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1.
Article in Chinese | WPRIM | ID: wpr-1019634

ABSTRACT

Objective:To explore the feature of FOS expression in oxytocin-and vasopressin-positive neurons in the hypothalamic paraventricular nucleus(PVN)under different status of diabetes mellitus(DM).Methods:Intraperito-neal injection of vehicle or STZ in mice was conducted to establish control or diabetes model.Mechanical sensitivity was evaluated by von Frey filament tests to distinguish diabetic neuropathic pain(DNP)from without-pain group(DWP).The expression of FOS,oxytocin(OXT)-and vasopressin(VP)-positive neurons,as well as their double labeling was detected by immunohistochemical and immunofluorescent staining.Cell counting and comparison were made in groups.Results:FOS expression was easily detected in the PVN in the three groups(Control group,DNP group and DWP group)at 7 days,while that in DWP and DNP groups at 28 days was hardly detectable,with the number being signifi-cantly different from the 7 days group(P<0.05 or 0.001).Likewise,compared with the control group,immunofluo-rescent signals for VP and OXT staining in the DNP and DWP groups also showed a trend of weakening as the modeling time increased(P<0.05).The cell counting after double staining for VP or OXT with FOS showed that,in the DWP group at 7 days,the number of VP and FOS double-labeled neurons was 74.33±22.10,accounting for(56.64± 7.52)%of VP-positive cells,whereas the double labeling rate for OXT and FOS was only(10.44±3.14)%.In the DNP group at 7 days,the number of OXT and FOS double-labeled neurons was 51.00±31.80,accounting for(18.50 ±9.51)%of OXT-positive neurons,whereas the double labeling rate for VP and FOS was only(9.34±3.27)%.In contrast to these changes in 7 days group,the expression of FOS decreased sharply in the group of 28 days,thereby al-most no double-labeled neurons.Conclusion:The plasticity changes of oxytocin-and vasopressin-positive neurons in the PVN are different depending on the status of pain and non-pain,and the stage of disease progression.Understanding the changes is of great significance for unravelling the neural mechanism of diabetes and its complications.

2.
Article in Chinese | WPRIM | ID: wpr-997655

ABSTRACT

ObjectiveTo investigate the mechanism of Yiqi Huoxue Tongluo prescription (YHTP) in the treatment of diabetic neuropathic pain (DNP). MethodNinety SPF-grade SD male rats were randomized into blank, model, low- (2.25 g·kg-1), medium- (4.5 g·kg-1), and high-dose (9 g·kg-1) YHTP, and mecobalamin (0.175 mg·kg-1) groups. Except those in the blank group, the rats in the remaining 5 groups were fed with a high-fat and high-glucose diet and subjected to intraperitoneal injection of low-dose (35 mg·kg-1) streptozotocin (STZ) to establish the model of DNP. The sciatic nerve conduction velocity in DNP rats was measured by the neurophysiological method, and the levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to measure the mRNA levels of glial fibrillary acidic protein (GFAP) and extracellular signal-regulated kinase (ERK) in the spinal cord. Western blot was employed to measure the protein levels of GFAP and phosphorylated ERK (p-ERK), and immunofluorescence staining to measure the fluorescence intensity of GFAP and p-ERK in the spinal cord. In the cell experiments, 100 mmol·L-1 high glucose was used to induce the activation of astrocytes (CTX-TNA2) for the modeling of nerve cell injury. The cells were randomized into the normal, model, drug-containing serum (10% YQHT), inhibitor [10 mol·L-1 corynoxeine (COR)], drug-containing serum + inhibitor (10% YHTP + 10 mol·L-1 COR) groups. The levels of pro-inflammatory factors (TNF-α and IL-1β) and the anti-inflammatory factor IL-10 in CTX-TNA2 cells were determined by ELISA, and the protein levels of GFAP and p-ERK in CTX-TNA2 cells by Western blot. ResultThe animal experiments showed that compared with the blank group, the model group presented reduced mechanical withdrawal threshold (MWT), thermal work limit (TWL), and nerve conduction velocity, elevated levels of fasting blood glucose, IL-1β, TNF-α, and IL-6, and up-regulated protein levels of GFAP and p-ERK, and mRNA levels of ERK1, ERK2, GFAP (P<0.01). Compared with model group, YHTP increased the MWT, TWL, and sciatic nerve conduction velocity (P<0.01), lowered the levels of IL-1β, TNF-α, and IL-6 (P<0.01), and down-regulated the protein levels of GFAP and p-ERK, and mRNA levels of ERK1, ERK2, GFAP in the spinal cord (P<0.05, P<0.01). The cell experiments showed that compared with the blank group, the model group had decreased survival rate, elevated levels of pro-inflammatory factors, and up-regulated protein levels of ERK and GFAP (P<0.01). Compared with the model group, the YHTP-containing serum lowered the levels of IL-1β and TNF-α (P<0.05, P<0.01), elevated the level of IL-10 (P<0.01), and down-regulated the protein levels of ERK and GFAP (P<0.01). ConclusionYHTP may inhibit the activation of astrocytes by inhibiting the ERK signaling pathway to reduce inflammation and thus relieve DNP.

