Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplante...Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells(OECs) remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L4–5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L4–5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.展开更多
Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have b...Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have been administering continuous sciatic nerve block (CSNB) for patients with CLI whose pain could not be relieved by other analgesic tools. The aim of this retrospective study was to investigate the efficacy and safety of CSNB for patients with CLI. Method: We retrospectively investigated 99 patients who received CSNB for the relief of severe pain in the lower limb associated with CLI. Patient demographics, neurological history, complications, and subjective evaluation of the effectiveness of CSNB were investigated from their clinical records. The distal tips of 108 catheters were cultured. Result: One hundred and seventy-two catheters were placed in 99 patients. More than 90% of the patients enjoyed considerable relief of severe pain. The analgesic effect of CSNB was greater in patients with older age and hemodialysis. Thirty-one catheters had positive bacterial colonization. However, no severe infectious complication was found. There was no relationship between the co-existence of diabetes and positive bacterial colonization. We encountered a patient with ASO and diabetes who suffered from persistent motor weakness and hypesthesia even after 3 months of CSNB placement. Conclusions: CSNB provided good pain control for patients with severe pain caused by CLI. Although catheters were frequently found to be colonized, infection at the catheter site was self-limiting even in patients with diabetes.展开更多
BACKGROUND: Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 (GAP-43) in the spinal cord and dorsal root ganglion, local anesthetics bloc...BACKGROUND: Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 (GAP-43) in the spinal cord and dorsal root ganglion, local anesthetics blocking electrical impulse propagation of nerve fibers may also affect the expression of GAP-43 in the spinal cord and dorsal root ganglion. OBJECTIVE: To determine the effects of continuous peripheral nerve block by tetrodotoxin before and after nerve injury on GAP-43 expression in the dorsal root ganglion during the development of neuropathic pain. DESIGN: A randomized controlled animal experiment. SETTINGS: Department of Anesthesiology, the Second Hospital of Xiamen City; Department of Anesthesiology, the Second Affiliated Hospital of Shantou University Medical College. MATERIALS: Thirty-five Spragne Dawley (SD) rats, weighing 200 - 250 g, were randomly divided into four groups: control group (n =5), simple sciatic nerve transection group (n =10), peripheral nerve block before and after sciatic nerve transection groups (n =10). All the sciatic nerve transection groups were divided into two subgroups according to the different postoperative survival periods: 3 and 7 days (n =5) respectively. Mouse anti-GAP-43 monoclonal antibody (Sigma Co., Ltd.), supervision TM anti-mouse reagent (HRP, Changdao antibody diagnosis reagent Co., Ltd., Shanghai), and HMIAS-100 image analysis system (Qianping Image Engineering Company, Tongji Medical University) were employed in this study. METHODS: This experiment was carried out in the Department of Surgery and Pathological Laboratory, the Second Affiliated Hospital of Shantou University Medical College from April 2005 to April 2006. ①The animals were anesthetized and the right sciatic nerve was exposed and transected at 1 cm distal to sciatic notch. ② Tetrodotoxin 10 μg/kg was injected percutaneously between the greater trochanter and the posterior superior iliac spine of fight hind limb to block the sciatic nerve proximally at 1 hour before or 4 hours after nerve injury respectively, the injection was repeated in all the rats every 12 hours.③ At 3 or 7 days after nerve injury, immunohistochemistry and image analysis were used to evaluate the expression of GAP-43 in the dorsal root ganglions of L5 to the transected sciatic nerve, and quantitative analysis was also performed. ④ Statistical analysis was performed using one way analysis of variance followed by t test. MAIN OUTCOME MEASURE: Expression of GAP-43 in the fight dorsal root ganglions of L5. RESULTS: All the 35 SD rats were involved in the final analysis of results. In normal rats, there were very low expressions of GAP-43 in the dorsal root ganglions. In simple sciatic nerve transection rats 3 and 7 days after sciatic nerve transection, the average absorbance value of GAP-43 immunopositive neurons were significantly different from that in normal rats (t =8.806, 6.771, P 〈 0.01). Whereas 3 and 7 days after sciatic nerve transection in rats with peripheral nerve block before and after nerve injury, the average absorbance value of GAP-43 immunopositive neurons were not significantly different from that in normal rats (P 〉 0.05). CONCLUSION: Local anesthetic continuous peripheral nerve block before or after nerve injury can suppress nerve injury induced high expression of GAP-43 during the development of neuropathic pain.展开更多
