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Objective To detect the role of PAR2-PKA/PKCε signaling pathway in periphery neurons in the tran-sition from acute to chronic pain,and investigate the possible approach to prevent both acute and chronic pain simultane-ously. Methods SD rats were randomly divided into control group,sham model group,model group,iPAR2-1 group and iPAR2-2 group. The hyperalgesia priming model was established by injection of carrageenan and PGE2 into the left hind-paw except control and sham model group. PGE2 was administrated at 7 days after carrageenan injection. The PAR2 inhibi-tor was administrated before and after PGE2 injection separately in the iPAR2-1 group and iPAR2-2 group. The paw with-drawal thresholds(PWTs)of rats in each group was detected before and at 5 h,3 d,6 d,7 d 0.5 h,7 d 4 h,7 d 24 h after carrageenan injection. The expression level of PAR2, PKA and PKCε proteins in the dorsal root ganglion(DRG) were detected at 24 h after carrageenan injection. Results The hyperalgesia priming model was successfully generated. When PGE2 was administrated at 7 days after carrageenan injection, the hyperalgesia induced by PGE2 was significantly prolonged. The PWTs of rats in the model group were significantly lower than that of the control and sham model groups(P<0.01),though the PWTs of sham model group had no significant difference with the control on 7 d 24 h after carrageenan injection(P>0.05). The expression level of PAR2 and PKCε in the ipsilateral DRG neurons were significantly increased on 7 d 24 h after carrageenan injection,when compared with the control and sham model groups(P<0.05). PAR2 inhibi-tor prevented the prolonged hyperalgesia induced by PGE2(P<0.05)and decreased the PKCε expression in DRG neurons whenever it was given(P<0.05). However,PAR2 inhibitor did not regulate the acute inflammatory pain of PGE2 and the expression of PKA in DRG neurons(P>0.05). Conclusions Inhibition of the expression of PAR2 can prevent the tran-sition from acute to chronic pain. This effect may be related with the inhibitory effect on the activation of PAR2-PKCε sig-naling pathway in DRG neurons. However,inhibition of PAR2 can not regulate the acute pain. These may because of that the PAR2-PKA signaling pathway does not play a role in acute pain.
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Neuropathic pain is a chronic pain caused by primary nervous system damage and nerve dysfunction. Its pathogenesis is complex and diverse. It is difficult to treat clinically. In recent years, researchers used electroacupuncture to treat neuropathic pain and obtained a desirable effect. This article summarizes recent years’ studies on the main mechanisms of neuropathic pain and the intervention effect of electroacupuncture to provide reference for following studies on electroacupuncture treatment of neuropathic pain.
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<p><b>OBJECTIVE</b>To observe the intervention effect of electroacupuncture (EA) on small intestinal motility in the rats of postoperative ileus (POI) at perioperative stage and explore the mechanism on the regulation of interstitial cells of Cajal (ICC) in the treatment of POI.</p><p><b>METHODS</b>Sixty heathy male SD rats were randomized into a sham-operation group, a model group, an EA group and a sham-EA group, 15 rats in each one. Except the sham-operation group, POI modeling was done in the rest groups. In the EA group, separately, 48 h, 24 h and 0.5 h before modeling, during modeling and 6 h, 12 h and 24 h after modeling, EA was given bilaterally to "Zusanli" (ST 36), 5 Hz, 1-2 mA, for 30 min. The sham-EA stimulation was given in the sham-EA group at the same time points. The same fixation was the only intervention in the model group. No intervention was applied in the sham-operation group. Five rats were selected randomly from each group 6 h, 12 h and 24 h after modeling for the determination of small intestine motility and they were sacrificed. Afterwards, the small intestinal muscular layer was collected for the determination of c-kit and P2X7 mRNA. In 24 h of modeling, the immunofluorescence test was done for c-kit determination.</p><p><b>RESULTS</b>In 6 h, 12 h and 24 h of modeling, in the model group, the EA groupand the sham-EA group, the small intestine motility was apparently lower than that in the sham-operation group at the same time points (all<0.01). In 6 h and 12 h of modeling, the small intestine motility in the EA group was not different significantly as compared with that in the model group (both>0.05). In 24 h of modeling, the small intestine motility in the EA group was better than that in the model group and the sham-EA group at the same time points (both<0.05). The difference was not significant between the sham-EA group and the model group (>0.05). In 6 h, 12 h and 24 h of modeling, c-kit mRNA expression of small intestine muscular layer was reduced apparently in the model group (all<0.01) and P2X7 mRNA expression did not change apparently (all>0.05). In 24 h of modeling, as compared with the model group and the sham-EA group, c-kit mRNA expression and positive cell area in the small intestine muscular layer were increased in the EA group (all<0.01).</p><p><b>CONCLUSIONS</b>EA effectively increases the small intestinal motility in POI rats, shortens the recovery time, which is probably closely relevant with the increase of ICC count in small intestinal muscular layer.</p>
