scholarly journals Effect of Electroacupuncture on Hyperalgesia and Vasoactive Neurotransmitters in a Rat Model of Conscious Recurrent Migraine

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Xiaobai Xu ◽  
Lu Liu ◽  
Luopeng Zhao ◽  
Bin Li ◽  
Xianghong Jing ◽  
...  
Keyword(s):  
Rat Model ◽  
Single Point ◽  
Plasma Concentrations ◽  
Thermal Hyperalgesia ◽  
Acupuncture Point ◽  
Acupuncture Points ◽  
Tail Flick ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase ◽  
Perivascular Nerves

Migraine onset is associated with the abnormal release of vasoactive neurotransmitters from perivascular nerves, and these neurotransmitters are involved in the pathophysiology of migraine. Hyperalgesia is a key feature of migraine, and accumulating evidence indicates that electroacupuncture (EA) at the single acupuncture point (Fengchi [GB20]) is effective in ameliorating hyperalgesia. In clinical practice, multiple acupuncture points are widely used, especially GB20 and Yanglingquan (GB34). However, the role played by vasoactive neurotransmitters in acupuncture antihyperalgesic effect at the single or multiple acupuncture points remains unknown. We aimed to determine whether EA would exert its antihyperalgesic effects by modulating vasoactive neurotransmitter release from the perivascular nerves. Furthermore, we examined whether targeting multiple acupuncture points would be more effective than targeting a single point in reducing hyperalgesia. The mechanical and thermal hyperalgesia were evaluated by measuring the facial and hind-paw mechanical withdrawal thresholds, tail-flick and hot-plate latencies. Plasma concentrations of vasoactive neurotransmitters were determined using rat-specific ELISA kits from jugular vein, including calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), pituitary adenylate cyclase-activating polypeptide (PACAP), nitric oxide (NO), and endothelin-1 (ET-1). The result suggested that EA significantly ameliorated the mechanical and thermal hyperalgesia, reduced c-Fos levels in the trigeminal ganglion, and attenuated plasma and dural levels of vasoactive neurotransmitters, especially in the multiple acupuncture points group (GB20+GB34). In conclusion, EA exerts antihyperalgesic effect in a rat model of conscious recurrent migraine, possibly via modulation of the vasoactive neurotransmitters. Furthermore, targeting multiple acupuncture points is more effective than targeting a single point in reducing hyperalgesia.

scholarly journals Neuropeptide changes in an improved migraine model with repeat stimulations

2021 ◽  
Vol 12 (1) ◽  
pp. 523-532
Author(s):  
Yichen Guo ◽  
Yawen Cheng ◽  
Jiaqi An ◽  
Yi Qi ◽  
Guogang Luo
Keyword(s):  
Rat Model ◽  
Medical Condition ◽  
Future Research ◽  
Trigeminal Ganglia ◽  
Trigeminovascular System ◽  
Dynamic Changes ◽  
Repeated Stimulation ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase ◽  
Stimulation Of

Abstract Migraine is a medical condition with a severe recursive headache. The activation of the trigeminovascular system is an important mechanism. The neuropeptide calcitonin gene-related peptide (CGRP) plays a crucial role in the pathogenesis of migraine. Several other neuropeptides are also involved; however, their roles in migraine remain unclear. In this study, using a rat model of migraine induced by electrical stimulation of the trigeminal ganglia (TG) and an improved version induced with repeated stimulation, we observed the dynamic changes of these peptides in TG and blood. We demonstrated that the expression of CGRP, pituitary adenylate cyclase activating polypeptide (PACAP), neuropeptide Y (NPY), vasoactive intestinal peptide, and nociceptin in TG was significantly elevated and peaked at different time points after a single stimulation. Their levels in the blood plasma were significantly increased at 12 h after stimulation. The peptides were further elevated with repeated stimulation. The improved rat model of migraine with repeated stimulation of TG resulted in a more pronounced elevation of CGRP, PACAP, and NPY. Thus, the dynamic changes in neuropeptides after stimulation suggest that these neuropeptides may play an important role in the pathogenesis of migraine. Additionally, the migraine model with repetitive stimulation would be a novel model for future research.

