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Objective:To observe any effect of electroacupuncture (EA) on the expression of phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) and phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) in the spinal dorsal horns of diabetics experiencing neuropathic pain.Methods:Eight rats were randomly selected from 30 healthy male Sprague-Dawley rats as the normal group (N), and the remaining twenty-two rats were treated with a single high-dose intraperitoneal injection of streptozotocin (STZ) to establish a neuropathic pain model. The rats modeled successfully were randomly divided into a model group (M, n=8) and an EA group ( n=8). In the EA group, electroacupuncture was applied at the bilateral Hou san li and Kunlun acupoints starting on the 15th day after the STZ injection. The daily sessions lasted 30 minutes for 1 week. Body weight (BW), fasting blood glucose (FBG) and paw withdrawal latency (PWL) were observed before the STZ injection and on the 7th, 14th, and 21st days afterward. The expression of p-ERK1/2 and p-CREB in the dorsal horns of the rats′ spinal cords was detected using western blotting. The count of p-CREB-positive cells in the dorsal horns and their co-localization with neurons was detected using immunofluorescence. Results:In comparison with the N group, the average BW of the M group on the 7th, 14th and 21st days after the STZ injection was significantly lower, while the average FBG was significantly higher. There was no significant difference between the M and N groups in the average PWL on the 7th day after the STZ injection, but it had decreased significantly in the M group on the 14th and 21st days. Compared with the M group, the average PWL of the EA group was significantly longer on the 21st day after the injection. The expression of p-ERK1/2 and p-CREB protein in the spines of the M group was significantly higher than in the N group. p-CREB positive cells were more numerous in the M group compared with the N group, while in the EA group they were fewer. P-CREB was co-located with neurons in the spinal dorsal horn.Conclusion:EA can alleviate neuropathic pain effectively, perhaps by inhibiting the expression of p-ERK1/2 and p-CREB in the dorsal horns of the spinal cord.
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Objective:To investigate the feasibility and safety of submaximal balloon dilation and to perform small-diameter stent for symptomatic carotid artery severely stenosis before coronary artery bypass grafting(CABG).Methods:From January 2016 to December 2019, 30 patients of the Department of Neurointervention in Beijing Anzhen Hospital with symptomatic carotid artery stenosis(≥70%) and the left main trunk or triple-vessel of coronary artery disease were analyzed retrospectively. General information, clinical characteristics, and imaging data of all cases were collected. All patients underwent submaximal balloon dilation and small-diameter stent implantation. Preoperative comorbidities or risk factors included hypertension 23 cases(76.7%), diabetes 10 cases(33.3%), hyperglycemia 14 cases(46.7%), moking 13 cases(43.3%). Left main trunk disease 6 cases(20.0%), three-vessels disease 24 cases(80.0%), mitral regurgitation 1 case(3.3%), stable angina 25 cases(83.3%), myocardial infarction 8 cases(26.7%), cerebral infarction 24 cases(80.0%) and transient ischemia attack(TIA) 6 cases(20.0%) caused by ipsilateral carotid artery stenosis. The median National Institutes of Health Stroke Scale(NIHSS) score was 2(0-3), and the median modified Rankin Scale(mRS) score was 1(0-1) before the operation. The mean interval between carotid artery intervention and CABG was(23.4±8.2)days.Results:29 cases(96.7%, 29/30) underwent CAS-CABG operation successfully. In one case of carotid artery extreme tortuosity, the emboli protective device could not place the distal carotid artery. In the operative procedure, 27 cases(90.0%, 27/30) underwent with 3mm diameter balloon, only 3 cases(10.0%) with 3 mm balloon after pre-dilatation with 2 mm diameter balloon because of severely high-grade stenosis(99%). 