test chronic THC vapor inhalation effects on thermal nociception and mechanical sensitivity, as well as midbrain (i.e., periaqueductal gray [PAG]) neuronal function, in adult male rats with chronic inflammatory pain. We report that chronic THC vapor inhalation produces a robust anti-hyperalgesic effect in rats with chronic inflammatory pain, and that this effect persists 24 hours after cessation of THC exposure. We demonstrate that chronic THC vapor inhalation also modulates intrinsic and synaptic properties of ventrolateral PAG (vlPAG) neurons, including reductions in action potential firing rate and reductions in spontaneous inhibitory synaptic transmission, and that these effects occur specifically in neurons that respond to current input with a delayed firing phenotype. Finally, we show that the suppressive effect of the bath-applied mu-opioid receptor (MOR) agonist DAMGO on synaptic inhibition in the vlPAG is enhanced in slices taken from rats with a history of chronic THC vapor inhalation. Collectively, these data show that chronic THC vapor inhalation produces lasting attenuation of thermal hyperalgesia and reduces synaptic inhibition in the vlPAG of rats with chronic inflammatory pain.

scholarly journals Analgesic Effect of Moxibustion with Different Temperature on Inflammatory and Neuropathic Pain Mice: A Comparative Study

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Zhou ◽  
Ruxue Lei ◽  
Chuanyi Zuo ◽  
Yunqing Yue ◽  
Qin Luo ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Spared Nerve Injury ◽  
Chronic Neuropathic Pain ◽  
Chronic Inflammatory Pain ◽  
Significant Difference ◽  
Different Temperatures

The aim of this study was to determine whether variation of temperature during moxibustion would generate division of analgesic effect. The moxibustion with different temperatures (37°C, 42°C, 47°C, and 52°C) was applied to ST36 acupoint for 30 minutes in chronic inflammatory or neuropathic pain mice. The analgesic effect was evaluated by thermal hyperalgesia test in chronic inflammatory pain and by mechanical allodynia in neuropathic pain, respectively. The results indicated that interventions of moxibustion with different temperature caused different analgesic effect on either chronic inflammatory induced by injection of complete Freund’s adjuvant (CFA) or neuropathic pain induced by spared nerve injury (SNI). In chronic inflammatory pain, different moxibustion temperature generated different intensity of analgesic effect: the higher the better. In chronic neuropathic pain, stronger analgesic effect was found in moxibustion with temperature 47°C or 52°C other than 37°C and 42°C. However, there is no significant difference displayed between moxibustion temperatures 47°C and 52°C or 37°C and 42°C. It implies that the temperature should be taken into account for moxibustion treatment to chronic inflammatory or neuropathic pain.

Far Infrared Emitted by Bioceramics Reduces Mechanical and Thermal Hyperalgesia in an Animal Model of Chronic Inflammatory Pain

2014 ◽  
Vol 20 (5) ◽  
pp. A33-A33
Author(s):  
Aline A. Emer ◽  
Francisco Jose Cidral-Filho ◽  
Fernanda Madeira ◽  
Bruna L. Turnes ◽  
Daniel F. Martins
Keyword(s):  
Animal Model ◽  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Far Infrared ◽  
Chronic Inflammatory Pain

scholarly journals Effects and Mechanisms of Electroacupuncture on Chronic Inflammatory Pain and Depression Comorbidity in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hung-Yu Huang ◽  
Hsien-Yin Liao ◽  
Yi-Wen Lin
Keyword(s):  
Chronic Pain ◽  
Signaling Pathway ◽  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Chronic Inflammatory Pain ◽  
Calcium Calmodulin Dependent ◽  
Successful Induction ◽  
Dependent Protein ◽  
The Brain ◽  
Depression Disorder

Comorbidity of chronic pain and major depression disorder (MDD) are common diseases. However, the mechanisms of electroacupuncture (EA) and the responses of N-methyl-D-aspartate receptors in the brain remain unclear. Three injections of complete Freund's adjuvant (CFA) were administered to induce chronic inflammatory pain (CIP). EA was then performed once every other day from days 14 to 28. Behavior tests of chronic pain and depression were evaluated to make sure of the successful induction of comorbidity. We used Western blotting to analyze brain tissue from the prefrontal cortex (PFC), hippocampus, and hypothalamus for levels of phosphorylated N-methyl-D-aspartate receptor subunit 1 (pNR1), NR1, pNR2B, NR2B, and calcium/calmodulin-dependent protein kinase type II alpha isoform (pCaMKIIα). The mechanical hyperalgesia, thermal hyperalgesia, and depression were observed in the CIP group. Furthermore, decreased levels of N-methyl-D-aspartate receptors (NMDARs) were also noted. Not Sham EA but EA reversed chronic pain and depression as well as the decreased levels of NMDA in the signaling pathway. The CFA injections successfully induced a significant comorbidity model. EA treated the comorbidity by upregulating the NMDA signaling pathway in the PFC, hippocampus, and hypothalamus. Our results indicated significant mechanisms of comorbidity of chronic pain and MDD and EA-analgesia that involves the regulation of the NMDAR signaling pathway. These findings may be relevant to the evaluation and treatment of comorbidity of chronic pain and MDD.

