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Objective:To observe the clinical efficacy of combining repeated transcranial magnetic stimulation (rTMS) with radiofrequency ablation (RF) of dorsal root ganglia in treating herpes zoster infection and neuralgia.Methods:Eighty-four individuals with a herpes zoster infection who had suffered from neuralgia for no more than 7 days were divided randomly into a control group, an rTMS group, an RF group, and an observation group, each of 21. All were treated with gabapentin, valciclovir and mecobalamin. The rTMS group received rTMS treatment, 5 days per week, for 2 consecutive weeks. The RF group received RF treatment of the dorsal root ganglia on the 15th day after enrollment, while the observation group received only the medication. Before the experiment as well as after 3, 7, 16, 30 and 60 days, all of the subjects self-assessed their discomfort using a pain visual analog scale (VAS). The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Quality of Life Assessment Scale (QOL-SF36), and Pittsburgh Sleep Quality Index (PSQI) were also administered.Results:The average VAS, HAMA, HAMD, QOL-SF36, and PSQI scores of the observation group improved continuously and significantly during and after the treatment. Beyond 16 days all of those results were significantly better than the control group′s averages, and the observation group′s average VAS, HAMA and HAMD results were also significantly better than those of the rTMS group. The observation group′s average VAS, HAMA, HAMD and PSQI scores had improved significantly more than the RF group′s averages beyond 30 days.Conclusion:Combining rTMS and dorsal root ganglion RF can effectively alleviate the early pain symptoms of herpes zoster infection and neuralgia, relieve anxiety and depression, and significantly improve sleep and life quality. Such therapy is worthy of clinical promotion and application.
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Objective:To investigate the effect of chronic compression of the dorsal root ganglion (CCD) on the Wnt/β-catenin signaling pathways in the spinal dorsal horns of rats.Methods:Forty-two adult male Sprague-Dawley rats were randomly divided into a sham group ( n=9) and a CCD group ( n=33). The CCD group was subdivided into a 1d group ( n=6), a 3d group ( n=6), a 7d group ( n=9), a 14d group ( n=6), and a 28d group ( n=6) based on the post-operative time of the experiments. Before the operation for CCD and 1, 3, 5, 7, 14, 21 and 28 days afterward the mechanical withdrawal threshold was detected for all rats. Western blotting was conducted to detect the expression of active β-catenin and glial fibrillary acidic protein (GFAP) in the dorsal horn of the spinal cord 1, 3, 7, 14 and 28 days after the surgery. Seven days after the operation immunofluorescence was employed to detect the nuclear translocation of active β-catenin and the activation of astrocytes in the dorsal horn of the spinal cord. Results:The average mechanical withdrawal thresholds of the CCD groups were significantly lower than that of the sham group at each time point. The western blotting showed that the expression of active β-catenin in the CCD groups was significantly greater than in the sham group at each time point. Seven days after compression the expression of GFAP in the rats′ dorsal horns was significantly higher than in the sham group. Immunofluorescence indicated nuclear translocation of active β-catenin and the activation of astrocytes in the dorsal horn.Conclusion:The Wnt/β-catenin signaling pathways are significantly activated in the dorsal horn of the spinal cord after CCD, at least in rats. It may play an important role in the development of neuropathic pain.
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BACKGROUND: Chronic nerve compression leads to muscle atrophy and fibrosis. Previous studies mainly focus on its pathogenesis. However, little is known about the dorsal root ganglia(DRG) responses to chronic nerve compression injury. OBJECTIVE: To investigate the effect of chronic sciatic nerve compression on fibrosis of the DRG. METHODS: Animal models of chronic sciatic nerve compression were made in rats according to the method described by Mackinnon. L4-6 ipsilateral and contralateral DRG were harvested 3 weeks post injury. Real-time RT-PCR, immunofluorescence and western blot were performed to determine the expression levels of transforming growth factor-β, connective tissue growth factor, and collagen type I in ipsilateral and contralateral DRG. RESULTS AND CONCLUSION: Three weeks after injury, the m RNA and protein expression of transforming growth factor-β, connective tissue growth factor and collagen type I were increased significantly in the ipsilateral DRG as compared with the contralateral DRG(P < 0.05). Transforming growth factor-β and connective tissue growth factor mainly expressed in DRG neurons and axons, while collagen type I formed a net structure that surrounded DRG neurons and axons. These findings indicate that chronic sciatic nerve compression can induce fibrotic changes in the DRG that appears to be associated with an increase in transforming growth factor-β and connective tissue growth factor expression in DRG neurons.
