RESUMEN
Upregulation of P2X3 receptor (P2X3R) has been strongly implicated in nociceptive signaling including bone cancer pain (BCP). The present study, using rat bone cancer model, aimed to explore the role of P2X3R in regulating rat pain behavior under the intervention of electroacupuncture (EA). The BCP model was successfully established by injection with MRMT-1 breast cancer cell into the medullary cavity of left tibia for 3 × 104 cells/3 µL PBS in rats as revealed by obvious bone destruction, decreased paw withdrawal thresholds (PWTs), and reduced paw withdrawal latencies (PWLs). Western blot analyses showed that P2X3R expression was significantly upregulated in ipsilateral lumbar 4-6 (L4-6) dorsal root ganglia (DRG), but the difference not seen in spinal cord dorsal horn (SCDH). With the in-depth study of P2X3R activation, we observed that intrathecal injection of P2X3R agonist α,ß-meATP aggravated MRMT-1 induced BCP, while injection of P2X3R inhibitor A-317491 alleviated pain. Subsequently, we demonstrated that BCP induced mechanical allodynia and thermal hyperalgesia were attenuated after EA treatment. Under EA treatment, total P2X3R protein expression in ipsilateral DRGs was decreased, and it is worth mentioning that decreased expression of P2X3R membrane protein, which indicated that both the expression and membrane trafficking of P2X3R were inhibited by EA. The immunofluorescence assay showed that EA stimulation exerted functions by reducing the expression of P2X3R-positive cells in ipsilateral DRGs of BCP rats. Ca2+ imaging analysis revealed that the EA stimulation decreased the percentage of α,ß-meATP responsive neurons in DRGs and inhibited calcium influx. Notably, the inhibitory effect of EA on mechanical allodynia and nociceptive flinches was abolished by intrathecal injection of α,ß-meATP. These findings demonstrated EA stimulation ameliorated mechanical allodynia and thermal hyperalgesia in rat model of MRMT-1-induced BCP. EA exerts analgesic effect on BCP by reducing the overexpression and functional activity of P2X3R in ipsilateral DRGs of BCP rats. Our work first demonstrates the critical and overall role of P2X3R in EA's analgesia against peripheral sensitization of MRMT-1-induced BCP and further supports EA as a potential therapeutic option for cancer pain in clinic.
Asunto(s)
Neoplasias Óseas , Dolor en Cáncer , Electroacupuntura , Ratas , Animales , Hiperalgesia/metabolismo , Dolor en Cáncer/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Ratas Sprague-Dawley , Electroacupuntura/métodos , Dolor/metabolismo , Neoplasias Óseas/metabolismo , Analgésicos , Ganglios Espinales/metabolismoRESUMEN
Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate), a nonspecific P2X1-7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4-L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.
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Diabetes Mellitus , Neuropatías Diabéticas , Electroacupuntura , Ratas , Animales , Hiperalgesia/metabolismo , Regulación hacia Abajo , Ganglios Espinales/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Neuropatías Diabéticas/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Diabetes Mellitus/metabolismoRESUMEN
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 (n=6), a BCP group (n=7), a MT group (n=7), a BNA+EA group (n=8) and a shame BNA group (n=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 (P<0.01). Eleven days after the operation, the PWT of the MT, BNA+EA and sham BNA groups was increased compared with the BCP group (P<0.01). Twenty-two days after the operation, the difference was no significant between the BCP group and MT group (P>0.05); the PWT of the BNA+EA group was increased compared with the MT and sham BNA group (P<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 (P<0.05, P<0.01). In the MT group, the DRG level of HDAC1 was increased compared with the BCP group (P<0.05). In the BNA+EA group, the DRG level of HDAC1 was decreased compared with the MT group and the sham BNA group (P<0.01, P<0.05), while the level of MOR was increased (P<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.