scholarly journals Reduced GABAergic transmission in the ventrobasal thalamus contributes to thermal hyperalgesia in chronic inflammatory pain

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Chan Zhang ◽  
Rong-Xiang Chen ◽  
Yu Zhang ◽  
Jie Wang ◽  
Feng-Yu Liu ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Patch Clamp Recording ◽  
Gabaergic Transmission ◽  
Chronic Inflammatory Pain ◽  
Whole Cell Patch Clamp ◽  
Ventrobasal Thalamus

Abstract The ventrobasal (VB) thalamus is innervated by GABAergic afferents from the thalamic reticular nucleus (TRN) and participates in nociception. But how the TRN-VB pathway regulates pain is not fully understood. In the present study, we reported decreased extracellular GABA levels in the VB of rats with CFA-induced chronic inflammatory pain, measured by microdialysis with HPLC analysis. In vitro whole-cell patch-clamp recording showed decreased amplitudes of tonic currents, increased frequencies of mIPSCs, and increased paired-pulse ratios in thalamic slices from chronic inflammatory rats (7 days). Microinjection of the GABAAR agonist muscimol and optogenetic activation of the TRN-VB pathway relieved thermal hyperalgesia in chronic inflammatory pain. By contrast, microinjecting the extrasynaptic GABAAR agonist THIP or selective knockout of synaptic GABAAR γ2 subunits aggravated thermal hyperalgesia in the chronic stage of inflammatory pain. Our findings indicate that reduced GABAergic transmission in the VB contributes to thermal hyperalgesia in chronic inflammatory pain, which could be a synaptic target for pharmacotherapy.

scholarly journals Role of Transient Receptor Potential Vanilloid 1 in Electroacupuncture Analgesia on Chronic Inflammatory Pain in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Yang ◽  
Ching-Liang Hsieh ◽  
Yi-Wen Lin
Keyword(s):  
Inflammatory Pain ◽  
Transient Receptor Potential ◽  
Tissue Injury ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Expression Levels ◽  
Chronic Inflammatory Pain ◽  
Cytokines And Chemokines ◽  
Transient Receptor

Chronic inflammatory pain may result from peripheral tissue injury or inflammation, increasing the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines and chemokines. Transient receptor potential vanilloid 1 (TRPV1) is known to be involved in acute to subacute neuropathic and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are not elucidated. Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia were also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 3 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP, S100B, and RAGE were also involved. The expression levels of these molecules were reduced in EA and TRPV1−/− mice but not in the sham EA group. Our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

scholarly journals Intravenous administration of triptonide attenuates CFA-induced pain hypersensitivity through inhibiting AKT signaling pathway in mice

2020 ◽  
Author(s):  
Yue-Juan Ling ◽  
Ting-Yu Ding ◽  
Yong-Jing Gao ◽  
Bao-Chun Jiang
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Pain ◽  
Mechanical Allodynia ◽  
Interleukin 1 ◽  
Thermal Hyperalgesia ◽  
Paw Edema ◽  
Akt Inhibitor ◽  
Pain Hypersensitivity ◽  
Chronic Inflammatory Pain ◽  
Pro Inflammatory Cytokines

Abstract Background: Triptonide (TPN) is a major component of Tripterygium wilfordii Hook.f., and reportedly has anti-inflammatory and neuroprotective effects. Recent studies have demonstrated that the phosphatidylinositol 3-kinase (PI3K)/AKT pathway plays an important role in the pathogenesis of inflammatory pain. Here we investigated the anti-nociceptive effect of systemic treatment with TPN on mouse models of chronic inflammatory pain and explored possible mechanisms. Results: Unilateral hind paw injection of complete Freund’s adjuvant (CFA) induced paw edema and persistent pain hypersensitivity. Intravenous treatment with TPN attenuated CFA-induced paw edema, mechanical allodynia, and thermal hyperalgesia. Western blotting and immunofluorescence results showed that CFA induced AKT activation in the dorsal root ganglion (DRG) neurons, which was inhibited by TPN treatment. Furthermore, TPN treatment inhibited mRNA increase of proinflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), and Interleukin 6 (IL-6)] induced by CFA. Finally, pretreatment with AKT inhibitor, AKT inhibitor Ⅳ, attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, and decreased the mRNA expression of pro-inflammatory cytokines. Conclusions: These data indicate that TPN attenuates CFA-induced pain potentially via inhibiting AKT-mediated pro-inflammatory cytokines production in DRG. TPN may be used for the treatment of chronic inflammatory pain.