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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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Animals , Rats , Acupuncture Points , Bone Neoplasms , Cancer Pain , Therapeutics , Drug Tolerance , Electroacupuncture , Ganglia, Spinal , Metabolism , Histone Deacetylases , Metabolism , Morphine , Random Allocation , Rats, Sprague-Dawley , Receptors, Opioid, mu , MetabolismABSTRACT
Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of miRNA-325-5p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of miRNA-325-5p in a rat model of chronic visceral pain. This model was induced by neonatal colonic inflammation (NCI). In adulthood, NCI led to a significant reduction in the expression of miRNA-325-5p in colon-related dorsal root ganglia (DRGs), starting to decrease at the age of 4 weeks and being maintained to 8 weeks. Intrathecal administration of miRNA-325-5p agomir significantly enhanced the colorectal distention (CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2 (C-C motif chemokine ligand 2) in colon-related DRGs at the mRNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantly altered in NCI rats. CCL2 was co-expressed in NeuN-positive DRG neurons but not in glutamine synthetase-positive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding- and calcitonin gene-related peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in miR-325-5p-positive DRG neurons. Intrathecal injection of miRNA-325-5p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose- and time-dependent manner. These data suggest that NCI suppresses miRNA-325-5p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats.
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Objective To observe the clinical effect of combining extracorporeal shock waves with pulsed radiofrequency irradiation of the dorsal root ganglia in the treatment of spinal cord-derived abdominal pain. Methods A total of 88 patients were randomly divided into a control group, a shock wave group, a pulsed irradiation group and a combination group, each of 22. All of the patients were given etocoxib and pregabalin medication for 3 weeks. In ad-dition to the drugs, the shock wave group received extracorporeal shock wave therapy, and the irradiation group re-ceived pulsed radio frequency irradiation of the dorsal root ganglia. The combination group received both. A visual an-alogue scale was used to assess perceived pain. The quality of life short form 36 ( QOL-SF36) , Hamilton anxiety scale and Hamilton depression scale were administered to all 4 groups before the treatments and after 1, 4 and 12 weeks of the treatments. The development of diseases, gastrointestinal function, medical treatment and medical expenses of the 4 groups were observed for two years after the treatments. Results After 4 weeks of treatment, the average scores of all four groups in all of the evaluations had improved significantly compared with before the treatment. In combination group′s average results were significantly better than those of the other 3 groups from 4 weeks until 12 weeks after the treatment. During the subsequent two years that group′s gastrointestinal symptoms, hospital visits and medical expen-ses were all significantly lower, on average, than those of the other groups. Conclusion Extracorporeal shock waves combined with pulsed radio frequency irradiation of the dorsal root ganglia has significant clinical efficacy for alleviating spinal cord-derived abdominal pain. It can significantly reduce medical costs and is worthy of clinical pro-motion.