Objective:To evaluate the effects of the standardized extract of fenugreek(Trigonella foenumgraecum L.Family:Leguminasae) seed(IND01) in animal models of peripheral neuropathy. Methods:IND01 was prepared from fenugree...Objective:To evaluate the effects of the standardized extract of fenugreek(Trigonella foenumgraecum L.Family:Leguminasae) seed(IND01) in animal models of peripheral neuropathy. Methods:IND01 was prepared from fenugreek seeds and standardized by high performance liquid chromatography to a marker compound,trigonelline.The effects of daily oral administration of IND01(50,100 and 200 mg/kg) were studied in rats after partial sciatic nerve ligation(PSNL) and sciatic nerve crush injury(SNCI) during 30-days period.The measurements on thermal hyperalgesia(TH),motor function test(MFT) score and motor nerve conduction velocity (MNCV) were recorded.Results:IND01 offered sustained protection against TH and deranged MFT scores in both models from 7-day onwards.Fifteen days of daily oral administration of IND01 restored MNCV reduction in rats with SNCI but not with PSNL.Conclusions:IND01 was found to be effective in rat models of painful peripheral neuropathy.展开更多
Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1(NMDAR1) plays an important role in t...Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1(NMDAR1) plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D(-)-2-amino-5-phosphonopentanoic acid(AP-5),or both once daily for 15 days.Compared with injured drug na?ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity(as assessed by immunohistochemistry) and protein(as determined by western blot assay) in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.展开更多
β-Caryophyllene (BCP) is known as a common constitute of the essential oils of numerous food plants and primary component in Cannabis. In this study, we investigated the effect of local intraplantar (i.pl.) injection...β-Caryophyllene (BCP) is known as a common constitute of the essential oils of numerous food plants and primary component in Cannabis. In this study, we investigated the effect of local intraplantar (i.pl.) injection of BCP on mechanical hypersensitivity induced by partial sciatic nerve ligation (PSNL) in mice. Relative to sham operation controls, mice with the PSNL displayed a maximum level of hyperresponsiveness to von Frey metallic filament on post-operative day 7. PSNL-induced allodynia was seen in the ipsilateral side of nerve ligation, but not in the contralateral side. The i.pl. injection of BCP into the ipsilateral hindpaw to PSNL attenuated mechanical allodynia in a dose-dependent manner. BCP injection into the contralateral hindpaw did not produce anti-allodynic effects, suggesting a local peripheral anti-allodynic effect of BCP. Anti-allodynic effects induced by i.pl. injection of BCP were prevented by pretreatment with the cannabinoid (CB2) receptor antagonist AM630, but not by the CB1 receptor antagonist AM251. These data suggest that i.pl. injection of BCP could produce anti-allodynia by activating peripheral CB2 receptors, but not CB1 receptors in a mouse model of neuropathic pain. Taken together, these results suggest that peripheral CB2 receptors may contribute to the effectiveness of BCP in the treatment of neuropathic pain disorders.展开更多
Background: Pneumatic arterial tourniquet is a very commonly used technique in limb surgeries to provide bloodless field to facilitate dissection and decrease blood loss. However, arterial tourniquet has many deleteri...Background: Pneumatic arterial tourniquet is a very commonly used technique in limb surgeries to provide bloodless field to facilitate dissection and decrease blood loss. However, arterial tourniquet has many deleterious effects including hemodynamic changes, serum lactate and potassium level changes and tourniquet-induced pain which sometimes can be severe and intolerable. Aim of the study: To evaluate the effect of different regional blocks: femoral-sciatic, spinal and epidural blocks on serum lactate and potassium levels and the degree of arterial tourniquet-induced pain in patients undergoing lower limb orthopedic surgeries. Methods: 60 patients underwent lower limb orthopedic surgery with application of tourniquet for duration