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Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice. Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE
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OBJECTIVE: To observe the effect of bone-edge electroacupuncture (EA) intervention on mechanical pain threshold (PT) and expression of G protein-coupled receptor kinase (GRK5), β-arrestin 2, total and phosphorylated PKC alpha (p-PKCα) proteins in the locus coeruleus (LC) of rats with bone cancer pain induced morphine tolerance, so as to reveal its partial central mechanisms underlying pain relief. METHODS: Forty SD rats were randomly divided into 5 groups, namely sham bone cancer, bone cancer pain, morphine tolerance, bone-edge EA, and sham EA (n＝ 8 rats in each group). The bone cancer with morphine tolerance model was established by intramedullary injection of MRMT-1 cells into the tibial cavity, and then intraperitoneal injection of morphine hydrochloride injection. After successful establishment of morphine tolerance model, the bone-edge EA (2 Hz/100 Hz，0.5－1.5 mA) was applied to bilateral "Zusanli" (ST36) and "Kunlun" (BL60) for 30 min, once a day for 7 days, after inserting the needle-tip to the tibial bone surface. The ipsilateral mechanical paw withdrawal thresholds (PWTs) were detected dynamically. The expression levels of GRK5, β-arrestin 2, PKCα and p-PKCα in the LC area were measured by Western blot. RESULTS: The PWTs of bone cancer pain rats were decreased on day 10 after inoculation of cancer cells (P0.05). The PWTs were significantly increased in the bone-edge EA intervention group (P0.05). In comparison with the sham bone cancer group, the expression of GRK5 protein in morphine tolerance group was significantly decreased (P<0.01); compared with morphine tolerance group, the expression of GRK5 protein in bone-edge EA group was increased(P<0.01). In comparison with the sham bone cancer group, the expression of β-arrestin 2 and p-PKCα in bone cancer group significantly increased (P<0.01). After the intervention, the increased β-arrestin 2 and p-PKCα expressions were reversed in the bone-edge EA group (P<0.01); compared with morphine tolerance group and sham EA group, the expression of PKCα protein was decreased(P<0.01). CONCLUSION: Bone-edge EA can effectively relieve morphine tolerance in bone cancer pain rats, which may be related to its functions in up-regulating GRK5 protein and down-regulating β-arrestin 2, PKCα and p-PKCα proteins in LC. .
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OBJECTIVE@#To observe the expression of GABA receptor mRNA in different brain regions of the central nervous system in chronic inflammatory pain rats and the intervention effect of electroacupuncture (EA).@*METHODS@#A total of 48 SPF male SD rats were randomly divided into a blank control group, a model control group, an EA group and a sham EA group, 12 rats in each group. The model of chronic inflammatory pain was established by injecting Freund's complete adjuvant into the foot. The EA group was treated with EA 28 days after the model establishment. The "Housanli" (ST 36) and "Kunlun" (BL 60) were selected and treated with dilatational wave, 2 Hz/100 Hz in frequency, 0.5-1.5 mA for 30 min; EA was given only once. In the sham EA group, the same acupoints were selected but the needles were only inserted into subcutaneous area; EA was connected for 30 min without electrical stimulation. The behavior changes of mechanical pain threshold and thermal pain threshold before model establishment, 1 day, 3 days, 7 days, 14 days, 21 days and 28 days after the model establishment as well as emotional behavior 29 days after the model establishment were observed; the relative expressions of GABA receptor mRNA in anterior cingulate cortex, amygdala and hypothalamus were observed.@*RESULTS@#Compared with the blank control group, the change rates of mechanical pain threshold and thermal pain threshold in the model control group were decreased significantly 1 day, 3 days, 7 days, 14 days, 21 days, 28 days after model establishment (0.05). Compared with the blank control group, the expression of GABA receptor mRNA in the amygdala was decreased significantly in the model control group (<0.01); compared with the model control group and the sham EA group, the expression of GABA receptor mRNA in amygdala was increased after intervention in the EA group (<0.01).@*CONCLUSION@#Single treatment of EA could significantly increase the mechanical pain threshold and thermal pain threshold, improve abnormal emotional behavior in rats with chronic inflammatory pain, which may be related to the increasing of expression of GABA receptor mRNA in the amygdala.