scholarly journals Neuregulin1-ErbB4 Signaling in Spinal Cord Participates in Electroacupuncture Analgesia in Inflammatory Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Chaofan Wan ◽  
Yunlong Xu ◽  
Baoyan Cen ◽  
Yucen Xia ◽  
Lin Yao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Inflammatory Pain ◽  
Life Quality ◽  
Thermal Hyperalgesia ◽  
Conditional Knockout ◽  
Inflammatory Factors ◽  
Complementary And Alternative Therapy ◽  
Genetic Ablation ◽  
Chronic Inflammatory Pain

Chronic inflammatory pain is a severe clinical symptom that aggravates the life quality of patients and places a huge economic burden on individuals and society. As one complementary and alternative therapy, electroacupuncture (EA) is widely used in clinical practice to treat chronic inflammatory pain based on its safety and efficacy. Previous studies have revealed the potential role of adenosine, neuropeptides, and inflammatory factors in EA analgesia in various pain models, but the identity of some of the signaling pathways involved remain unknown. In the present study, we explored whether neuregulin1 (NRG1)-ErbB4 signaling is involved in EA analgesia in inflammatory pain. Repeated EA treatment at the acupoints Zusanli (ST36) and Sanyinjiao (SP6) for 3 consecutive days remarkably attenuated mechanical allodynia and thermal hyperalgesia in complete Freund’s adjuvant (CFA)-treated mice, with an increased expression of NRG1 in spinal cord (SC). We found that ErbB4 kinase participated in both the EA and NRG1 mediated analgesic effects on inflammatory pain by pharmacological inhibition or genetic ablation ErbB4 in vivo. Intriguingly, the mice with conditional knockout of ErbB4 from PV+ interneurons in SC showed abnormal basal mechanical threshold. Meanwhile, NRG1 treatment could not relieve tactile allodynia in PV-Erbb4–/– mice or AAV-PV-Erbb4–/– mice after CFA injection. These experimental results suggest that regulating NRG1-ErbB4 signaling in SC could reduce pain hypersensitivity and contribute to EA analgesia in inflammatory pain.

scholarly journals Effects of Gastrodin on Analgesia and Inhibition of Ferroptosis

2021 ◽  
Author(s):  
JinYue Wang ◽  
Zhixian He ◽  
Xin Liu ◽  
Xing Wang
Keyword(s):  
Inflammatory Pain ◽  
Neurological Diseases ◽  
Central Area ◽  
Thermal Hyperalgesia ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Gas Treatment ◽  
Chronic Inflammatory Pain ◽  
Beneficial Effects ◽  
Thermal Pain

Abstract Background: Gastrodin possesses low toxicity and a broad range of pharmacological activities and exhibits beneficial effects in neurological diseases. This study investigated the effects of gastrodin (GAS) on analgesic, anti-inflammatory, anxiolytic and inhibition of ferroptosis. Materials and Methods: The chronic inflammatory pain model of C57BL/6J mice was established by hindpaw injection of complete Freund’s adjuvant (CFA). After GAS treatment, Thermal hyperalgesia test, Mechanical allodynia test, Elevated plus-maze (EPMT) and Open-field test (OFT) were performed to assess the behavioral changes of pain and anxiety. mRNAs of FTHI, GPX4, HO-1 and PTGS2 were measured by RT-qPCR. Results: In CFA-injected C57BL/6 mice, we found that the mechanical and thermal pain threshold was increased with treatment of GAS. In EPMT, the number of entries in open arms and retention times of open arms were increased by GAS. In the OFT, the time spent in the central area was also increased. Furthermore, GAS enhanced mRNA expressions of FTHI, GPX4 and H0-1, as well as decreased the expression of PTGS2 in a dose-dependent manner. Conclusion: GAS is effective in the treatment of mice chronic inflammatory pain and anxiety-like behaviors. It maybe exhibit potential neuroprotective effects through inhibition of ferroptosis.

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