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OBJECTIVE@#To investigate the role of zinc-fingers and homeoboxes 2 (ZHX2) in regulating μ-opioid receptor expression in the dorsal root ganglion (DRG) in mice with peripheral nerve injury-induced pain hypersensitivity.@*METHODS@#Forty-eight male adult C57BL6J mice were randomized into 4 groups and subjected to chronic constriction injury (CCI) of the sciatic nerve or sham operation followed by microinjection of a specific small interfering RNA (siRNA) of ZHX2 or a negative control siRNA sequence (siNC) into the DRG. Seven days later, the mice were examined for changes in the hind paw withdrawal frequency (PWF), after which the DRG tissue was collected for detecting the expressions of μ-opioid receptor at the mRNA and protein levels using RT-qPCR and Western blotting. In another experiment, the DRG tissues were collected from 6 mice (21-day-old) for primary culture of the DRG neurons, which were transfected with ZHX2 siRNA or the siNC to observe the changes in the expressions of ZHX2 and μ-pioid receptor.@*RESULTS@#Microinjection of ZHX2 siRNA into the ipsilateral L3 and L4 DRGs significantly reversed CCI-induced μ-pioid receptor downregulation in the injured DRG and alleviated CCI-induced mechanical allodynia in the mice. In the cell experiment, ZHX2 knockdown obviously upregulated the mRNA and protein expressions of opioid receptor in the primary cultured DRG neurons.@*CONCLUSIONS@#ZHX2 knockdown in the DRG reverses CCI-induced down-regulation of μ opioid receptor to alleviate periphery nerve injury-induced pain hypersensitivity in mice.
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Animals , Male , Mice , Ganglia, Spinal , Homeodomain Proteins , Hyperalgesia , Neuralgia , Rats, Sprague-Dawley , Receptors, Opioid, muABSTRACT
Aim To investigate whether osthole can alleviate neuropathic pain induced by HIV gpl20 and its mechanism. Methods The paw withdrawal threshold and the paw withdrawal latency were observed to assess pain behaviors in four groups of the rats, including sham group, sham combined with osthole treatment group, gpl20 treatment group, and gpl20 combined with osthole treatment group. The protein expression levels of the P2X3 receptor, tumor necrosis factor-a receptor (TNF-aR), ERK, p-ERK in the L4-L6 dorsal root ganglia (DRG) were measured by Western blot. The mRNA expression level of P2X3 receptor was assessed by real-time quantitative polymerase chain reaction ( qPCR). The whole path clamp recording was used to measure HEK293 cell current activated by ATP. Results Osthole attenuated the mechanical and thermal hyperalgesia in gpl20 treated rats and down-regulated P2X3 receptor mRNA and protein expression in L4-L6 DRGs of gpl20 treated rats. Additionally, osthole simultaneously decreased the expression of TNF-ctR protein in L4-L6 DRGs and inhibited the phosphorylated ERK1/2 protein expression. Moreover, osthole reduced ATP activated current of HEK293 cells transfected with hP2X3R. Conclusion Osthole decreases the mechanical and thermal hyperalgesia induced by gpl20 through inhibiting P2X3R in DRG.
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Aim To investigate the effects of morphine preconditioning (MPC) on transient receptor potential vanilloid 1 (TRPV1) channel current in rat dorsal root ganglia (DRG) neurons and the phosphorylation (p) of TRPV1 and extracellular regulated protein kinases (ERK) in PC12 cells that sensitized by nerve growth factor (NGF). Methods DRG neurons isolated from T2-T8 segments of 10 days old SD rat or pheochromo-cytoma (PC12) cells were seeded into 24-well plates or 6-well plates, respectively, and randomly divided into 5 groups:control group (group C), NGF sensiti-zation group (group NGF), and morphine precondi-tioning groups (group MPC 0.3, group MPC 1.0 and group MPC 3.0). DRG neurons were identified by im-munofluorescent method with neuronal specific enolase (NSE). Cells were treated by morphine, NGF and capsaicin to simulate the effects of MPC on DRG neu-rons in T2-T8 segments during myocardial ischemia reperfusion injury (IRI). Afterwards, the inward cur-rent of DRG neurons induced by capsaicin in all groups were detected by whole cell recording; the expression and phosphorylation of TRPV 1 and ERK in PC12 cells were detected by Western blot. Results DRG neu-rons survived and grew nicely,and the staining of neu-ronal specific markers,NSE,was positive. In compar-ison with group C, the inward current of group NGF was enhanced (P <0.05), while MPC inhibited the enhancement (P <0.05). The relative expression of TRPV1,p-TRPV1 and p-ERK in group NGF was up-regulated when compared with group C (P <0.05).Moreover, the up-regulation was also suppressed by MPC (P <0.05). Conclusions MPC inhibits TR-PV1 channel current sensitized by NGF in neurocytes, and the mechanism might be associated with the down-regulation of TRPV1 p-TRPV1 and p-ERK expression.