3.
Neuroscience Bulletin ; (6): 745-758, 2023.
Article in English | WPRIM | ID: wpr-982441

ABSTRACT

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.


Subject(s)
Mice , Animals , Diabetes Mellitus, Experimental/metabolism , Axons/physiology , Diabetic Neuropathies , Sensory Receptor Cells/metabolism , Neuralgia/metabolism
4.
Article in Chinese | WPRIM | ID: wpr-940753

ABSTRACT

Diabetic neuropathic pain (DNP) is one of the common complications of diabetic peripheral neuropathy, which is difficult to be cured. The clinical manifestations of DNP include reduced pain threshold, neuropathic pain in extremities, and abnormal pain. Studies have demonstrated that nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), nuclear factor erythroid 2-related factor 2 (Nrf2), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways are involved in the treatment of DNP by inhibiting the activation and release of inflammatory cytokines [e.g., tumor necrosis factor-alpha (TNF-α) and interleukin (IL)], regulating inflammation-mediating factors [e.g., reactive oxygen (ROS), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and NF-κB inhibitor (IκB)], suppressing neurogenic inflammation, destroying the persistent damage of peripheral nerves, and repairing damaged peripheral nerves. The literature of modern medical research has demonstrated that the treatment of DNP with Chinese herbal medicines is associated with the signaling pathways above. They can treat DNP by regulating the expression of key proteins in the signaling pathways to control neurogenic inflammation and repair diabetic peripheral neuropathic damage. By summarizing the available studies, this review aims to provide a reference for the in-depth research on Chinese herbal medicines in the treatment of DNP and give new insights into the protection of diabetic peripheral nerves and the treatment of DNP with Chinese herbal medicines.

5.
Zhongguo zhenjiu ; (12): 173-178, 2022.
Article in Chinese | WPRIM | ID: wpr-927354

ABSTRACT

OBJECTIVE@#To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP.@*METHODS@#PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection.@*RESULTS@#PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection (P<0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection (P<0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection (P<0.05, P<0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection (P<0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection (P<0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection (P<0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased (P<0.01).@*CONCLUSION@#The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.


Subject(s)
Animals , Male , Rats , Diabetes Mellitus, Experimental/therapy , Electroacupuncture , Neuralgia/therapy , Rats, Sprague-Dawley , Spinal Cord , Spinal Cord Dorsal Horn
6.
Zhongguo Zhong Yao Za Zhi ; (24): 2533-2540, 2022.
Article in Chinese | WPRIM | ID: wpr-928133

ABSTRACT

Neuropathic pain is one of the common complications of diabetes. Tetrahydropalmatine(THP) is a main active component of Corydalis Rhizoma with excellent anti-inflammatory and pain-alleviating properties. This study aims to investigate the therapeutic effect of THP on diabetic neuropathic pain(DNP) and the underlying mechanism. High-fat and high-sugar diet(4 weeks) and streptozotocin(STZ, 35 mg·kg~(-1), single intraperitoneal injection) were employed to induce type-2 DNP in rats. Moreover, lipopolysaccharide(LPS) was used to induce the activation of BV2 microglia in vitro to establish an inflammatory cellular model. Fasting blood glucose(FBG) was measured by a blood glucose meter. Mechanical withdrawal threshold(MWT) was assessed with von Frey filaments, and thermal withdrawal latency(TWL) with hot plate apparatus. The protein expression levels of OX42, inducible nitric oxide synthase(iNOS), CD206, p38, and p-p38 were determined by Western blot, the fluorescence expression levels of OX42 and p-p38 in the dorsal horn of the rat spinal cord by immunofluorescence, the mRNA content of p38 and OX42 in rat spinal cord tissue by qRT-PCR, and levels of nitric oxide(NO), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and serum fasting insulin(FINS) by enzyme-linked immunosorbent assay(ELISA). RESULTS:: showed that the mo-del group demonstrated significant decrease in MWT and TWL, with pain symptoms. THP significantly improved the MWT and TWL of DNP rats, inhibited the activation of microglia and p38 MAPK signaling pathway in rat spinal cord, and ameliorated its inflammatory response. Meanwhile, THP promoted the change of LPS-induced BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed the activation of the p38 MAPK signaling pathway, decreased the expression levels of inflammatory factors NO, IL-1β, IL-6, and TNF-α, and increased the expression level of anti-inflammatory factor IL-10. The findings suggested that THP can significantly ameliorate the pain symptoms of DNP rats possibly by inhibiting the inflammatory response caused by M1 polarization of microglia via the p38 MAPK pathway.