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OBJECTIVE@#To observe the effect of early intervention of bone-nearby acupuncture (BNA) combined with electroacupuncture (EA) on the expression of histone deacetylase1(HDAC1), histone deacetylase 2 (HDAC2) andμ-opioid recepter (MOR) in dorsal root ganglia (DRG) of bone cancer pain-morphine tolerance (BCP-MT) rats, and to explore its possible mechanism.@*METHODS@#A total of 35 SD rats were randomized into a sham BCP group (=6), a BCP group (=7), a MT group (=7), a BNA+EA group (=8) and a shame BNA group (=7). Except of the sham BCP group, cancer cell inoculation operation at left tibia was given in the other 4 groups to establish the bone cancer pain model. In the MT group, the BNA+EA group and the shame BNA group, intraperitoneal injection of morphine hydrochloride was given to establish the morphine tolerance model. After the operation, bone-nearby acupuncture combined with electroacupuncture was applied at "Zusanli" (ST 36) and "Kunlun" (BL 60) in the BNA+EA group, with dilatational wave, 2 Hz/100 Hz in frequency, 0.5 to 1.5 mA in intensity. Intervention in the shame BNA group was applied at the same time and acupoints as those in the BNA+EA group, the needles were pierced the skin without any electrical stimulation. The needles were retained for 30 min, once a day for continuous 7 days in both BNA+EA and shame BNA groups. Before and 10, 11, 15, 22 days after the operation, the left paw withdrawal threshold (PWT) was measured in the 5 groups. The levels of HDAC1, HDAC2 and MOR in DRG were detected by Western blot.@*RESULTS@#Ten days after the cancer cell inoculation operation, the PWT of the BCP, MT, BNA+EA and sham BNA groups was decreased compared with the sham BCP group (0.05); the PWT of the BNA+EA group was increased compared with the MT and sham BNA group (<0.01). In the BCP group, the DRG levels of HDAC1 and HDCA2 were increased, while the level of MOR was decreased compared with the sham BCP group (<0.05, <0.01). In the MT group, the DRG level of HDAC1 was increased compared with the BCP group (<0.05). In the BNA+EA group, the DRG level of HDAC1 was decreased compared with the MT group and the sham BNA group (<0.01, <0.05), while the level of MOR was increased (<0.01).@*CONCLUSION@#Early intervention of bone-nearby acupuncture combined with electroacupuncture can relieve the morphine tolerance in bone cancer pain rats, it may relate to down-regulating the expression of HDAC1 and up-regulating the expression of MOR in the dorsal root ganglia.
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Animais , Ratos , Pontos de Acupuntura , Neoplasias Ósseas , Dor do Câncer , Terapêutica , Tolerância a Medicamentos , Eletroacupuntura , Gânglios Espinais , Metabolismo , Histona Desacetilases , Metabolismo , Morfina , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores Opioides mu , MetabolismoRESUMO
OBJECTIVE@#To compare the effects of different frequency of transcutaneous electrical acupoint stimulation (TEAS) combined with wristband pressing on Neiguan (PC 6) for nausea and vomiting (PONV) after laparoscopic cholecystectomy, and optimize the TEAS frequency selection for treatment of PONV.@*METHODS@#Eighty patients undergoing laparoscopic cholecystectomy were randomly divided into a postoperative routine care group, a 2 Hz TEAS combined with wristband pressing group (2 Hz TEAS group), a 100 Hz TEAS combined with combined with wristband pressing group (100 Hz TEAS group) and a 2 Hz/100 Hz TEAS wristband pressing group (2 Hz/100 Hz TEAS group), 20 cases in each group (1 patient dropped off in the postoperative routine care group). All the four groups underwent laparoscopic cholecystectomy, and routine nursing was given after the operation. In the postoperative routine nursing group，only routine nursing was received. In the other three groups, 2 Hz TEAS combined with wristband pressing, 100 Hz TEAS combined with wristband pressing, 2 Hz/100 Hz TEAS combined with wristband pressing to simulate Neiguan (PC 6) were treated on the basis of postoperative routine care after surgery. The treatment was given for 30 min each time for a total of 4 treatments. The incidence of PONV in each group was observed at 0-2 h, 2-8 h, 8-24 h and 24-48 h after operation, and the severity of PONV and postoperative pain were evaluated.@*RESULTS@#Compared with the postoperative routine care group, the incidence and severity of PONV in the four time periods after surgery were significantly reduced in the 2 Hz/100 Hz TEAS group (all <0.05), the incidence and severity of PONV in patients at 2 h and 2-8 h after surgery were significantly reduced in the 2Hz TEAS group and the 100 Hz TEAS group (all <0.05), the postoperative pain at 8 h and 24 h after surgery was alleviated in the 100 Hz TEAS group and the 2 Hz/100 Hz TEAS group (all <0.05).@*CONCLUSION@#Different frequency of TEAS combined with wristband pressing to stimulating Neiguan (PC 6) have certain therapeutic effects on PONV in patients undergoing laparoscopic cholecystectomy. 2 Hz/100 Hz TEAS combined with wristband pressing at Neiguan (PC 6) is more effective in PONV. 2 Hz/100 Hz TEAS and 100 Hz TEAS combined with wristband pressing at Neiguan (PC 6) have postoperative analgesic effect, and 2 Hz/100 Hz TEAS has the better analgesic effect.
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Humanos , Pontos de Acupuntura , Colecistectomia Laparoscópica , Dor Pós-Operatória , Náusea e Vômito Pós-Operatórios , Terapêutica , Estimulação Elétrica Nervosa TranscutâneaRESUMO
Inflammatory Pain is one of the most common clinical symptom with unclear pathogenesis,which causes difficulty in patien's work and daily life. Previous studies have shown that P2X3 receptor participates in the pathological process of acute and chronic inflammatory pain. This paper focuses on the functions of P2X3 receptor in inflammatory pain and its relationship with TRPV1 receptor,inflammatory mediator and Epac-PKC signal transduction pathway,thereby provides a new thought for research and treatment of this disease.