not more than 90 minutes. Patients were assigned randomly to one of three groups (20 each) Group I had sciatic-femoral block, Group II: patients had spinal anesthesia and Group III: patients had epidural anesthesia. Intraoperative hemodynamics, changes in serum potassium and lactate levels and tourniquet pain after tourniquet inflation & deflation, were recorded. Results: There was no statistically significant difference among the three groups regarding tourniquet pain after tourniquet inflation (p = 0.872) and deflation (p = 0.902), and regarding serum levels changes of potassium (p = 0.067) and lactate (p = 0.051). However, each group showed statistically significant increase in post deflation tourniquet pain (p = 0.003, 0.002, 0.003, in groups F, S, E respectively) and serum potassium (p = 0.004, 0.006, 0.000, in groups F, S, E respectively) and lactate levels (p = 0.004, 0.000, 0.000, in groups F, S, E respectively) when compared to the pre-deflation values, and the increase was directly proportional to the duration of tourniquet. Conclusion: the three different types of anesthesia (femoral-sciatic, spinal and epidural block) have the same effect on serum lactate and potassium levels and the degree of tourniquet pain, which were related to the duration of tourniquet inflation.展开更多
Increased reactive oxygen species by the activation of NADPH oxidase(NOX) contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabe...Increased reactive oxygen species by the activation of NADPH oxidase(NOX) contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin(30 and 100 mg/kg per day,intragastrically) for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase(n NOS,i NOS),superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1(marker for increased microgliosis) in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity(Schwann cell marker) was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.展开更多
Background: The primary motor cortex (M1) stimulation (MCS) is a useful tool for attenuation of the peripheral neuropathic pain in patients with pharmacologically refractory pain. Furthermore, that neurological proced...Background: The primary motor cortex (M1) stimulation (MCS) is a useful tool for attenuation of the peripheral neuropathic pain in patients with pharmacologically refractory pain. Furthermore, that neurological procedure may also cause antinociception in rodents with neuropathic pain. Cold allodynia is a frequent clinical finding in patients with neuropathic pain, then, we evaluated if an adapted model of neuropathy induced by chronic constriction injury (CCI) of the ischiadicus nervus (sciatic nerve) produces cold allodynia in an animal model of chronic pain. In addition, we also investigated the effect of the electrical stimulation of the M1 on chronic neuropathic pain condition in laboratory animals. Methods: Male Wistar rats were used. An adapted model of peripheral mononeuropathy induced by CCI was carried out by placing a single loose ligature around the right sciatic nerve. The acetone test was used to evaluate the cold allodynia in CCI or Sham (without ligature) rats. The MCS (M1) was performed at low-frequency (20 μA, 100 Hz) during 15 s by deep brain stimulation (DBS-Thomas Recording device) 21 days after CCI or Sham procedures. The cold allodynia was measured before and immediately after the neurostimulation of M1 in the following time-window: 0, 15 and 30 min after MCS. Results: Cold allodynia threshold increased in animals with chronic neuropathic pain submitted to the acetone test 21 days after the CCI surgery. The M1-stimulation by DBS procedure decreased the cold allodynia immediately and until 30 min after M1-stimulation in rats with chronic neuropathic pain. Conclusion: The current proposal for a CCI model by a single loose ligature of the sciatic nerve can be employed as an experimental model of chronic neuropathic pain in rats submitted to peripheral nervous system injury. The M1-stimulation produced antinociception in rats with chronic neuropathic pain. Thus, we reinforced that the MCS decreases cold allodynia in laboratory animals submitted to persistent sciatic nerve constriction and can be a more reasonable procedure for the treatment of chronic intractable neuropathic pain.展开更多