Subject(s)
Animals , Rats , Berberine Alkaloids , Blood Glucose/metabolism , Diabetes Mellitus , Diabetic Neuropathies/genetics , Interleukin-10 , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Microglia , Neuralgia/metabolism , Rats, Sprague-Dawley , Signal Transduction , Spinal Cord/metabolism , Streptozocin/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
7.
Article in Chinese | WPRIM | ID: wpr-845213

ABSTRACT

Objective: To investigate analgesic effect of gabapentin(GBP)combined with agmatine(AGM)on diabetic neuropathic pain(DNP)model rats and explore possible mechanism. Methods: SPF SD male rats were injected intraperitoneally with STZ 65 mg/kg to create a neuropathic pain model of diabetic rats. The model rats were randomly divided into 5 groups(n=8): the model group, low-dose GBP group(30 mg/kg, ip), high-dose GBP group(100 mg/kg, ip), AGM group(80 mg/kg, ig)and the GBP-AGM combined group(GBP 30 mg/kg, ip+AGM 80 mg/kg, ig). In addition, a control group was set with 8 randomly selected normal rats. The control group and the model group were intragastrically and intraperitoneally administered an equal volume of physiological saline, respectively, while the test groups were administered drugs with the given dose in the indicated manner, all for continuous 14 days. The rat body mass, tail vein blood glucose, mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL) were measured on day 1 before STZ injection and every 7th day after STZ injection, and the plantar tenderness meter was used for the MWT and TWL measurement. The rats were sacrificed 24 h after the last administration, and the spinal cord tissues were harvested. Western blotting was used to detect the expression of p-ERK and c-Fos protein in spinal cord tissues. Results: Compared with the normal control group, the body mass was reduced, blood glucose increased, MWT decreased, and TWL shortened in the model group, all significantly(P0.05)in all of the drug-test groups, while the MWT was increased and the TWL was prolonged in the GBP 100 mg/kg group and the GBP-AGM combined group(both P<0.01). Western blotting results showed that the level of p-ERK and c-Fos protein in the spindal cord was significantly higher in the model group than in the control group(P<0.05). Further, the p-ERK and c-Fos protein level was significantly lower in the GBP+AGM combined group than in the model group(P<0.05)and there was no statistical difference between the GBP 100 mg/kg group and the GBP-AGM combination group. Conclusion: The combination of GBP 30 mg/kg with AGM 80 mg/kg could alleviate neuropathic pain in diabetic rats, which is similar to GBP 100mg/kg and the analgesic effect is likely related to the inhibition of ERK/c-Fos signaling pathway in the spina cord.

8.
Article in English | WPRIM | ID: wpr-781227

ABSTRACT

Neuropathic pain (NP) has become a serious global health issue and a huge clinical challenge without available effective treatment. P2 receptors family is involved in pain transmission and represents a promising target for pharmacological intervention. Traditional Chinese medicine (TCM) contains multiple components which are effective in targeting different pathological mechanisms involved in NP. Different from traditional analgesics, which target a single pathway, TCMs take the advantage of multiple components and multiple targets, and can significantly improve the efficacy of treatment and contribute to the prediction of the risks of NP. Compounds of TCM acting at nucleotide P2 receptors in neurons and glial cells could be considered as a potential research direction for moderating neuropathic pain. This review summarized the recently published data and highlighted several TCMs that relieved NP by acting at P2 receptors.