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Objective To observe the clinical effect of pulsed radiofrequency electrotherapy combined with acupuncture or electroacupuncture in treating neuralgia after herpes zoster infection.Methods Eighty-eight patients were divided into a control group,an electroacupuncture group,a pulsed electrotherapy group and a combined group using a random number table.The 4 groups were routinely given gabapentin and tramadol,while the electroacupuncture group was additionally treated with electroacupuncture,the pulsed electrotherapy group received radiofrequency irradiation of the dorsal root ganglion,and the combined group was given CT-guided pulsed radiofrequency electrotherapy combined with electroacupuncture or acupuncture.Before the treatment and 15 days and 1 month afterward,everyone was evaluated using a visual analogue scale (VAS) for pain intensity,the Hamilton anxiety (HAMA) and depression (HAMD) scales and the short form 36 (QOL-SF36) quality of life assessment.The area of painful skin was also measured.Results There were no significant differences among the 4 groups at the outset in any of the measurements.Significant improvement was observed in all of the measurements 15 and 30 days after the treatment except in the control group.The combined group was by then significantly better than the other 3 groups.Their dosage of gabapentin and tramadol had decreased significantly compared with the other groups after 3 months of treatment.Conclusion CT-guided pulsed radiofrequency electrotherapy combined with acupuncture or electroacupuncture is safe and effective for treating post-herpes neuralgia.It is worthy of clinical application and promotion.
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Objective To evaluate the role of C-X-C chemokine receptor type 4 ( CXCR4) in the dorsal root ganglia ( DRG) in incisional pain in rats. Methods Thirty-two male Sprague-Dawley rats, aged 7-10 weeks, weighing 250-300 g, in which intrathecal catheters were successfully implanted, were divided into 4 groups (n＝8 each) using a random number table method: sham operation group (group S), CXCR4 antagonist AMD3100 plus sham operation group (group A+S), incisional pain group (group I) and CXCR4 antagonist AMD3100 plus incisional pain group (group A+I). Rats were anesthetized with sevoflu-rane. AMD3100 20 μg (in 10 μl of normal saline) was intrathecally injected, and no incision was made 30 min later in group A+S. A 1-cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the left hindpaw in group I. AMD3100 20 μg (in 10 μl of normal saline) was intrathecally injected, and 30 min later the model of incisional pain was established in group A+I. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured at 24 h before surgery and 2, 4, 8, 16 and 24 h after surgery. The rats were sacrificed after the last measurement of pain threshold and the DRGs of the lumbar segment (L4-6) were removed for detecting the expression of CXCR4, phosphorylated extracellular regulated protein kinase ( p-ERK) and total ERK ( t-ERK) by Western blot. Results Compared with group S, MWT was significantly decreased and TWL was shortened at T1-5in group I and group A+I, and the expression of CXCR4 and p-ERK in DRGs was significantly up-regulated (P＜0. 05), and no significant change was found in the expression of t-ERK in group I, no significant change was found in the expression of CXCR4, p-ERK and t-ERK in group A+I, and no significant change was found in the parameters mentioned above in group A+S (P＞0. 05). Compared with group I, MWT was significantly increased and TWL was prolonged at T1-5, the expression of CXCR4 and p-ERK in DRGs was down-regulated (P＜0. 05), and no significant change was found in the expression of t-ERK in group A+I (P＞0. 05). Conclusion CXCR4 in DRGs is involved in incisional pain, and the mechanism may be re-lated to activating ERK1∕2 signaling pathway in rats.
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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 (n＝5 in the sham-HP group and n＝6 in the HP group for the test of MHTs, n＝8 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 (n＝16 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, 0.5－1.5 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 4－L 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 4－L 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.