Schwann cell transplantation is a promising method to promote neural repair, and can be used for peripheral nerve protection and myelination. Microcapsule technology largely mitigates immune rejection of transplanted ...Schwann cell transplantation is a promising method to promote neural repair, and can be used for peripheral nerve protection and myelination. Microcapsule technology largely mitigates immune rejection of transplanted cells. We previously showed that microencapsulated olfactory ensheathing cells can reduce neuropathic pain and we hypothesized that microencapsulated Schwann cells can also inhibit neuropathic pain. Rat Schwann cells were cultured by subculture and then microencapsulated and were tested using a rat chronic constriction injury(CCI) neuropathic pain model. CCI rats were treated with Schwann cells or microencapsulated Schwann cells and were compared with sham and CCI groups. Mechanical withdrawal threshold and thermal withdrawal latency were assessed preoperatively and at 1, 3, 5, 7, 9, 11 and 14 days postoperatively. The expression of P2X3 receptors in L4-5 dorsal root ganglia of the different groups was detected by double-label immunofluorescence on day 14 after surgery. Compared with the chronic constriction injury group, mechanical withdrawal threshold and thermal withdrawal latency were higher, but the expression of P2X3 receptors was remarkably decreased in rats treated with Schwann cells and microencapsulated Schwann cells, especially in the rats transplanted with microencapsulated Schwann cells. The above data show that microencapsulated Schwann cell transplantation inhibits P2X3 receptor expression in L4-5 dorsal root ganglia and neuropathic pain.展开更多
基金supported by the National Natural Science Foundation of China,No.81260190the Natural Science Foundation of Jiangxi Province of China,No.20132BAB205023+1 种基金a grant from the Science and Technology Research Program of Department of Education of Jiangxi Province in China,No.GJJ13159a grant from the Science and Technology Program of Department of Health of Jiangxi Province,No.20132019
文摘Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells(OECs) remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L4–5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L4–5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.
文摘Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have been administering continuous sciatic nerve block (CSNB) for patients with CLI whose pain could not be relieved by other analgesic tools. The aim of this retrospective study was to investigate the efficacy and safety of CSNB for patients with CLI. Method: We retrospectively investigated 99 patients who received CSNB for the relief of severe pain in the lower limb associated with CLI. Patient demographics, neurological history, complications, and subjective evaluation of the effectiveness of CSNB were investigated from their clinical records. The distal tips of 108 catheters were cultured. Result: One hundred and seventy-two catheters were placed in 99 patients. More than 90% of the patients enjoyed considerable relief of severe pain. The analgesic effect of CSNB was greater in patients with older age and hemodialysis. Thirty-one catheters had positive bacterial colonization. However, no severe infectious complication was found. There was no relationship between the co-existence of diabetes and positive bacterial colonization. We encountered a patient with ASO and diabetes who suffered from persistent motor weakness and hypesthesia even after 3 months of CSNB placement. Conclusions: CSNB provided good pain control for patients with severe pain caused by CLI. Although catheters were frequently found to be colonized, infection at the catheter site was self-limiting even in patients with diabetes.
基金the Natural Science Foundation of Guangdong Province, No.034628
文摘BACKGROUND: Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 (GAP-43) in the spinal cord and dorsal root ganglion, local anesthetics blocking electrical impulse propagation of nerve fibers may also affect the expression of GAP-43 in the spinal cord and dorsal root ganglion. OBJECTIVE: To determine the effects of continuous peripheral nerve block by tetrodotoxin before and after nerve injury on GAP-43 expression in the dorsal root ganglion during the development of neuropathic pain. DESIGN: A randomized controlled animal experiment. SETTINGS: Department of Anesthesiology, the Second Hospital of Xiamen City; Department of Anesthesiology, the Second Affiliated Hospital of Shantou University Medical College. MATERIALS: Thirty-five Spragne Dawley (SD) rats, weighing 200 - 250 g, were randomly divided into four groups: control group (n =5), simple sciatic nerve transection group (n =10), peripheral nerve block before and after sciatic nerve transection groups (n =10). All the sciatic nerve transection groups were divided into two subgroups according to the different postoperative survival periods: 3 and 7 days (n =5) respectively. Mouse anti-GAP-43 monoclonal antibody (Sigma Co., Ltd.), supervision TM anti-mouse reagent (HRP, Changdao antibody diagnosis reagent Co., Ltd., Shanghai), and HMIAS-100 image analysis system (Qianping Image Engineering Company, Tongji Medical University) were employed in this study. METHODS: This experiment was carried out in the Department of Surgery and Pathological Laboratory, the Second Affiliated Hospital of Shantou University Medical College from April 2005 to April 2006. ①The animals were anesthetized and the right sciatic nerve was exposed and transected at 1 cm distal to sciatic notch. ② Tetrodotoxin 10 μg/kg was injected percutaneously between the greater trochanter and the posterior superior iliac spine of fight hind limb to block the sciatic nerve proximally at 1 hour before or 4 hours after nerve injury respectively, the injection was repeated in all the rats every 12 hours.