25 cases(83.3%) with 7mm diameter stents and 5 cases(16.7%) with 6 mm diameter stents, including 22 cases(73.3%) with a closed-cell stent and 8 cases(26.7%) with an open-cell stent. In the perioperative period, the heart rate of two patients was lower than 50 BPM during operation and returned to normal after using atropine immediately. Another patient presented with chest tightness during interventional therapy. TNI elevation was examined urgently. After oxygen inhalation and intravenous infusion of Nitroglycerin, the patient's symptoms improved rapidly. No cardiac and cerebrovascular complications occurred during the perioperative period of CABG, no cardiac-related complications occurred within 30 days of follow-up, one case of TIA and 1 case of cerebral infarction. After intensive anti-platelet aggregation and lipid-lowering treatment, two patient's symptoms improved. There were no death cases in all patients during carotid artery interventional therapy, perioperative CABG and 30-day follow-up. Thirty days later, we performed a clinical follow-up of 23 cases, median 4.5(3.0-7.9) months, mRS Score Median 1(0-1). One patient presented with TIA, any patient had no symptoms of the cardiac or nervous system. Image follow-up of 17 cases, median 3.5(2.8-4.5) months, carotid artery ultrasound showed in-stent restenosis(stenosis rate>50%) in 1 case, the patient was asymptomatic restenosis, continue treatment of aggressive anti-platelet and lipid-lowering drugs.Conclusion:Submaximal balloon dilation and performing small-diameter stent for symptomatic carotid artery severely stenosis before CABG is safe and feasible, which could not only reduce the incidence of vagus reflex resulted in acute coronary syndrome during carotid artery stenosis intervention but also morbidity of acute ischemic stroke events during CABG.
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Objective To investigate the effects of low frequency electroacupuncture on the P2X3 receptor expres-sion in dorsal root ganglion ( DRG) of rats with type II diabetic neuropathic pain. Methods Part 1:Fifty normal SD rats were randomly divided into normal group (8 rats) and model group (42 rats). The rat model of type II diabetic neuropathic pain was generated by high fat and high sugar diet with a single intraperitoneal injection of streptozotocin ( STZ, 35 mg/kg) . 2 Hz electroacupuncture was administered at ipsilateral acupoints Zusanli and Kunlun for consecutive 7 days. Insulin sensitivity index ( ISI) was measured at 0 w and 5 w, and fasting plasma glucose ( FPG) was measured at 0 w, 5 w, and 7 w. Paw withdrawal threshold (PWT) was measured by mechanical pain threshold, and P2X3 receptor was determined by immunofluorescence. Part 2:Twelve rats with diabetic neuropathic pain (DNP) were divided into EA + vehicle group (6 rats) and EA + αβ?meATP group (6 rats). Rats in the two groups received the same EA treatment as Part 1. Rats in the EA + αβ?meATP group were injected with P2X3 receptor agonistαβ?meATP (0. 6μmol/L, 100μL) into the ventral sur?face of each hind paw every time before EA treatment. Rats in the EA + vehicle group received the same dose of vehicle ( PBS buffer) as a control. Pain threshold of the rats were measured. Results ① Compared with the normal group, the ISI levels of the rats in DNP group was significantly decreased after 5 weeks of the high?fat high?sugar diet (P < 0. 01). Two weeks after STZ injection, the fasting plasma glucose levels in the rats receiving STZ were significantly elevated ( P <0. 01 ) . The type 2 diabetes model was established with a successful rate of 69. 04%. ②PWTs:The PWTs of rats in DNP group were reduced compared with rats in the normal group (P < 0. 01), indicating that the type 2 DNP model was suc?cessfully established. Compared with the PWTs of DNP?controlled rats, the 2 Hz electroacupuncture significantly increased bilateral PWT of rats subjected to DNP from day 3 after treatment (P < 0. 01). P2X3 receptor agonistαβ?meATP greatly reduced bilateral PWT of EA?treated DNP rats compared with that of the EA + vehicle group (P < 0. 01). ③The immu?nofluorescence essay showed that P2X3 receptor expression in bilateral L5 DRGs in the DNP group was significantly in?creased as compared with that in the normal group ( P < 0. 01 ) . The increases were inhibited by 2 Hz EA in L5 DRGs compared with the DNP group (P < 0. 01). Conclusions 2Hz electroacupuncture can effectively treat the type II diabet?ic neuropathic pain by decreasing the expression of L5 DRG P2X3 receptors in rats.