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Objective To compare the curative effect of treating postherpetic neuralgia (PHN) by dorsal root ganglia pulsed radiofrequency combined ozone and simple dorsal root ganglia pulsed radiofrequency.Methods 68 cases of chest and back PHN patients in accordance with incorporation standard were randomly divided into two groups:control group (n =34) received dorsal root ganglia pulsed radiofrequency while experimental group (n =34) received dorsal root ganglia pulsed radiofrequency combined ozone.The visnal analogue scale (VAS) of two groups before treatment,and 1,3,7 days,1,3 and 6 months after treatment was observed and compared;the clinical treatment effect was evaluated.Results VAS of two groups after treatment all declined obviously compared with that before treatment (P =0.000).Compared with control group,the VAS of experimental group 1 and 3 days after treatment was not significantly different (P＞ 0.05).However,the VAS 7 days,1 and 3 months after treatment declined obviously (P ＜ 0.05).The obvious effect rate of experimental group was higher than control group,so the difference was statistically different (P ＜ 0.05).Patients in both of the groups obtained satisfying curative effect,among which the effective rates of control group and experimental group were 85.29％ and 91.18％ separately.The difference was not statistically different (P ＜ 0.05).But the obvious effect rate of experimental group (70.59％) was higher than control group (38.24％),and the difference was statistically different (P ＜ 0.05).Conclusion Both dorsal root ganglia pulsed radiofrequency combined ozone and simple dorsal root ganglia pulsed radiofrequency generate effect in treating postherpetic neuralgia.But the curative effect of dorsal root ganglia pulsed radiofrequency combined ozone is superior to simple dorsal root ganglia pulsed radiofrequency within medium and long term;therefore,it is a safe and effective treatment.
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Objective To compare the curative effect of treating postherpetic neuralgia (PHN) by dorsal root ganglia pulsed radiofrequency combined ozone and simple dorsal root ganglia pulsed radiofrequency.Methods 68 cases of chest and back PHN patients in accordance with incorporation standard were randomly divided into two groups:control group (n =34) received dorsal root ganglia pulsed radiofrequency while experimental group (n =34) received dorsal root ganglia pulsed radiofrequency combined ozone.The visnal analogue scale (VAS) of two groups before treatment,and 1,3,7 days,1,3 and 6 months after treatment was observed and compared;the clinical treatment effect was evaluated.Results VAS of two groups after treatment all declined obviously compared with that before treatment (P =0.000).Compared with control group,the VAS of experimental group 1 and 3 days after treatment was not significantly different (P＞ 0.05).However,the VAS 7 days,1 and 3 months after treatment declined obviously (P ＜ 0.05).The obvious effect rate of experimental group was higher than control group,so the difference was statistically different (P ＜ 0.05).Patients in both of the groups obtained satisfying curative effect,among which the effective rates of control group and experimental group were 85.29％ and 91.18％ separately.The difference was not statistically different (P ＜ 0.05).But the obvious effect rate of experimental group (70.59％) was higher than control group (38.24％),and the difference was statistically different (P ＜ 0.05).Conclusion Both dorsal root ganglia pulsed radiofrequency combined ozone and simple dorsal root ganglia pulsed radiofrequency generate effect in treating postherpetic neuralgia.But the curative effect of dorsal root ganglia pulsed radiofrequency combined ozone is superior to simple dorsal root ganglia pulsed radiofrequency within medium and long term;therefore,it is a safe and effective treatment.