③ At 3 or 7 days after nerve injury, immunohistochemistry and image analysis were used to evaluate the expression of GAP-43 in the dorsal root ganglions of L5 to the transected sciatic nerve, and quantitative analysis was also performed. ④ Statistical analysis was performed using one way analysis of variance followed by t test. MAIN OUTCOME MEASURE: Expression of GAP-43 in the fight dorsal root ganglions of L5. RESULTS: All the 35 SD rats were involved in the final analysis of results. In normal rats, there were very low expressions of GAP-43 in the dorsal root ganglions. In simple sciatic nerve transection rats 3 and 7 days after sciatic nerve transection, the average absorbance value of GAP-43 immunopositive neurons were significantly different from that in normal rats (t =8.806, 6.771, P 〈 0.01). Whereas 3 and 7 days after sciatic nerve transection in rats with peripheral nerve block before and after nerve injury, the average absorbance value of GAP-43 immunopositive neurons were not significantly different from that in normal rats (P 〉 0.05). CONCLUSION: Local anesthetic continuous peripheral nerve block before or after nerve injury can suppress nerve injury induced high expression of GAP-43 during the development of neuropathic pain.
文摘Objective:To evaluate the effects of the standardized extract of fenugreek(Trigonella foenumgraecum L.Family:Leguminasae) seed(IND01) in animal models of peripheral neuropathy. Methods:IND01 was prepared from fenugreek seeds and standardized by high performance liquid chromatography to a marker compound,trigonelline.The effects of daily oral administration of IND01(50,100 and 200 mg/kg) were studied in rats after partial sciatic nerve ligation(PSNL) and sciatic nerve crush injury(SNCI) during 30-days period.The measurements on thermal hyperalgesia(TH),motor function test(MFT) score and motor nerve conduction velocity (MNCV) were recorded.Results:IND01 offered sustained protection against TH and deranged MFT scores in both models from 7-day onwards.Fifteen days of daily oral administration of IND01 restored MNCV reduction in rats with SNCI but not with PSNL.Conclusions:IND01 was found to be effective in rat models of painful peripheral neuropathy.
基金supported by the Youth Shihezi University Applied Basic Research Project of China,No.2015ZRKYQ-LH19
文摘Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1(NMDAR1) plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D(-)-2-amino-5-phosphonopentanoic acid(AP-5),or both once daily for 15 days.Compared with injured drug na?ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity(as assessed by immunohistochemistry) and protein(as determined by western blot assay) in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.
文摘β-Caryophyllene (BCP) is known as a common constitute of the essential oils of numerous food plants and primary component in Cannabis. In this study, we investigated the effect of local intraplantar (i.pl.) injection of BCP on mechanical hypersensitivity induced by partial sciatic nerve ligation (PSNL) in mice. Relative to sham operation controls, mice with the PSNL displayed a maximum level of hyperresponsiveness to von Frey metallic filament on post-operative day 7. PSNL-induced allodynia was seen in the ipsilateral side of nerve ligation, but not in the contralateral side. The i.pl. injection of BCP into the ipsilateral hindpaw to PSNL attenuated mechanical allodynia in a dose-dependent manner. BCP injection into the contralateral hindpaw did not produce anti-allodynic effects, suggesting a local peripheral anti-allodynic effect of BCP. Anti-allodynic effects induced by i.pl. injection of BCP were prevented by pretreatment with the cannabinoid (CB2) receptor antagonist AM630, but not by the CB1 receptor antagonist AM251. These data suggest that i.pl. injection of BCP could produce anti-allodynia by activating peripheral CB2 receptors, but not CB1 receptors in a mouse model of neuropathic pain. Taken together, these results suggest that peripheral CB2 receptors may contribute to the effectiveness of BCP in the treatment of neuropathic pain disorders.