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Objective To explore the effect of low-frequency electroacupuncture (EA) on neuropathic pain induced by spinal nerve injury and its underlying mechanism.Methods Thirty-two male Sprague-Dawley rats were randomly divided into a normal group,a sham spared nerve injury (SNI) group,an SNI group and an SNI+EA group,each of 8.The rats in the SNI and SNI+EA groups were given SNI surgery,while those of the sham-SNI group only had the sciatic nerve and its branches exposed without any lesion.EA at 2 Hz was applied over the ipsilateral Zusanli and Kunlun acupoints daily for 14 days after the surgery.The ipsilateral paw withdrawal threshold (PWT) was measured,along with protein kinase A (PKA) levels in the dorsal horn of the spinal cord,calcitonin gene-related peptide (CGRP) and substance P (SP) levels along with transient receptor potential V1 (TRPV1).Results Compared to the normal group,the SNI groups all showed significant decreases in their PWTs on the affected side and significant increases in PKA,TRPV1,CGRP and substance P on the affected side.Compared to SNI group,the average ipsilateral PWT in the SNI+EA group increased significantly after EA treatment,while PKA levels,TRPV1,CGRP levels and SP expression all decreased significantly.Conclusion Electroacupuncture at low frequency can effectively relieve neuropathic pain,perhaps through down-regulation of PKA in the spinal cord and by decreasing pain hypersensitivity related to CGRP and SP.
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Long terms of chronic pain may induce emotional disorder such as depression,anxiety and aversion.It is worthy of studying the mechanism and therapy on pain emotional disorder.The animal model is important in basic researches,and the quantitative evaluation methods on the psychiatric factors are gradually applied in the pain research.The methods of evaluating the psychiatric disorder of pain are discussed in this paper,which will provide theory basis in the relevant fields.
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Objective To investigate the change of mu opioid receptor ( MOR) in dorsal root ganglion ( DRG) in rat chronic inflammatory pain model and the effect of MOR agonist and antagonis tintraplantarly ( i.pl.) injected on pain threshold, so as to determine the role of peripheral MOR in chron in inflammatory pain .Methods Chronicin flammatory pain model was established by i .pl.injection of CFA in rats.The expression of MOR in DRG was detected by immunohistochemistry .Pain threshold before and after i .pl.injection of MOR agonist and antagonist was measured by radiant heat method .Results Rats suffered from an intraplantar injection of CFA developed chronic inflammatory pain , and the painthreshold still reduced on 18 day after CFA injection compared to that in the normal group . Immunohistochemistry staining revealed that compared with the normal group , the expression of MOR in DRG of CFA rats was increased ( P<0.01 ) .After the paw dorsal surface injection of MOR agonist , the pain threshold of CFA rats was increased, while that of normal rats exhibited no significant change .After the paw dorsal surface injection of MOR antagonist, the pain threshold of CFA rats was reduced , while that of normal rats had no significant change .Conclusion Under chronic inflammatory pain condition , DRG MOR expressionis enhanced , which participates in the regulation of chronic inflammatory pain , and may contribute to the prevention of further more serious pain .
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Diabetic neuropathic pain(DNP)is one of the most common complications in clinical, which influenced patients’ daily functions greatly, without clear mechanisms and effective methods.P2X3 receptors play a pivotal role in the formation, transmission and conduction of pain under neuropathic pain models, associated with peripheral sensory nerve excitability enhancement.This paper focuses on the establishment of DNP models, and the effects of P2X3 receptors in diabetes mellitus.