Asunto(s)
Neoplasias Óseas/complicaciones , Dolor en Cáncer/terapia , Electroacupuntura , Ganglios Espinales/metabolismo , Histona Desacetilasas/metabolismo , Receptores Opioides mu/metabolismo , Puntos de Acupuntura , Animales , Tolerancia a Medicamentos , Morfina , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To observe the expression of GABAA 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 GABAA 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 (P<0.01); 29 days after model establishment, the movement distance and staying time in the central area of open field test in the model control group were decreased significantly (P<0.05). After EA intervention, compared with the model control group and the sham EA group, the change rates of mechanical pain threshold and thermal pain threshold, as well as the movement distance and the staying time of central area were significantly increased in the EA group (P<0.01, P<0.05). Twenty-nine days after model establishment, the expression of GABAA receptor mRNA in anterior cingulate cortex and hypothalamus was not significantly different among all groups (P>0.05). Compared with the blank control group, the expression of GABAA receptor mRNA in the amygdala was decreased significantly in the model control group (P<0.01); compared with the model control group and the sham EA group, the expression of GABAA receptor mRNA in amygdala was increased after intervention in the EA group (P<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 GABAA receptor mRNA in the amygdala.
Asunto(s)
Encéfalo/metabolismo , Electroacupuntura , Inflamación/terapia , Dolor , Receptores de GABA-A/metabolismo , Puntos de Acupuntura , Amígdala del Cerebelo , Animales , Masculino , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
Protein kinase Cε (PKCε) is a transforming oncogene and plays an important role in many cellular processing. In the present paper, we review the development of experimental researches on the acute-chronic pain transformation. Results indicated that prostaglandin E2 (PGE2) / EP1 receptor-Gq-PKCε is an important signaling pathway to modulate chronic pain in peripheral dorsal root ganglion (DRG) neurons, and also plays a role in the later stage of hyperalgesia during transformation from acute to chronic pain. PKCε in DRG neurons induces mechanical and thermal hypersensitivity respectively by over expression of transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin-1 (TRPA1), further mediating the transformation from acute to chronic pain. Whereas, PGE2-evoked activation of EP1-Gq-PKCε signaling may be the key link in initiating the pain translation process through regulating downstream TRPA1 and TRPV1. Electroacupuncture (EA) has been used to effectively relieving various types of acute and chronic pain for decades, and can significantly inhibit the expression of PKCε and its upstream and downstream molecules. Therefore, it can be inferred that there exists a possibility of EA interventions in interfering the transformation from acute to chronic pain by regulating peripheral PKCε signaling pathway.
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Dolor Crónico , Electroacupuntura , Animales , Humanos , Hiperalgesia , Proteína Quinasa C-epsilon , Ratas , Ratas Sprague-Dawley , Canales Catiónicos TRPVRESUMEN
OBJECTIVE: To observe the effect of electroacupuncture (EA) on pain behavior and expression of µ-opioid receptor (MOR) and Rab5 (an important protein molecule for internalization of MOR) in the locus coeruleus (LC) region in bone cancer pain (BCP) rats with morphine tolerance (MT), so as to explore its mechanisms underlying improvement of BCP and MT. METHODS: The present study included two parts. In the first part, 23 female SD rats were randomized into sham BCP (nï¼6), BCP (nï¼9) and BCPï¼MT (nï¼8) groups, and in the second part, 61 female SD rats were randomized into 5 groups: sham BCP (nï¼11), BCP (nï¼11), BCPï¼MT (nï¼13), BCPï¼MTï¼EA (nï¼13) and BCPï¼MTï¼sham EA (nï¼13). The BCP morphine tolerance (BCPï¼MT) model was established by injection of 10 µL of human Walker 256 breast cancer cells (MRMT-1 breast cancer cells, 1 x104 cells/µL) into the bone marrow cavity at the upper part of the left tibia and intraperitoneal injection of morphine hydrochloride (10 mg/kg, once per 12 h, for 11 successive days). On day 21 after inoculation, EA (2 Hz/100 Hz, 0.5ï¼1.5 mA, increasing 0.5 mA every 10 min) was began to applied to bilateral "Zusanli" (ST30) and "Kunlun" (BL60) immediately after the first intraperitoneal injection of morphine. The treatment was performed for 30 min every time, once daily for 7 successive days. The paw withdrawal threshold (PWT) was detected before and 10, 11, 21, 22, 24, 26 and 28 days after inoculation. The immunoactivity of MOR and Rab5 proteins in the