9.
Article in Chinese | WPRIM | ID: wpr-1034948

ABSTRACT

Objective To delineate the expressions of ubiquitin-specific proteinase 49 (USP49)and FK506 binding protein 51 (FKBP51) in the spinal dorsal horns and their roles in rats with diabetic neuropathic pain (DNP).Methods Male SD rats were fed with high glucose and high fat diet with an intraperitoneal injection of 1% streptozocin to establish DNP rat models.DNP rats were allocated into DNP group,control shRNA group (KC group) and knockdown USP49 group (KD group,n=10);saline,Ad-scrambled shRNA (3×108 PFU/mL) and Ad-USP49-shRNA (3×108 PFU/mL) were intrathecally injected into the rats of the three groups.Another 10 normal rats were chosen as control group (C group).Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured one d before model establishment,one and 7 d after model establishment,one,three and 7 d after intrathecal injection.The mRNA and protein expressions of USP49,FKBP51 and glucocorticoid receptor α (GRα)in dorsal horn neurons were detected by real time-PCR and Western blotting.Results (1) TWL showed no significant difference among the four groups one d before model establishment (P>0.05);three and 7 d after intrathecal injection,TWL in KD group was significantly prolonged as compared with that in the DNP group,and significantly shortened as compared with that in C group (P<0.05).(2) MWT showed no significant difference among the four groups one d before model establishment (P>0.05);three and 7 d after intrathecal injection,MWT in KD group was significantly higher as compared with that in the DNP group,and significantly lower as compared with that in C group (P<0.05).(3) As compared with DNP group,KD group had significantly decreased mRNA expressions of USP49 and FKBP51,and statistically increased mRNA GRα expression (P<0.05).(4) As compared with DNP group,KD group had significantly decreased protein expressions of USP49 and FKBP51,and statistically increased protein GRα expression (P<0.05).Conclusion Specific knockdown of USP49 expression is associated with improvement of heat hyperalgesia and mechanical hyperalgesia in DNP rats,which may be attributed to the de-ubiquitination ofFKBP51 by USP49.

10.
Article in Chinese | WPRIM | ID: wpr-710032

ABSTRACT

Objective To investigate the effect of systemic administration of gabapentin on the expression of Nrf2 in dorsal root ganglion neurons in a rat model of diabetic neuropathic pain (DNP). Methods 60 male SD rats weighing 200-220 g were randomly divided into 4 groups (n= 15 each): control group (group C), DNP group, saline group (SC + DNP group) and gabapentin group ( GBP + DNP group). Diabetes was induced with streptozocin (70 mg/ kg) subcutaneously. Paw withdrawal mechanical threshold ( PWMT) and paw withdrawal thermal latency (PWTL) were measured at 1d before and 3,7,10,14,21, and 28 d after streptozocin injection, and 21 and 28 d after administration of gabapentin (50 mg·kg-1 ·d-1 ,once) intraperitoneally. Saline and gabapentin (50 mg·kg-1 · d-1 ) were given intraperitoneally once a day for 7 d starting from 15 d after streptozocin injection in saline and gabapentin groups respectively. The expression of Nrf2 was determined at 21 d after streptozocin injection by immune-histochemistry and Western blot. Results Compared with group C, PWMT ( 3. 95 ± 0. 57) was significantly decreased, PWTL(6.3 ± 0.81) was significantly shorten, Nrf2 in expression was significantly decreased in DNP, SC+DNP and group (P<0.05). Compared with SC+DNP group, PWMT(8.2 ± 0.79) was significantly increased, PWTL(9.7 ± 1.13) was significantly prolonged, Nrf2 expression was significantly increased in GBP+DNP group (P<0.05). There was no significant difference in the parameters mentioned above between DNP and SC+DNP group (P>0.05). Conclusion Systemic administration of gabapentin attenuates diabetic neuropathic pain by enhancing the expression of Nrf2 in DRG neurons.