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Objective To explore the analgesic effect of intra-articular botulinum neurotoxin type A (BoNTA) injection in rats with adjuvant-arthritis pain,to quantify the expression of calcitonin gene-related peptide (CGRP) in the dorsal root ganglia (DRG) associated with arthritis pain,and to investigate the retrograde axonal transport of BoNT-A into the DRG after peripheral injection.Methods Ninety Sprague-Dawley rats were randomly divided into groups A,B,C,D and E,each of 18.A murine model of adjuvant-arthritis pain was established by injecting 50 μL of complete Freund's adjuvant into the left ankle in all the mice except those in group A.The control group A was treated with intra-articular injection of 50 μL of saline solution.Three weeks later,groups A and B were treated with a 20 μL intra-articular saline injection,while groups C,D and E received an intra-articular injection of BoNT-A at 1 U/20 μL,3 U/20 μL or 10 U/20 μL respectively.Pain threshold and muscle strength were graded before and 1,5,15 and 21 days after the modelling,as well as at 1,3,5 and 14 days after the BoNT-A treatments.Protein expression and the CGRP-positive cell number were observed,as well as any BoNT-A-cleaved synaptosomal-associated 25 kDa protein (cl-SNAP-25) in the DRG using Western blotting and immunofluorescence.Results Compared with group A,there was a significant decrease in the average mechanical withdrawal threshold and muscle strength and a significant increase in the protein expression and the CGRP-positive cell number in the other 4 groups.Compared with group B,the mechanical withdrawal threshold had increased significantly more in groups D and E at 5 days after the BoNT-A injection and in group C at 14 days after the treatment.Compared with group B,the protein expression and the number of CGRP-positive cells were significantly lower in groups D and E at 3 days after the BoNT-A injection.The decrease in group C was significant after 14 days.No significant differences were found between groups D and E in any measurement at any time point.There was no significant difference among groups B,C and D in terms of muscle strength.Five days after the BoNT-A injection,significantly decreased muscle strength was observed in group E.In addition,BoNT-A cleaved-SNAP-25 was detected in the DRG.Conclusion BoNT-A can reduce arthritis pain through inhibiting the expression of CGRP in the DRG.Its analgesic effect has a dose response.A peripheral injection of BoNT-A can arrive at the DRG through retrograde axonal transport.
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Objective:To study the expression of adult and neonatal Nav1.5 isoforms in the dorsal root ganglia (DRG) neurons of rats with spared nerve injury (SNI) . Methods:The expression of adult and neonatal Nav1.5 isoforms in the DRG neurons of rats with SNI was detected by RT-PCR, DNA sequencing, restriction enzyme digestion, immunohistochemistry and immunofluo-rescence methods. The expression of PKC-γwas detected by Western blot. Results:Both adult and neonatal Nav1.5 isoforms were expressed in the DRG neurons, but their expression ratio was approximately 2.5∶1. In SNI rat models, the expression of both adult and neonatal Nav1.5 isoforms decreased by approximately a half in both mRNA and protein levels. In contrast, the expression of PKC-γincreased by approximately one-fold. Conclusions:Both adult and neonatal Nav1.5 isoforms expressed in the DRG neurons of rat,but their expression levels decrease in pain models. The up-regulation of PKC-γmay directly or indirectly down-regulate the expression of Nav1.5 isoforms in SNI rat models,which may further involve in the pathological process of neuropathic pain.
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<p><b>OBJECTIVE</b>To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats.</p><p><b>METHODS</b>Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method.</p><p><b>RESULTS</b>Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05).</p><p><b>CONCLUSION</b>H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.</p>
Subject(s)
Animals , Female , Agaricales , Chemistry , Axons , Pathology , Ganglia, Spinal , Metabolism , Glucans , MAP Kinase Signaling System , Nerve Crush , Nerve Regeneration , Physiology , Peripheral Nerves , Physiology , Peroneal Nerve , Physiology , Protein Biosynthesis , Proto-Oncogene Proteins c-akt , Metabolism , Proto-Oncogene Proteins c-fos , Genetics , Metabolism , Proto-Oncogene Proteins c-jun , Genetics , Metabolism , Rats, Sprague-DawleyABSTRACT