LC region was detected by immunofluorescence histochemistry. RESULTS: In the first part of the study, at the 10th day after inoculation of cancer cells, the PWT of the BCP and BCPï¼MT groups was significantly lower than that of the sham BCP group (P<0.05), suggesting a success of BCP model. From day 11 to 19 after inoculation (during injection of morphine), the PWTs of the BCPï¼MT group were significantly higher than those of the BCP group (P<0.01), and on day 21, the PWT of the BCPï¼MT group was similar to that of the BCP group (P>0.05) but significantly lower than that of the sham BCP group (P<0.01), suggesting a success of MT. Hï¼E. staining showed a large quantity of MRMT-1 cancer cells in the bone marrow cavity in both BCP and BCPï¼MT groups. In the second part of the study, the decreased PWTs from 10th to 28th day after inoculation were significantly increased on day 22, 24, 26 and 28 in the BCPï¼MTï¼EA group relevant to the BCP, BCPï¼MT and BCPï¼MTï¼sham EA groups (P<0.01). The ratios of MOR and Rab5 positive (ï¼) cells and MORï¼/Rab5ï¼ of the left LC region were significantly lower in the BCP and BCPï¼MT groups than those of the sham BCP group (P<0.01), but were considerably higher in the BCPï¼MTï¼EA group than those in the BCP, BCPï¼MT and BCPï¼MTï¼sham EA groups (P<0.01). The ratios of Rab5ï¼ and MORï¼/Rab5ï¼ cells of the BCPï¼MT group were significantly lower than those of the BCP group (P<0.05). No significant changes were found in the ratios of MORï¼ and Rab5ï¼ cells and MORï¼/Rab5ï¼ cells after BCPï¼MTï¼sham EA in comparison with the BCPï¼MT group (P>0.05). CONCLUSION: EA intervention can relieve pain and MT in bone cancer pain rats with MT, which may be related to its effects in increasing MOR expression and promoting endocytosis of MOR in LC region.
Asunto(s)
Dolor en Cáncer , Electroacupuntura , Animales , Línea Celular Tumoral , Endocitosis , Femenino , Humanos , Locus Coeruleus , Morfina , Ratas , Ratas Sprague-DawleyRESUMEN
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 groupï¼only 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 P<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 P<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 P<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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Colecistectomía Laparoscópica , Náusea y Vómito Posoperatorios/terapia , Estimulación Eléctrica Transcutánea del Nervio , Puntos de Acupuntura , Humanos , Dolor PostoperatorioRESUMEN
OBJECTIVE: To observe the effect of electroacupuncture (EA)on mechanical pain transition and content of protein kinase C epsilon(PKCε)in dorsal root ganglia (DRG) in inflammatory articular pain ratsï¼so as to explore its peripheral mechanism underlying relieving transition from acute to chronic pain. METHODS: 1)In the first part of the present studyï¼male SD rats were equally randomized into blank controlï¼sham hyperalgesic priming(HP), and real HP groups(nï¼6 in each). The HP model was established by subcutaneous injection of 1% carrageenan (100 µL) into the left hind paw (the first injection)ï¼followed by injection of PGE 2 (100 ng/25 µL, the second injection) into the dorsum pedis of the same hind paw 7 days after the first injection. The mechanical withdrawal threshold (MWT) of the ipsilateral paw was detected before and 4, 24, 48, 72 h, and 7 d after the first injectionï¼and 1, 4, 24 and 48 h after the second injection. 2) In the second partï¼SD rats were randomly divided into sham-HPï¼real HPï¼sham-EA and EA groups(nï¼6 in each). The sham-HP and HP models were made in the same way as those in the first part. Bilateral "Zusanli"(ST 36)and "Kunlun"(BL 60)were punctured with filiform needles and also stimulated with electrical currentï¼2 Hz/100 Hzï¼0.5ï¼1.5 mA(0.5 mA increase per 10 min)for 30 minï¼1 time/d from the 1st carrageenan injection on till the end of the experiments. PKCε protein expression in the L 4ï¼L 6 DRGs was assayed by Western blot 48 h after the second injection. RESULTS: 1)In the first part of the studyï¼compared with the sham-HP groupï¼the MWT at 4, 24ã48 h after carrageenan injection and 4, 24 and 48 h after PGE 2 injection were significantly decreased in the HP model group(P<0.01). 2)In the second partï¼compared with the HP groupï¼the MWT at 24ã48 and 72 h after carrageenan injection, and 24 and 48 h after PGE 2 injection were significantly up-regulated in the EA group(P<0.05ï¼P<0.01). 3)The relative content of PKCε in the DRGs(L 4ï¼L 6)was significantly higher in the HP group than in the sham-HP group(P<0.01)ï¼but considerably lower in the EA group than in the HP group (P<0.01)ï¼. CONCLUSION: EA has a good effect on pain conversion in inflammatory joint pain ratsï¼which may be related to its effect in down-regulating the PKCε level in the ipsilateral lumbar DRGs.