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<p><b>OBJECTIVE</b>To observe the analgesic effect of electroacupuncture (EA) on collagen-induced arthritis (CIA) rats and its regulating effect on inflammation reaction and the endogenous opioid system of synovial tissues. Methods A total of 30 healthy male Wistar rats were randomly divided into a control group, a model group and an EA group, 10 rats in each one. The chronic pain model of CIA rats was made by cattle type-II collagen in the model group and EA group. Rats in the EA group were treated with EA at "Zusanli" (ST 36) and "Kunlun" (BL 60) for 30 min from 16th day after model establishment, once a day for consecutive 10 days. Rats in the control group did not receive any treatment. Rats in the model group were treated with fixation as the EA group. Threshold of pain, arthritis index, paw swelling were measured before model establishment and 16 d, 20 d, 23 d and 25 d after model establishment. The levels of beta-endorphin (β-END), met-enkephalin (met-ENK), dynorphin A (Dyn A) were measured by radioimmunoassay; the mRNA expressions of mu opioid receptor (MOR), kappa opioid receptor (KOR) and delta opioid receptor (DOR) in synovial tissues of CIA rats were detected by I quantitative polymerase chain reaction (qPCR).</p><p><b>RESULTS</b>Compared with the control group, threshold of pain was reduced (all P<0. 01), arthritis index was increased (all P<0. 01) and paw swelling was increased (all P<0. 01) in the model group on the 16th day, 20th day, 23rd day, 25th day after model establishment. Compared with the model group, the threshold of pain was increased in the EA group (all P<0. 01), arthritis index and paw swelling were reduced (all P<0. 01) on the 23rd day and 25th day after model establishment. Compared with the control group, the level of Dyn A in synovial tissues of CIA rats was increased in the model group (P<0. 01); the mRNA expressions of MOR, KOR and DOR were down-regulated lower than 0. 5 fold of normal level. Compared with the model group, the level of β-END in synovial tissues of the knee joint was increased in the EA group (P<0. 05), and the mRNA expressions of MOR, KOR and DOR in synovial tissues of CIA rats were up-regulated more than 2 folds of normal level.</p><p><b>CONCLUSION</b>The intervention of EA on chronic pain of CIA rats is superior, which is likely to be related with effects of EA on anti-inflammation and up-regulation of synovial tissue β-END and MOR, KOR, DOR.</p>
Subject(s)
Animals , Cattle , Humans , Male , Rats , Acupuncture Analgesia , Acupuncture Points , Analgesics, Opioid , Allergy and Immunology , Arthritis, Rheumatoid , Allergy and Immunology , Therapeutics , Chronic Pain , Allergy and Immunology , Therapeutics , Dynorphins , Genetics , Allergy and Immunology , Electroacupuncture , Enkephalin, Methionine , Genetics , Allergy and Immunology , Rats, Wistar , Receptors, Opioid, mu , Genetics , Allergy and Immunology , Synovial Fluid , Allergy and Immunology , beta-Endorphin , Genetics , Allergy and ImmunologyABSTRACT
@#Objective To investigate the effect of electroacupuncture with low frequency on pain sensitization of neuropathic pain rats,and the possible mechanism of regulating peripheral pain sensitization. Methods Rat neuropathic pain model was established with the right L5 spinal nerve ligation. Zusanli (ST36) and Kunlun (BL60) were selected for electroacupuncture intervention. Mechanical allodynia, and the levels of stransient receptor potential vanilloid type 1 (TRPV1) and substance P (SP) in ipsilateral L5 and L4 dorsal root ganglion (DRG) were tested. A further validation experiment with TRPV1 agonist 6'-IRTX was carried out. Results Rats suffered from L5 spinal nerve ligation showed obvious pain sensitization. The levels of TRPV1 in ipsilateral L4 DRG and SP in ipsilateral L5 DRG were significantly elevated.Electroacupuncture with low frequency significantly relieved pain sensitization, and suppressed TRPV1 and SP increase. 6'-IRTX intraperitoneally administered significantly counteracted the anti-pain sensitization action of electroacupuncture with low frequency. Conclusion Electroacupuncture with low frequency is effective on neuropathic pain by intervening pain sensitization, which may be related to the regulation of DRG TRPV1 and SP.