Electroacupuncture Relieves Labour Pain and Influences the Spinal Dynorphin/κ-Opioid Receptor System in Rats

2016 ◽  
Vol 34 (3) ◽  
pp. 223-228 ◽  
Author(s):  
Qiu-Yan Jiang ◽  
Meng-Ying Wang ◽  
Li Li ◽  
Hai-Xia Mo ◽  
Jin-Ling Song ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Opioid Receptor ◽  
Rat Model ◽  
Acupuncture Point ◽  
Labour Pain ◽  
Mechanisms Of Action ◽  
Lumbar Spinal Cord ◽  
Control Group ◽  
Tail Flick ◽  
Underlying Mechanisms

Background The dynorphin (DYN)/κ-opioid receptor (KOR) system plays a key role in the control of labour pain. Our previous clinical study reported that electroacupuncture (EA) provided intrapartum analgesia, but the underlying mechanisms of action have not been fully elucidated. Aims To observe the effect of EA on labour pain and to explore the underlying mechanisms of action in a rat model. Methods Copulation-confirmed pregnant rats (n=120) were given castor oil to induce labour. Rats remained untreated (control group, n=20) or received either meperidine (an opioid that is commonly used to treat labour pain, n=20) or EA at SP6, LI4, SP6+LI4 or SP10 (four groups, n=20 each). Labour pain was evaluated by the warm water tail-flick test. Serum DYN values were measured by ELISA. Protein and mRNA expression of prodynorphin (PDYN, the precursor protein of DYN) and KOR were analysed by Western blotting and real-time PCR, respectively. Results EA treatment at all acupuncture point combinations studied significantly relieved labour pain and increased serum DYN concentrations, to a degree similar to that achieved with meperidine. EA notably enhanced protein expression of KOR and PDYN and mRNA expression in the lumbar spinal cord but not in the cerebral cortex. The size of effect varied by EA group in the order: SP6>LI4>SP6+LI4>SP10 for all parameters measured, indicating differential effects relating to acupuncture point selection/combination. Conclusions The present study indicates that EA relieves labour pain, at least in part, by regulation of the spinal DYN/KOR system in a rat model.

scholarly journals Buprenorphine Metabolites, Buprenorphine-3-glucuronide and Norbuprenorphine-3-glucuronide, Are Biologically Active

2011 ◽  
Vol 115 (6) ◽  
pp. 1251-1260 ◽  
Author(s):  
Sarah M. Brown ◽  
Michael Holtzman ◽  
Thomas Kim ◽  
Evan D. Kharasch
Keyword(s):  
Radioligand Binding ◽  
Competitive Inhibition ◽  
Antinociceptive Effect ◽  
Plasma Concentrations ◽  
Parent Drug ◽  
Biologically Active ◽  
Whole Body ◽  
Tail Flick ◽  
High Affinity

Background The long-lasting high-affinity opioid buprenorphine has complex pharmacology, including ceiling effects with respect to analgesia and respiratory depression. Plasma concentrations of the major buprenorphine metabolites norbuprenorphine, buprenorphine-3-glucuronide, and norbuprenorphine-3-glucuronide approximate or exceed those of the parent drug. Buprenorphine glucuronide metabolites pharmacology is undefined. This investigation determined binding and pharmacologic activity of the two glucuronide metabolites, and in comparison with buprenorphine and norbuprenorphine. Methods Competitive inhibition of radioligand binding to human μ, κ, and δ opioid and nociceptin receptors was used to determine glucuronide binding affinities for these receptors. Common opiate effects were assessed in vivo in SwissWebster mice. Antinociception was assessed using a tail-flick assay, respiratory effects were measured using unrestrained whole-body plethysmography, and sedation was assessed by inhibition of locomotion measured by open-field testing. Results Buprenorphine-3-glucuronide had high affinity for human μ (Ki [inhibition constant] = 4.9 ± 2.7 pM), δ (Ki = 270 ± 0.4 nM), and nociceptin (Ki = 36 ± 0.3 μM) but not κ receptors. Norbuprenorphine-3-glucuronide had affinity for human κ (Ki = 300 ± 0.5 nM) and nociceptin (Ki = 18 ± 0.2 μM) but not μ or δ receptors. At the dose tested, buprenorphine-3-glucuronide had a small antinociceptive effect. Neither glucuronide had significant effects on respiratory rate, but norbuprenorphine-3-glucuronide decreased tidal volume. Norbuprenorphine-3-glucuronide also caused sedation. Conclusions Both glucuronide metabolites of buprenorphine are biologically active at doses relevant to metabolite exposures, which occur after buprenorphine. Activity of the glucuronides may contribute to the overall pharmacology of buprenorphine.

Is There a Difference between the Effects of One-Point and Three-Point Indirect Moxibustion Stimulation on Skin Temperature Changes of the Posterior Trunk Surface?