Asunto(s)
Electroacupuntura , Puntos de Acupuntura , Animales , Ganglios Espinales , Hiperalgesia , Masculino , Proteína Quinasa C-epsilon , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To observe the effect of electroacupuncture (EA) on mechanical hyperalgesia threshold (MHTs) and thermal hyperalgesia threshold (THTs) and content of proteinase-activated receptors 2 (PAR 2) in dorsal root ganglia (DRG) in rats with inflammatory pain, so as to explore its peripheral mechanism underlying improvement of inflammatory pain. METHODS: The present study contains two parts. 1) In the first part, 27 male SD rats were randomized into sham hyperalgesic priming (sham-HP) group and real hyperalgesic priming (HP) group (nï¼5 in the sham-HP group and nï¼6 in the HP group for the test of MHTs, nï¼8 in the two groups for the test of THTs). The sham-HP model was established by subcutaneous injection of normal saline into the left plantar part of the hind-paw, and the HP model established by subcutaneous injection of 1% carragenan (the first injection) into the same left hind paw, followed by injection of PGE2 (100 ng/25 µL, the second injection) into the dorsum pedis of the same hind paw 7 days after the first injection. The ipsilateral paw withdrawal latencies (MHTs and THTs) were detected before and 5 h, 3 d and 6 d after the first injection, 0.5, 4 and 24 h after the second injection. 2) In the second part, 64 male SD rats were randomly divided into sham-HP, HP, sham-EA and EA groups (nï¼16 in each group). The sham-HP and HP models were made in the same way as the first part. Both"Zusanli"(ST 36)and "Kunlun"(BL 60) were punctured with filiform needles in the sham-EA group and also stimulated with EA: 2 Hz/100 Hz, 0.5ï¼1.5 mA (0.5 mA increase per 10 min) for 30 min in the EA group, 1 time/d for 7 d. Both ipsilateral MHTs and THTs were observed at the same time-points of the first part and the PAR 2 protein content in the L 4ï¼L 6 DRGs was assayed by ELISA 24 h after the second injection. RESULTS: 1) In the first part of the study, compared with the sham-HP group, the MHTs at 5 h and 3 d, and THT at 5 h after the first injection, and MHTs, and THTs at 4 and 24 h after the se-cond injection were significantly decreased in the HP group (P<0.01, P<0.05). 2) In the second part of the study, compared with the HP group, the MHTs at 4 and 24 h after the second injection and the THTs at 3 d after the first injection, 4 and 24 h after the second injection were significantly up-regulated in the EA group (P<0.01, P<0.05). The content of PAR 2 in the DRGs (L 4ï¼L 6) was significantly higher in the HP group than in the sham-HP group (P<0.05), but considerably lower in the EA group than in the HP group (P<0.05). CONCLUSION: EA can suppress hyperalgesia priming in inflammatory pain rats which may be related to its effect in down-regulating PAR 2 level in the lumbar DRGs.