11.
Article in Chinese | WPRIM | ID: wpr-694932

ABSTRACT

Objective To observe the effect of miR-145 on pain threshold and explore the pos-sible underlying positive role of miR-145 in rats with diabetic neuropathic pain.Methods The total of 36 rats with diabetic neuropathic pain were randomly divided into three groups respectively with nor-mal control group (group N)(n=12 for each group):diabetic neuropathic pain(DNP)group (group D),DNP-NC group (group DN)and DNP-agomiR-145 group (group agomiR-145).The rats received agomiR-145 intrathecal injection in group agomiR-145 (10 μl,1×106TU/ml),or the negative control virus in group DN (10 μl,1×106TU/ml),or equal volume of normal saline in other two groups. Paw mechanical withdrawal threshold(MWT)and paw withdrawal latency(TWL)were measured on the day before intrathecal injection and day 1,days 3,7 and 14 after intrathecal injection.On the days 14 after pain-related behavioral test,the RNA expression of miR-145 in the dorsal root ganglion (DRG)was detected using reverse transcription-quantitative polymerase chain reaction(RT-PCR)as-say and the expression of Nav 1.8 in DRG were detected by fluorescent immunofluorescence.In addi-tion,a dual luciferase activity assay was used to testify the target genes of miR-145.Results MWT and TWL were decreased at 1 d before intrathecal injectionin groups D,DN and agomiR-145 than that in group N (P<0.05).The significant increase of MWT was observed in group agomiR-145 on day 3,7,14 than those in group D and group DN (P<0.05).TWL in group agomiR-145 was increased significantly on day 7 and day 14 compared with those in groups D and DN (P<0.05).Compared with group N,miR-145 expression level in DRG in groups D and DN were significantly lower (P<0.05).In addition,the protein expression of Nav1.8 was significantly increased in group D and DN compared with that in group N (P<0.05).Compared with groups D and DN,miR-145 expression was increased significantly and the expression of Nav1.8 in DRG was decreased significantly in group agomiR-145 (P<0.05).In addition,a dual luciferase reporter assay demonstrated that miR-145 can bind with the 3'-UTR region of Nav1.8 and regulate its expression.Conclusion Intrathecal agomiR-145 can effectively attenuate neuropathic pain of DNP rats,which may be related with down-regulation of Nav1.8 in DRG..

12.
Yao Xue Xue Bao ; (12): 355-361, 2017.
Article in Chinese | WPRIM | ID: wpr-779600

ABSTRACT

Diabetic neuropathic pain (DNP) is the most common chronic complication of diabetes mellitus, significantly affecting people's quality of life. Studies have indicated that ion channels play a very important role in the occurrence of DNP. This review provides a summary in the role of ion channels in diabetic neuropathic pain and treatment strategies for diabetic neuropathy targeting ion channels.

13.
Article in Chinese | WPRIM | ID: wpr-509927

ABSTRACT

Objective To investigate the effects of low frequency electroacupuncture on the P2X3 receptor expres-sion in dorsal root ganglion ( DRG) of rats with type II diabetic neuropathic pain. Methods Part 1:Fifty normal SD rats were randomly divided into normal group (8 rats) and model group (42 rats). The rat model of type II diabetic neuropathic pain was generated by high fat and high sugar diet with a single intraperitoneal injection of streptozotocin ( STZ, 35 mg/kg) . 2 Hz electroacupuncture was administered at ipsilateral acupoints Zusanli and Kunlun for consecutive 7 days. Insulin sensitivity index ( ISI) was measured at 0 w and 5 w, and fasting plasma glucose ( FPG) was measured at 0 w, 5 w, and 7 w. Paw withdrawal threshold (PWT) was measured by mechanical pain threshold, and P2X3 receptor was determined by immunofluorescence. Part 2:Twelve rats with diabetic neuropathic pain (DNP) were divided into EA + vehicle group (6 rats) and EA + αβ?meATP group (6 rats). Rats in the two groups received the same EA treatment as Part 1. Rats in the EA + αβ?meATP group were injected with P2X3 receptor agonistαβ?meATP (0. 6μmol/L, 100μL) into the ventral sur?face of each hind paw every time before EA treatment. Rats in the EA + vehicle group received the same dose of vehicle ( PBS buffer) as a control. Pain threshold of the rats were measured. Results ① Compared with the normal group, the ISI levels of the rats in DNP group was significantly decreased after 5 weeks of the high?fat high?sugar diet (P < 0. 01). Two weeks after STZ injection, the fasting plasma glucose levels in the rats receiving STZ were significantly elevated ( P <0. 01 ) . The type 2 diabetes model was established with a successful rate of 69. 04%. ②PWTs:The PWTs of rats in DNP group were reduced compared with rats in the normal group (P < 0. 01), indicating that the type 2 DNP model was suc?cessfully established. Compared with the PWTs of DNP?controlled rats, the 2 Hz electroacupuncture significantly increased bilateral PWT of rats subjected to DNP from day 3 after treatment (P < 0. 01). P2X3 receptor agonistαβ?meATP greatly reduced bilateral PWT of EA?treated DNP rats compared with that of the EA + vehicle group (P < 0. 01). ③The immu?nofluorescence essay showed that P2X3 receptor expression in bilateral L5 DRGs in the DNP group was significantly in?creased as compared with that in the normal group ( P < 0. 01 ) . The increases were inhibited by 2 Hz EA in L5 DRGs compared with the DNP group (P < 0. 01). Conclusions 2Hz electroacupuncture can effectively treat the type II diabet?ic neuropathic pain by decreasing the expression of L5 DRG P2X3 receptors in rats.