[ ABSTRACT] AIM:To observe the change of skin histology in diabetic rats and to investigate the possible me-chanism of c-Jun N-terminal kinase (JNK) protein in the dorsal root ganglion (DRG) during the process.METHODS:Diabetic animal model was established in the male SD rats by intraperitoneal injection of streptozotocin.Plantar skin speci-mens of the rats were collected from control group, DM 2-week group (DM2), DM 4-week group (DM4), and DM 8-week group ( DM8) .Immunohistochemical staining and HE staining were used to observe the change of PGP 9.5 immunoreactive nerve terminals and the structures of the skin tissues.The protein expression of PGP 9.5 in the plantar skin tissues, and JNK and p-JNK protein in the DRG within lumbar 5, 6 (L5, 6), and sacral 1 (S1) spinal cord segments were detected by Western blotting.RESULTS:PGP 9.5 immunoreactive nerve terminals of the plantar skin of the rats mainly distributed in the basal layer of the epidermis and papillary dermis.Compared with control group, PGP 9.5 positive nerve terminals in DM4 group showed reduced density and sparse distribution.PGP 9.5 positive nerve terminals in DM8 group showed signifi-cantly reduced distribution, thinner nerve diameter, shorter length and distorted shape.Histological changes of the thinner epidermal tissue, reduced epidermal cell layers, uneven cell distribution and arrangement in DM4 group, and significantly reduced epidermal cell layers, swollen and blurred cells, increasing cell gap, lack of stratified epidermis arrangement for part of epidermis, atropal and degenerated dermal collagen fiber, significantly decreased subcutaneous fat in DM8 group were observed.The results of Western blotting showed that the protein expression of PGP 9.5 in the plantar skin tissue of DM rats was progressively decreased along with the disease, while the protein level of p-JNK in L5, 6-DRG or S1-DRG showed a gradual increasing trend.PGP 9.5 immunoreactive positive nerve terminal density of plantar skin in DM rats had a negative correlation with the protein level of p-JNK in L5, 6-DRG and S1-DRG (P<0.01), but showed a significant positive correlation with the plantar skin thickness (P<0.01).CONCLUSION:The protein level of p-JNK within L5, 6-DRG or S1-DRG in DM rats shows a progressive enhancement.At the same time, there is a significant change in the skin tissue density and structure.The changes of skin tissue and nerve morphology in DM rat may be related to the activation of JNK/SAPK pathway in L5, 6-DRG or S1-DRG cells.Blocking or inhibiting JNK/SAPK pathway may delay the diabetic pe-ripheral neuropathy and reduce the risk of skin lesions.
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Objective To observe the biocompatibility of bacterial cellulose and Schwann cells during in vitro co-culture, so as to lay a foundation for preparing tissue-engineered nerve with bacterial cellulose. Methods The bacterial cellulose was co-cultured with the dorsal root ganglion. The morphology, proliferation, and migration of the Schwann cells were examined by scanning electron microscope and optical microscope at day 1, 2, and 5, and the protein expression of S-100 was detected by immunocytochemical method. Schwann cells were also cultivated in the leach liquor of bacterial cellulose, and then optical microscope and immunocytochemical were used to observe the morphology and S-100 protein expression after 24, 48 and 72 hours; MTT and flow cytometry were used to evaluate the biocompatibility of the bacterial cellulose and Schwann cells. Results Schwann cells could grow and migrate on the surface of bacterial cellulose's membrane. The Schwann cell growth, proliferation and S-100 expression were not significantly affected by the leach liquor of bacterial cellulose as compared with the control group. Conclusion Schwann cells can grow well on the surface of the bacterial cellulose membrane and in its leach liquor, suggesting good biocompatibility with bacterial cellulose in vitro.
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Objective To study the effect of APETx2 on the expression of ASIC3 APETx2 in a rat model of acute gastric mucosal lesion(AGML). Methods Twenty-four Wistar rats were randomly assigned to three groups in equal number : normal control group, water immersion restraint stress (WIRS) group, APETx2 treatment group. AGML was induced by WIRS for 6 hours, and APETx2 (25 μg/kg) was injected intraperitoneally before the onset of stress. Intragastric pH and gastric histopathological changes were measured and the expression of ASIC3 mRNA in DRG neurons projecting to rat stomach was examined by real-time PCR. Immunohistochemistry was performed to detect the localization of ASIC3. Results Compared with the normal control group, the WIRS group showed obvious gastric injury with lower values of intragastric pH and extensive expression of ASIC3 in the DRG neurons (P < 0.05). The treatment with APETx2 before the onset of WIRS significantly alleviated the gastric mucosal injury, decreased gastric acidity and reduced ASIC3 expression in DRG neurons (P < 0.05). Conclusions ASIC3 expression in DRG neurons projecting to rat stomach is strongly associated with gastric mucosal lesion and acidosis in the WIRS model. APETx2 can improve gastric acidosis and prevent the occurrence of these lesions.