Asunto(s)
Electroacupuntura , Hiperalgesia , Animales , Ganglios Espinales , Masculino , Dolor , Ratas , Ratas Sprague-Dawley , Receptor PAR-2RESUMEN
HYPOTHESIS: Electroacupuncture (EA) has been used as an alternative analgesic therapy for hundreds of years, yet its analgesic potency and therapeutic advantage against bone cancer pain (BCP) in comparison with morphine remains unclear. This study aimed to investigate the effects of EA on mechanical allodynia and cellular immunity of BCP rats, and to further explore the potential mechanism. METHODS: The BCP model was established by implanting Walker 256 mammary gland carcinoma cells into the left tibia of adult female Sprague-Dawley rats. EA (dilatational wave, 2/100 Hz, 0.5 mA-1mA-1.5 mA for 10 minutes each intensity) was applied bilaterally to Zusanli (ST 36) and Kunlun (BL 60) for 30 minutes. Both EA stimulation and morphine (10 mg/kg, intraperitoneally) was given once every other day. Naloxone (0.3 mg/kg, intraperitoneally) was injected at 30 minutes prior to EA. Mechanical allodynia were demonstrated by paw withdrawal thresholds (PWTs) which measured by dynamic plantar aesthesiometer. T cell proliferation, percentage of CD3+, CD4+ and CD8+ T lymphocytes in spleen as well as expression of interleukin-2 (IL-2) in plasma were detected by WST-8, flow cytometry, and enzyme-linked immunosorbent assay technique, respectively. RESULTS: An intratibial inoculation of Walker 256 mammary gland carcinoma cells significantly decreased PWTs to mechanical stimuli. EA stimulation alleviated mechanical allodynia in BCP rats, and the analgesic potency of EA was weaker than that of morphine. In contrast to morphine, EA stimulation of BCP rats increased splenic concanavalin A (Con A)-induced T cell proliferation and plasma IL-2 content, as well as increased the percentages of splenic CD3+CD4+ and CD3+CD8+ T cell subsets. Moreover, both the analgesic effect and the partial immunomodulation of EA were suppressed by an intraperitoneal injection of naloxone. CONCLUSION: EA could significantly alleviate BCP-induced mechanical allodynia. Although the analgesic effect of EA was weaker than that of morphine, EA had an immunomodulation effect on cellular immunity. Both analgesic and immunomodulatory effect of EA might share the same mechanism via the opioid-mediated pathway, which needs further investigation.
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Neoplasias Óseas/inmunología , Dolor en Cáncer/inmunología , Hiperalgesia/inmunología , Inmunidad Celular/inmunología , Animales , Complejo CD3/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Proliferación Celular/fisiología , Electroacupuntura/métodos , Femenino , Humanos , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The effect of electroacupuncture (EA) is affected by both the acupuncture point selection and the frequency of stimulation. However, little is known regarding acupuncture point and simulation frequency selection. Neuronal activation of the nucleus of the solitary tract (NTS) is one of the important targets of EA for modulating gastrointestinal function. This study investigated the effects of various combinations of EA frequencies and acupuncture points on NTS neurons. METHODS: Rats were randomly divided into normal, 2 Hz EA, 100 Hz EA and the alternate 2/100 Hz EA groups. Then rats in each group were randomly divided into the following two subgroups according to the acupuncture point: ST 36 group and ST 25 group. All the rats underwent electrode implantation surgery. Rats in all EA groups received one treatment with EA (a constant square wave at, 2 Hz,100 Hz or 2/100 Hz frequencies with intensities ranging from 1 to 2 mA), and NTS neuronal activation was recorded before and after EA treatment. Finally, to confirm the effect of EA on the NTS, minimal acupuncture was administered and its effect on NTS was detected. RESULTS: ST 36 stimulated with 2 Hz EA significantly increased the population of excited NTS neurons and spike frequency. However, ST 36 stimulated with 100 Hz or 2/100 Hz EA produced only a transient effect on the activity of NTS neurons and did not induce any effect on the spike frequency. Furthermore, the excitatory effect of 100 Hz or 2/100 Hz EA on NTS neurons in the ST 36 group was lower than 2 Hz EA at the same point. When applied to ST 25, 2 Hz EA had no significant excitatory effect on NTS neurons or spike frequency. However, 100 Hz EA or 2/100 Hz EA at ST 25 decreased both NTS neuronal excitability and spike frequency. By comparing the effects of different EA combinations, it was shown 2 Hz EA applied to ST 36 had the strongest excitatory effect on NTS neurons, while 100 Hz EA applied to ST 25 had the greatest inhibitory effect. Minimal acupuncture stimulation produced no effect on NTS neurons. CONCLUSION: EA's effects on NTS were mainly affected by the acupuncture point selection, but the frequency of EA also played a role. Different combinations of acupuncture points and frequency selection may lead to different EA effects on NTS neuronal excitability.