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<p><b>OBJECTIVE</b>To observe the effects of electroacupuncture (EA) on pain behavior in rats with bone cancer pain and morphine tolerance, and to explore partial action mechanism.</p><p><b>METHODS</b>Forty-two SD healthy female rats were randomly divided into a sham operation group (7 rats), a bone cancer pain group (8 rats), a morphine tolerance group (9 rats), an EA group (9 rats) and a sham EA group (9 rats). The rats in the sham operation group were treated with injection of phosphate buffer saline at medullary cavity of left-side tibia, and the rats in the remaining groups were injected with MRMT-1 breast cancer cells. After operation, no treatment was given to rats in the sham operation group and bone cancer pain group. 11 days after operation, rats in the morphine tole-rance group, EA group and sham EA group were treated with intraperitoneal injection of morphine hydrochloride, once every 12 hours, for 11 days to establish the model of bone cancer pain and morphine tolerance. One day after the establishment of this bone cancer pain model, the rats in the morphine tolerance group were injected with morphine, once every 12 hours (9:00 a.m. and 9:00 p.m.) for 7 days; the rats in the EA group and sham EA group were injected with morphine at 9:00 a.m., and treated with EA (2 Hz/100 Hz) and sham EA (only injected into the subcutaneous tissue) at bilateral "Zusanli" (ST 36) and "Kunlun" (BL 60), 30 min per treatment, once a day for 7 days. One day before cancer cell injection, 6 days, 8 days, 10 days after operation, after 30 min on 1 days, 5 days, 9 days, 11 days of morphine injection, and after 30 min on 1 days, 3 days, 5 days, 7 days of EA treatment, the paw withdrawal threshold (PWT) was measured in each group. On 11 day of morphine injection, HE staining was applied to observe the morphology and structure change of tibia in the sham operation group, bone cancer pain group and morphine tolerance group, random 2 rats in each group. On 7 days of EA treatment, fluorescent immunohistochemical method was applied to observe the expression of μ-opioid receptor positive cells in nucleus ceruleus in each group, random 4 rats in each one.</p><p><b>RESULTS</b>After 10 days of the cancer cells injection, the PWT of 28 rats of bone cancer pain model (8 rats in the bone cancer pain group, 8 rats in the morphine tolerance group, 6 rats in the EA group and 6 rats in the sham EA group) was significantly lower than that of 7 rats in the sham operation group (<0.01). After one day of morphine injection, the PWT of the morphine tolerance group, EA group and sham EA group was higher than that of the bone cancer pain group (all<0.01); on 11 d of morphine injection, the PWT of the morphine tolerance group, EA group and sham EA group was not significantly different from that of the bone cancer pain group (all>0.05). On 11 d of morphine injection, the tumor induced by cancer cells was observed in upper 1/3 tibia in the bone cancer pain group and morphine tolerance group, and the marrow cavity was filled with MRMT-1 cancer cells; no abnormal change was observed in the sham operation group. On 1 d, 3 d, 5 d and 7 d of EA treatment, the PWT of the cancer pain group, morphine tolerance group and sham EA group was lower than that of the EA group (all<0.01). On 7 d of EA treatment, the positive expression of MOR in nucleus ceruleus in the cancer pain group, morphine tolerance group, EA group and sham EA group was lower than that in the sham operation group (<0.01,<0.05), and that in the cancer pain group, morphine tolerance group and sham EA group was lower than that in the EA group (all<0.01).</p><p><b>CONCLUSIONS</b>EA can improve mechanical pain threshold in rats with bone cancer pain-morphine tolerance, and improve the abnormal pain, which is likely to be involved with improvement of the MOR positive cells expression in nucleus ceruleus by EA.</p>
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Postoperative ileus (POI) is a common abdominal postoperative complication of surgery as well as obstetrics and gynecology. There is a lack of an effective method of modern medicine due to its complex pathophysiological mechanism and the postoperative physiological disorder of patient. Acupuncture has remarkable regulatory effects on gastrointestinal function. Some clinical studies indicated that acupuncture was an effective method to treat POI, which could reduce the duration of POI and the treatment costs of patients in hospital. However, the mechanism and law of acupuncture on treating POI is still unclear. Some clinical studies indicated that the regulatory effect of acupuncture on the gastrointestinal motility was associated with its regulation of the autonomic nerve system and immune system. Based on its effect on regulating autonomic nerve system and immune system, acupuncture would be a potential and safe treatment for POI.