2012 ◽  
Vol 30 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Hidetoshi Mori ◽  
Tim Hideaki Tanaka ◽  
Hiroshi Kuge ◽  
Ken Sasaki
Keyword(s):  
Skin Temperature ◽  
Single Point ◽  
Indirect Moxibustion ◽  
Thermal Stimulation ◽  
Acupuncture Points ◽  
Lumbar Region ◽  
Temperature Changes ◽  
Posterior Trunk ◽  
The One ◽  
Stimulation Group

Objective To determine whether any difference exists in responses to indirect moxibustion relative to thermal stimulation sites. Methods Twenty one healthy men of mean±SD age 22.5±6.1 years were randomly divided into two groups, one receiving a single moxibustion stimulation in three locations (the three-point stimulation group, n=10 participants) and the other receiving three stimulations in one location (the one-point stimulation group, n=11 participants). The thermal stimulation sites were GV14, GV9 and GV4 acupuncture points. A thermograph was used to obtain the skin temperature on the posterior trunks of the participants. To analyse skin temperature, four arbitrary frames (the scapular, interscapular, lumbar and vertebral regions) were made on the posterior trunk. Result An increase in skin temperature on the posterior trunk was observed following both one- and three-point moxibustion administrations. The skin temperature of the lumbar region showed a significant increase after three-point stimulation compared with single-point stimulation (p=0.011). There was also a significant increase in skin temperature of the spinal region after three-point stimulation compared with one-point stimulation (p=0.046). Conclusion Administration of single moxibustion doses on the GV14, GV9 and GV4 points produces greater changes in skin temperature than three applications of moxibustion to the GV14 point only.

scholarly journals Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

2019 ◽  
Vol 65 (9) ◽  
pp. 1188-1192
Author(s):  
Erkan Kilinc ◽  
Handan Gunes
Keyword(s):  
Interleukin 1 ◽  
Plasma Concentrations ◽  
Onset Time ◽  
Epileptic Seizures ◽  
Clonic Seizure ◽  
Tonic Clonic Seizure ◽  
Interleukin 1 Beta ◽  
Calcitonin Gene ◽  
Epilepsy Treatment ◽  
Dual Action

SUMMARY OBJECTIVE We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1β) in pentylenetetrazol-induced seizures in rats. METHODS Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine’s scale, and plasma CGRP, SP, and IL-1β concentrations were measured using ELISA. RESULTS Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1β concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1β concentrations. However, obestatin did not change CGRP, SP, and IL-1β concentrations. CONCLUSION Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.

Effects of CGRP receptor antagonism in nitroglycerin-induced hyperalgesia

Cephalalgia ◽  
2013 ◽  
Vol 34 (8) ◽  
pp. 594-604 ◽  
Author(s):  
R Greco ◽  
AS Mangione ◽  
F Siani ◽  
F Blandini ◽  
M Vairetti ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Formalin Test ◽  
Tail Flick ◽  
Cgrp Receptor ◽  
Tail Flick Test ◽  
Nociceptive Transmission ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists ◽  
Cgrp Receptor Antagonist ◽  
Trigeminal Nerves

Background The release of calcitonin gene-related peptide (CGRP) from trigeminal nerves plays a central role in the pathophysiology of migraine and clinical evidence shows an antimigraine effect for CGRP receptor antagonists. Systemic administration of nitroglycerin (NTG), a nitrovasodilator, consistently provokes spontaneous-like migraine attacks in migraine sufferers; in the rat, systemic NTG induces a condition of hyperalgesia, probably through the activation of cerebral/spinal structures involved in nociceptive transmission. Aim The aim of this article is to test the analgesic effect of the CGRP receptor antagonist MK-8825 in two animal models of pain that may be relevant for migraine: the tail flick test and the formalin test performed during NTG-induced hyperalgesia. Results MK-8825 showed analgesic activity when administered alone at both the tail flick test and the formalin test. Furthermore, the CGRP antagonist proved effective in counteracting NTG-induced hyperalgesia in both tests. MK-8825 indeed reduced the nociceptive behavior when administered either simultaneously or prior to (30–60 minutes before) NTG. Conclusion These data suggest that MK-8825 may represent a potential therapeutic tool for the treatment of migraine.

scholarly journals Spinal interleukin-17 promotes thermal hyperalgesia and NMDA NR1 phosphorylation in an inflammatory pain rat model

Pain ◽  
2013 ◽  
Vol 154 (2) ◽  
pp. 294-305 ◽  
Author(s):  
Xianze Meng ◽  
Yu Zhang ◽  
Lixing Lao ◽  
Rikka Saito ◽  
Aihui Li ◽  
...  
Keyword(s):  
Rat Model ◽  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Interleukin 17