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Puntos de Acupuntura , Electroacupuntura , Núcleo Solitario/fisiología , Animales , Masculino , Neuronas/fisiología , Ratas , Ratas Sprague-Dawley , Núcleo Solitario/citologíaRESUMEN
Postoperative ileus (POI) after abdominal surgery significantly lowers the life quality of patients and increase hospital costs. However, few treatment strategies have successfully shortened the duration of POI. Electroacupuncture (EA) is a modern way of administering acupuncture and widely used in various gastrointestinal (GI) diseases in the world. Here, we studied the effect of EA on POI and its underlying mechanisms. Intestinal manipulation resulted in significant delays of GI transit, colonic transit and gastric emptying. Surgery also up-regulated c-fos in nucleus of the solitary tract (NTS) and induced inflammation response in the small intestine. Further, operation and inhale anesthesia inhibited NTS neuron excitation duration for the whole observation time. EA administered at ST36 indeed shortened the recovery time of GI and colonic transit, and significantly increased the gastric emptying. EA also significantly activated the NTS neurons after operation. However, there was no anti-inflammation effect of EA during the whole experiment. Finally, atropine blocked the regulatory effect of EA on GI function, when it was injected after surgery, but not before surgery. Thus, the regulatory effect of EA on POI was mainly mediated by exciting NTS neurons to improve the GI tract transit function but not by activating cholinergic anti-inflammatory pathway.
Asunto(s)
Electroacupuntura , Ileus/terapia , Nervio Vago/metabolismo , Abdomen/cirugía , Animales , Atropina/farmacología , Electrodos Implantados , Vaciamiento Gástrico/efectos de los fármacos , Tránsito Gastrointestinal/efectos de los fármacos , Ileus/etiología , Ileus/patología , Inflamación , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Intestino Delgado/inmunología , Intestino Delgado/fisiología , Leucocitos/citología , Leucocitos/inmunología , Complicaciones Posoperatorias , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Núcleo Solitario/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To investigate whether analgesic effect of electroacupuncture (EA) is affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Asunto(s)
Electroacupuntura , Microglía/enzimología , Microglía/patología , Nervios Espinales/patología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Biomarcadores/metabolismo , Antígeno CD11b/metabolismo , Técnica del Anticuerpo Fluorescente , Hiperalgesia/patología , Hiperalgesia/terapia , Imidazoles/farmacología , Ligadura , Masculino , Microglía/efectos de los fármacos , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Fosforilación/efectos de los fármacos , Células del Asta Posterior/efectos de los fármacos , Células del Asta Posterior/enzimología , Células del Asta Posterior/patología , Piridinas/farmacología , Ratas Sprague-Dawley , Nervios Espinales/efectos de los fármacosRESUMEN
Persistent neuropathic pain is associated with anxiety. The phosphorylation of extracellular signal-regulated kinase (p-ERK) in the anterior cingulate cortex (ACC) plays an important role in pain-induced anxiety. Acupuncture is widely used for pain and anxiety. However, little is known about which acupuncture technique is optimal on pain-induced anxiety and the relationship between acupuncture effect and p-ERK. The rat model was induced by L5 spinal nerve ligation (SNL). Male adult SD rats were randomly divided into control, SNL, strong manual acupuncture (sMA), mild manual acupuncture (mMA), and electroacupuncture (EA) group. Bilateral "Huantiao" (GB 30) were stimulated by sMA, mMA, and EA, respectively. The pain withdrawal thresholds (PWTs) and anxiety behavior were measured, and p-ERK protein expression and immunoreactivity cells in ACC were detected. PWTs increased significantly in both sMA and EA groups. Meanwhile, anxiety-like behavior was improved significantly in the sMA and mMA groups. Furthermore, the overexpression of p-ERK induced by SNL was downregulated by strong and mild manual acupuncture. Therefore, strong manual acupuncture on bilateral "Huantiao" (GB 30) could be a proper therapy relieving both pain and pain-induced anxiety. The effect of different acupuncture techniques on pain-induced anxiety may arise from the regulation of p-ERK in ACC.