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<p><b>OBJECTIVE</b>To observe the intervention of electroacupuncture (EA) with different current frequencies and treatment frequencies on pain thresholt in rats with bone-cancer pain, so as to optimize treatment parameters of EA against bone cancer pain; and by measuring gene expression of opioid receptor and precursor in different tissues to preliminarily explore the possible mechanism of EA against bone cancer pain.</p><p><b>METHODS</b>Ninety healthy female SD rats were randomly divided into a control group, a model group, EA groups (6 subgroups according to different frequencies) and a sham EA group, ten rats in each one. Rats in the control group were injected with 10 µL of amicrobic phosphate buffer solution (PBS) into tibial cavity; rats in the remaining groups were injected with Walker 256 cancer cells to establish model of bone-cancer pain. No treatment was given to rats in the control group and model group; rats in the EA groups were treated with EA at bilateral "Housanli" (ST 36) and "Genduan" with 3 different current frequencies (2 Hz, 100 Hz and 2 Hz/100 Hz), once a day and once every other day, 30 min per treatment (1mA for 15 min, 2 mA for 15 min); rats in the sham EA group were treated with identical acupoints as the EA group, but the acupoints were needled subcutaneously and EA was connected with power off. All the treatment was given for 14 days. Dynamic plantar aesthesiometer was applied to measure the paw withdrawal thresholds (PWTs) of the affected side before the model establishment, 6d, 8d, 10d, 12d, 14d, 16d, 18d, and 20d after model establishment. The mRNA expressions of µ-opioid receptor (MOR), κ-opioid receptor (KOR), δ-opioid receptor (DOR), proopiomelanocortin (POMC) and prodynorphin (PDYN) in dorsal root ganglion (DRG) and lumbar spinal cord dorsal horn (SCDH) of L4-L6 of the affected side were detected by PCR method.</p><p><b>RESULTS</b>There were no differences in PWTs among all groups before model establishment (P>0. 05). Each time point after model establishment, PWTs in model group were obviously lower than those in the control group (all P<0. 01). Compared with the model group, PWTs in each EA subgroup were all increased (all P<0.05), but the differences at different time points were not significant among EA subgroups (P>0.05). The mRNA expressions of MOR, KOR, POMC, and PDYN in L4-L6 DRG in the 2 Hz/100 Hz II group were significantly higher than those in model group (P<0. 05, P<0. 01), while the mRNA expressions of MOR, KOR, DOR, POMC and PDYN in SCDH were not different compared with the model group (P>0. 05).</p><p><b>CONCLUSION</b>EA treatment has obvious analgesic effect on bone-cancer pain, however, its effect is not related with current frequency and treating frequency. EA against bone-cancer pain may be related with increasing the mRNA expression of some peripheral opioid receptors and precursor.</p>
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Animais , Feminino , Humanos , Ratos , Analgesia por Acupuntura , Métodos , Pontos de Acupuntura , Neoplasias Ósseas , Eletroacupuntura , Métodos , Encefalinas , Metabolismo , Gânglios Espinais , Metabolismo , Dor , Genética , Metabolismo , Manejo da Dor , Métodos , Precursores de Proteínas , Metabolismo , Ratos Sprague-Dawley , Receptores Opioides , Genética , MetabolismoRESUMO
Objective To observe the functional changes of T lymphocytes in the spleen of rats with bone cancer pain.Methods forty-one healthy female Sprague-Dawley rats were used in this study, and were divided into blank control, PBS and Walker-256 tumor groups.Bone cancer pain model was established by inoculation of Walker 256 cancer cells into the tibial cavity.The paw withdrawal threshold (PWT), paw withdrawal thermal latency (PWL), and spontaneous pain (SP) were all measured before modelling (as base) and at 4, 6, 8, 10, 12, 14, 16, 18, and 20 days after modelling. The function of T lymphocyte proliferation, and the content of T lymphocytes and their subgroups in the spleen were detected by cell counting kit-8 method and flow cytometry, respectively, on day 20 after modelling.Results Before modellng, there were no differences of PWT, PWL, and SP between the PBS and model groups.After modelling, the PWT and SP of model group were significantly decreased on day 4, and were always lower than that of PBS group during the experiment.Statistical analysis revealed that Walker-256 cancer cell inoculation in the tibia induced a significant decrease in PWL on day 8, 10 and 12 after modellng.Compared with the control group, T lymphocyte proliferation, content of T lymphocyte (CD3) and subgroups ( CD4 and CD8) in the PBS group were not significantly decreased.However, T lymphocyte proliferation and the content of CD3 lymphocytes in the model group were significantly lower than those in the blank control group and/or PBS group.Conclusions The bone cancer pain rat model may appear obvious mechanical allodynia and spontaneous pain.Its thermal pain hyperalgesiaonly occurred in the intermediate stage of bone cancer pain. The content of T lymphocytes and its subgroups, and the function of T lymphocyte proliferation are weakened to some extent in the bone cancer pain rat model.