LncRNA PCAT19 Regulates Neuropathic Pain via Regulation of miR-182-5p/JMJD1A in a Rat Model of Chronic Constriction Injury

2021 ◽  
pp. 1-9
Author(s):  
Miao Huo ◽  
Xingxing Zheng ◽  
Ning Bai ◽  
Ruifen Xu ◽  
Guang Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Rat Model ◽  
Noncoding Rna ◽  
Thermal Hyperalgesia ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Inflammatory Factor ◽  
Reporter Assay ◽  
Withdrawal Threshold ◽  
Dual Luciferase Reporter Assay

<b><i>Introduction:</i></b> Neuropathic pain (NP) is one of the most severe chronic pain types. In recent years, more and more studies have shown that long noncoding RNA (LncRNA) plays a key role in a variety of human diseases, including NP. However, the role of LncRNA prostate cancer-associated transcript 19 (PCAT19) in NP and its specific mechanism remain unclear. <b><i>Methods:</i></b> A chronic constrictive injury (CCI) rat model was established. Rat paw withdrawal threshold and paw withdrawal latency were used to evaluate the neuronal pain behavior of rats in this model. mRNA expression of PCAT19, neuroinflammatory factor, microRNA (miR)-182-5p, and Jumonji domain containing 1A (JMJD1A) were detected by quantitative real-time PCR. ELISA analysis was used to detect inflammatory factor protein expression. Dual-luciferase reporter assay was used to evaluate the targeting relationship between genes. <b><i>Results:</i></b> PCAT19 was continuously upregulated in CCI rats. miR-182-5p was the target of PCAT19, and miR-182-5p was increased after PCAT19 knockdown. NP behaviors such as mechanical ectopic pain and thermal hyperalgesia as well as neuroinflammation can be reduced by knocking down PCAT19. However, the injection of miR-182-5p antagomir significantly reversed the level of the NP behaviors and neuroinflammation caused by PCAT19 knockdown. Besides, dual-luciferase reporter assay showed that JMJD1A was the target gene of miR-182-5p. The level of JMJD1A in CCI rats increased with time. After PCAT19 knockdown, JMJD1A was significantly decreased, but inhibition of miR-182-5p can reverse its levels. <b><i>Conclusion:</i></b> This study shows that PCAT19 plays a role in NP by targeting the miR-182-5p/JMJD1A axis, and PCAT19 can be used as a new therapeutic target for NP.

scholarly journals Acetaminophen (Paracetamol) Metabolites Induce Vasodilation and Hypotension by Activating Kv7 Potassium Channels Directly and Indirectly

2020 ◽  
Vol 40 (5) ◽  
pp. 1207-1219 ◽  
Author(s):  
Jennifer van der Horst ◽  
Rian W. Manville ◽  
Katie Hayes ◽  
Morten B. Thomsen ◽  
Geoffrey W. Abbott ◽  
...  
Keyword(s):  
Preventive Intervention ◽  
Ex Vivo ◽  
Calcitonin Gene Related Peptide ◽  
Mesenteric Arteries ◽  
Benzoquinone Imine ◽  
Kv7 Channels ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Perivascular Nerves ◽  
Life Threatening

Objective: Intravenous acetaminophen/paracetamol (APAP) is well documented to cause hypotension. Since the patients receiving intravenous APAP are usually critically ill, any severe hemodynamic changes, as with those associated with APAP, can be life-threatening. The mechanism underlying this dangerous iatrogenic effect of APAP was unknown. Approach and Results: Here, we show that intravenous APAP caused transient hypotension in rats, which was attenuated by the Kv7 channel blocker, linopirdine. APAP metabolite N-acetyl-p-benzoquinone imine caused vasodilatation of rat mesenteric arteries ex vivo. This vasodilatation was sensitive to linopirdine and also the calcitonin gene-related peptide antagonist, BIBN 4096. Further investigation revealed N-acetyl-p-benzoquinone imine stimulates calcitonin gene-related peptide release from perivascular nerves, causing a cAMP-dependent activation of Kv7 channels. We also show that N-acetyl-p-benzoquinone imine enhances Kv7.4 and Kv7.5 channels overexpressed in oocytes, suggesting that it can activate Kv7.4 and Kv7.5 channels directly, to elicit vasodilatation. Conclusions: Direct and indirect activation of Kv7 channels by the APAP metabolite N-acetyl-p-benzoquinone imine decreases arterial tone, which can lead to a drop in blood pressure. Our findings provide a molecular mechanism and potential preventive intervention for the clinical phenomenon of intravenous APAP-dependent transient hypotension.

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