RESUMEN
BACKGROUND: Activation of extracellular signal-regulated kinase1/2 (ERK1/2) in dorsal horn of the spinal cord by peripheral inflammation is contributed to inflammatory pain hypersensitivity. Although electroacupuncture (EA) has been widely used to alleviate various kinds of pain, the underlying mechanism of EA analgesia requires further investigation. This study investigated the relationship between EA-induced analgesia and ERK signaling involved in pain hypersensitivity. METHODS: The rats were randomly divided into control, model, EA and sham EA groups. Inflammatory pain model was induced by injecting of 100 µl Complete Freund's adjuvant (CFA) into the plantar surface of a hind paw. Rats in the EA group were treatment with EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1-2 mA) at 5.5 h, 24.5 h and 48.5 h. Paw withdrawal thresholds (PWTs) were measured before modeling and at 5 h, 6 h, 25 h and 49 h after CFA injection. Rats were killed and ipsilateral side of the lumbar spinal cords were harvested for detecting the expressions of p-ERK1/2, Elk1, COX-2, NK-1 and CREB by immunohistochemistry, real-time PCR, western blot analysis and EMSA. Finally, the analgesic effect of EA plus U0126, a MEK (ERK kinase) inhibitor, on CFA rats was examined. RESULTS: Inflammatory pain was induced in rats by hindpaw injection of CFA and significantly increased phospho-ERK1/2 positive cells and protein levels of p-ERK1/2 in the ipsilateral spinal cord dorsal horn (SCDH). CFA up-regulated of cyclooxygenase-2 (COX-2) mRNA and protein expression at 6 h after injection and neurokinin-1 receptor (NK-1) expression at 49 h post-injection, in the SCDH. EA, applied to Zusanli (ST36) and Kunlun (BL60), remarkably increased the pain thresholds of CFA injected rats, significantly suppressed ERK1/2 activation and COX-2 protein expression after a single treatment, and decreased NK-1 mRNA and protein expression at 49 h. EA decreased the DNA binding activity of cAMP response element binding protein (CREB), a downstream transcription factor of ERK1/2, at 49 h after CFA injection. Moreover, EA and U0126 synergistically inhibited CFA-induced allodynia. CONCLUSIONS: The present study suggests that EA produces analgesic effect by preventing the activation of ERK1/2-COX-2 pathway and ERK1/2-CREB-NK-1 pathway in CFA rats.
Asunto(s)
Electroacupuntura/métodos , Sistema de Señalización de MAP Quinasas , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Manejo del Dolor/métodos , Médula Espinal/fisiología , Animales , Butadienos/farmacología , Hiperalgesia/inducido químicamente , Hiperalgesia/terapia , Masculino , Nitrilos/farmacología , Dolor/enzimología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Médula Espinal/enzimologíaRESUMEN
BACKGROUND: Electroacupuncture (EA) has a substantial analgesic effect on inflammatory pain induced by complete Freund's adjuvant (CFA). The activation of the c-Jun N-terminal kinase 1/2 (JNK1/2) signal transduction pathway in the spinal cord is associated with inflammatory pain. However, the relationship between EA's analgesic effect and the JNK1/2 signal transduction pathway in the inflammatory pain remain unclear. In the present study, we used the established rat model of CFA-induced inflammatory pain to investigate the role of the spinal JNK1/2 pathway in EA-mediated analgesia. RESULTS: We observed a decrease in paw withdrawal thresholds and an increase in paw edema at 1 and 3 days after injecting CFA into the right hindpaw. CFA, 3 days after injection, upregulated expression of phospho-c-Jun N-terminal kinase1/2 (p-JNK1/2) protein and its downstream targets, the transcriptional regulators p-c-Jun and activator protein-1 (AP-1), as well as cyclooxygenase-2 (COX-2) and the transient receptor potential vanilloid 1 (TRPV1). EA significantly alleviated CFA-induced inflammatory pain. In addition, EA reduced p-JNK1/2 protein levels and COX-2 mRNA expressions, a degree of down-regulated p-c-Jun protein level and AP-1 DNA binding activity in the spinal dorsal horn of CFA-administered animals, but it had no effect on TRPV1 mRNA expression. Furthermore, EA and the JNK inhibitor SP600125 synergistically inhibited CFA-induced hyperalgesia and suppressed the COX-2 mRNA expression in the spinal dorsal horn. CONCLUSIONS: Our findings indicate that EA alleviates inflammatory pain behavior, at least in part, by reducing COX-2 expression in the spinal cord via the JNK1/2 signaling pathway. Inactivation of the spinal JNK1/2 signal transduction pathway maybe the potential mechanism of EA's antinociception in the inflammatory pain model.