14.
Article in Chinese | WPRIM | ID: wpr-463179

ABSTRACT

Diabetic neuropathic pain(DNP)is one of the most common complications in clinical, which influenced patients’ daily functions greatly, without clear mechanisms and effective methods.P2X3 receptors play a pivotal role in the formation, transmission and conduction of pain under neuropathic pain models, associated with peripheral sensory nerve excitability enhancement.This paper focuses on the establishment of DNP models, and the effects of P2X3 receptors in diabetes mellitus.

15.
Experimental Neurobiology ; : 144-152, 2011.
Article in English | WPRIM | ID: wpr-7982

ABSTRACT

The anti-allodynic effect of NMDA receptor antagonist and acupuncture treatments were explored through spinal p35 regulation of diabetic neuropathic rat. We evaluated the change over time of p35/p25 protein levels in the spinal cord compared with behavioral responses to thermal and mechanical stimulation in streptozotocin (STZ)-induced diabetic rats. Additionally, we studied p35 expression when electroacupuncture (EA) and a sub-effective dose of NMDA (N-methyl-D-aspartate) receptor antagonist (MK-801) were used to treat hyperalgesia in the diabetic neuropathic pain (DNP). Thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were significantly decreased in the early stage of diabetes in rats. p35 expression after STZ injection gradually decreased from 1 week to 4 weeks compared to normal controls. p25 expression in 4-week diabetic rats was significantly higher than that of 2-week diabetic rats, and thermal PWL in 4-week diabetic rats showed delayed responses to painful thermal stimulation compared with those at 2 weeks. EA applied to the SP-9 point (2 Hz frequency) significantly prevented the thermal and mechanical hyperalgesia in the DNP rat. Additionally, EA combined with MK-801 prolonged anti-hyperalgesia, increased p35 expression, and decreased the cleavage of p35 to p25 during diabetic neuropathic pain. In this study we show EA combined with a sub-effective dose of MK-801 treatment in DNP induced by STZ that is related to p35/p25 expression in spinal cord.


Subject(s)
Animals , Rats , Acupuncture , Diabetic Neuropathies , Dizocilpine Maleate , Electroacupuncture , Hyperalgesia , N-Methylaspartate , Neuralgia , Spinal Cord , Streptozocin
16.
Indian J Physiol Pharmacol ; 2008 Jul-Sept; 52(3): 233-242
Article in English | IMSEAR | ID: sea-145872

ABSTRACT

Diabetic neuropathic pain is generally considered to be one of the most troublesome complications affecting diabetic patients and current therapy provides inadequate pain relief. In the present study, the effect of adenosine was investigated in a model of diabetic neuropathic pain. Diabetes was induced by streptozotocin (65 mg/kg, ip) in male Sprague Dawley rats and subjected to thermal (cold and hot) and chemical (formalin) stimuli. Diabetic rats developed hyperalgesia by the end of six weeks in thermal and chemical stimuli test. Adenosine (100, 200 and 500 mg/kg, ip) produced significant reversal of responses to thermal and chemical stimuli in diabetic rats. 8-Cyclopentyl-1, 3-dipropylxanthine (DPCPX 1 mg/kg, ip), an adenosine A1-receptor antagonist, but not 3,7-dimethyl-l-propargylxanthine (DMPX 1 mg/kg, ip), an adenosine A2A-receptor antagonist, reversed the protective effect of adenosine. These results indicate that adenosine is an effective analgesics in a model of diabetic neuropathy, and the protection produced by adenosine is via stimulation of adenosine A1-receptors.

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