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<p><b>OBJECTIVE</b>To investigate whether analgesic effect of electroacupuncture (EA) is affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia.</p><p><b>METHODS</b>There were two experiments. The experiment 1: 40 male Sprague-Dawley (SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation (SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun (BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds (PWTs) were measured before surgery (as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK (p-p38 MAPK), oxycocin-42 (OX-42, marker of microglia), and glial fibrillary acidic protein (GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn (SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide (DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole (SB203580) and EA plus SB203580 groups. SB203580 (30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above.</p><p><b>RESULTS</b>SNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats (P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH (P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs (P>0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH (P<0.01 or P<0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42 (P<0.01 or P<0.05).</p><p><b>CONCLUSIONS</b>The central mechanism of EA-induced anti-hyperalgesia may be partially associated with the reduced expression of p-p38 MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain. Therefore, EA may be a new complementary and alternative therapy for neuropathic pain.</p>
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Animais , Masculino , Biomarcadores , Metabolismo , Antígeno CD11b , Metabolismo , Eletroacupuntura , Imunofluorescência , Hiperalgesia , Patologia , Terapêutica , Imidazóis , Farmacologia , Ligadura , Microglia , Patologia , Neuroglia , Metabolismo , Fosforilação , Células do Corno Posterior , Patologia , Piridinas , Farmacologia , Ratos Sprague-Dawley , Nervos Espinhais , Patologia , Proteínas Quinases p38 Ativadas por Mitógeno , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To observe the effect of electroacupuncture (EA) on phosphorylation of spinal NR2B at Tyr 1742 site in complete Freund's adjuvant (CFA) induced inflammatory pain rats. METHods Forty male Sprague Dawley rats were randomly divided into normal group (N group, n = 10), the model group (CFA group, n = 15), and the EA group (n = 15). The inflammatory pain model was established by subcutaneous injecting CFA (0.1 mL per rat) into the right hind paw. Paw withdrawal thresholds (PWTs) were measured before CFA injection (as the base), as well as at 24 h, 25 h, 3rd day, and 7th day after CFA injection. Phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn at the 3rd day post-injection were detected using immunohistochemical assay.</p><p><b>RESULTS</b>PWTs in the CFA group were significantly lower than those of the N group at every detective time point post-injection (P < 0.01). PWTs were obviously lower in the EA group than in the N group at 24 h post-injection (P < 0.01). It showed increasing tendency, markedly higher than those of the CFA group at 25 h and 3rd day post-injection (P < 0.01). Compared with the N group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats in the CFA group was up-regulated. Compared with the CFA group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats showed a decreasing tendency in the EA group.</p><p><b>CONCLUSION</b>EA might effectively inhibit CFA-induced inflammatory pain possibly associated with down-regulating phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn.</p>
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Animais , Masculino , Ratos , Adjuvantes Farmacêuticos , Farmacologia , Eletroacupuntura , Métodos , Dor , Metabolismo , Fosforilação , Células do Corno Posterior , Metabolismo , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To observe influence of electroacupuncture (EA) on phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in spinal cord dorsal horn (SCDH) in rats with acute inflammatory pain induced by complete Freund's adjuvant (CFA), further elucidate the immediate analgesic mechanism of EA via cellular signal transduction.</p><p><b>METHODS</b>Fifty-three healthy male SD rats were divided into two batches. The inflammatory pain models of the first batch of 23 rats were established by using CFA. The changes of the paw withdrawal thresholds (PWTs) of rats were observed and positive cells of p-ERK1/2 in affected SCDH were detected by using immunohistochemistry method. The second batch of 30 rats were randomly divided into a blank control group (N group), CFA group and EA group, 10 rats in each group. The rats of CFA group and EA group were induced inflammatory pain by using CFA, and the EA group was treated with EA at 5.5 h after the model establishment. The changes of PWTs and the positive cells of p-ERK1/2 in SCDH were observed.</p><p><b>RESULTS</b>The PWTs of the first batch of rats obviously decreased at 5 h, 3 d, 7 d and 14 d after CFA administration (all P< 0.01). However, the p-ERK1/2 positive cells in affected SCDH only increased at 5 h after CFA-injection and returned to normality at 3 d after the model establishment. In the second batch, compared with that of N group at the same time point, PWTs of rats in both CFA and EA group obviously decreased after the model establishment (both P<0.01). PWTs of rats in EA group which accepted EA treatment once were longer than those before EA treatment and corresponding PWTs in CFA group at the same time point (both P<0.01). Moreover, the numbers of p-ERK1/2 positive cells of affected SCDH increased significantly in CFA group at 6 h after the model establishment (P<0.01), however, which were decreased significantly in EA group (P<0.01).</p><p><b>CONCLUSION</b>Inhibiting ERK1/2 activation of SCDH may be one of the pivotal mechanism of cellular signal transduction of the immediate analgesic effect educed by EA.</p>