Asunto(s)
Electroacupuntura , Inflamación/enzimología , Sistema de Señalización de MAP Quinasas , Dolor/enzimología , Dolor/prevención & control , Animales , Modelos Animales de Enfermedad , Adyuvante de Freund , Hiperalgesia/prevención & control , Inflamación/inducido químicamente , Masculino , Proteína Quinasa 8 Activada por Mitógenos/metabolismo , Proteína Quinasa 9 Activada por Mitógenos/metabolismo , Dolor/inducido químicamente , Umbral del Dolor , Fosforilación , Ratas , Ratas Sprague-Dawley , Médula Espinal/enzimologíaRESUMEN
OBJECTIVE: To observe the effect of different intensities of manual acupuncture (MA) stimulation on mechanical pain thresholds (PTs) and the expression of phosphorylated extracellular signal-regulated kinases (p-ERK) in lumbar spinal dorsal horn regions in rats with neuropathic mirror-image pain, so as to explore its mechanisms underlying analgesia. METHODS: Forty male SD rats were equally and randomly divided into control, spinal nerve ligation (SNL) model, mild MA-stimulation, and strong MA-stimulation groups. Neuropathological pain model was established by ligature of the spinal nerve (L 5). Three days after the SNL, bilateral "Huantiao" (GB 30) were stimulated by rotating the thin (0.22 mm x 13 mm) or thick (0.3 mm x 13 mm) filiform needles at a frequencies of 60 times/min or 180 times/min and at an angle of 180 degrees or 360 degrees for 2 min for rats in the mild and strong MA-stimulation groups, respectively, followed by remaining the needle in place for 30 min. The mechanical PTs were measured before and after SNL. The expression of p-ERK protein in bilateral dorsal horn regions of the lumbar spinal cord (L4- L 6) was detected by Western blot. RESULTS: In comparison with the control group, the mechanical PTs were significantly decreased beginning from the 3rd day on after SNL on the affected side and from the 7th day on after SNL on the healthy hindpaw (P < 0.05), simultaneously, p-ERK protein expression levels of dorsal horn regions on both sides of the spinal cord were considerably up-regulated on the 12th day (P < 0.05). Compared with the model group, the PTs of the affected hindpaw and the healthy hindpaw were significantly increased on the 7th and 12th day in the strong MA-stimulation group (P < 0.05, P < 0.01), whereas pERK expression levels in the bilateral spinal dorsal horn regions were obviously down-regulated in the strong MA-stimulation group (P < 0.05). No significant differences were found between the model and mild MA-stimulation groups in the PTs of bilateral hindpaws and p-ERK expression levels of the bilateral spinal dorsal horn regions (P > 0.05) except the PTs of the healthy hindpaw on 7th day (P < 0.05). CONCLUSION: Strong MA-stimulation can alleviate neuropathic mirror-image pain in SNL rats, which is closely related to its effect in down-regulating the expression of p-ERK in the bilateral spinal dorsal horn regions.
Asunto(s)
Puntos de Acupuntura , Terapia por Acupuntura/métodos , Dolor de Espalda/terapia , Quinasas MAP Reguladas por Señal Extracelular/genética , Neuralgia/terapia , Células del Asta Posterior/enzimología , Terapia por Acupuntura/instrumentación , Animales , Dolor de Espalda/enzimología , Dolor de Espalda/genética , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Masculino , Neuralgia/enzimología , Neuralgia/genética , Umbral del Dolor , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. METHODS: Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 µl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. RESULTS: CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. CONCLUSIONS: TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway.
Asunto(s)
Analgesia , Ciclooxigenasa 2/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hiperalgesia/terapia , Dolor/patología , Médula Espinal/metabolismo , Estimulación Eléctrica Transcutánea del Nervio , Animales , Ciclooxigenasa 2/genética , Dinoprostona/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/genética , Adyuvante de Freund , Hiperalgesia/inducido químicamente , Hiperalgesia/metabolismo , Inflamación/complicaciones , Inflamación/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Dolor/inducido químicamente , Dolor/metabolismo , Umbral del Dolor , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. RESULTS: EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat's paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. CONCLUSIONS: The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats.
Asunto(s)
Factor de Transcripción Activador 2/metabolismo , Electroacupuntura , Inflamación/enzimología , Dolor/enzimología , Columna Vertebral/enzimología , Canales Catiónicos TRPV/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Analgesia , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Conducta Animal/efectos de los fármacos , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Activación Enzimática/efectos de los fármacos , Adyuvante de Freund , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/patología , Inflamación/terapia , Masculino , Dolor/tratamiento farmacológico , Dolor/patología , Fosforilación/efectos de los fármacos , Células del Asta Posterior/efectos de los fármacos , Células del Asta Posterior/enzimología , Células del Asta Posterior/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Columna Vertebral/patología , Canales Catiónicos TRPV/genética , Factores de TiempoRESUMEN
OBJECTIVE: 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. RESULTS: 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. CONCLUSION: 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.