文摘Background: Pneumatic arterial tourniquet is a very commonly used technique in limb surgeries to provide bloodless field to facilitate dissection and decrease blood loss. However, arterial tourniquet has many deleterious effects including hemodynamic changes, serum lactate and potassium level changes and tourniquet-induced pain which sometimes can be severe and intolerable. Aim of the study: To evaluate the effect of different regional blocks: femoral-sciatic, spinal and epidural blocks on serum lactate and potassium levels and the degree of arterial tourniquet-induced pain in patients undergoing lower limb orthopedic surgeries. Methods: 60 patients underwent lower limb orthopedic surgery with application of tourniquet for duration not more than 90 minutes. Patients were assigned randomly to one of three groups (20 each) Group I had sciatic-femoral block, Group II: patients had spinal anesthesia and Group III: patients had epidural anesthesia. Intraoperative hemodynamics, changes in serum potassium and lactate levels and tourniquet pain after tourniquet inflation & deflation, were recorded. Results: There was no statistically significant difference among the three groups regarding tourniquet pain after tourniquet inflation (p = 0.872) and deflation (p = 0.902), and regarding serum levels changes of potassium (p = 0.067) and lactate (p = 0.051). However, each group showed statistically significant increase in post deflation tourniquet pain (p = 0.003, 0.002, 0.003, in groups F, S, E respectively) and serum potassium (p = 0.004, 0.006, 0.000, in groups F, S, E respectively) and lactate levels (p = 0.004, 0.000, 0.000, in groups F, S, E respectively) when compared to the pre-deflation values, and the increase was directly proportional to the duration of tourniquet. Conclusion: the three different types of anesthesia (femoral-sciatic, spinal and epidural block) have the same effect on serum lactate and potassium levels and the degree of tourniquet pain, which were related to the duration of tourniquet inflation.
基金supported by the Research Fund of Ege University(Project No.2010-TIP-076)
文摘Increased reactive oxygen species by the activation of NADPH oxidase(NOX) contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin(30 and 100 mg/kg per day,intragastrically) for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase(n NOS,i NOS),superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1(marker for increased microgliosis) in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity(Schwann cell marker) was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.
文摘Background: The primary motor cortex (M1) stimulation (MCS) is a useful tool for attenuation of the peripheral neuropathic pain in patients with pharmacologically refractory pain. Furthermore, that neurological procedure may also cause antinociception in rodents with neuropathic pain. Cold allodynia is a frequent clinical finding in patients with neuropathic pain, then, we evaluated if an adapted model of neuropathy induced by chronic constriction injury (CCI) of the ischiadicus nervus (sciatic nerve) produces cold allodynia in an animal model of chronic pain. In addition, we also investigated the effect of the electrical stimulation of the M1 on chronic neuropathic pain condition in laboratory animals. Methods: Male Wistar rats were used. An adapted model of peripheral mononeuropathy induced by CCI was carried out by placing a single loose ligature around the right sciatic nerve. The acetone test was used to evaluate the cold allodynia in CCI or Sham (without ligature) rats. The MCS (M1) was performed at low-frequency (20 μA, 100 Hz) during 15 s by deep brain stimulation (DBS-Thomas Recording device) 21 days after CCI or Sham procedures. The cold allodynia was measured before and immediately after the neurostimulation of M1 in the following time-window: 0, 15 and 30 min after MCS. Results: Cold allodynia threshold increased in animals with chronic neuropathic pain submitted to the acetone test 21 days after the CCI surgery. The M1-stimulation by DBS procedure decreased the cold allodynia immediately and until 30 min after M1-stimulation in rats with chronic neuropathic pain. Conclusion: The current proposal for a CCI model by a single loose ligature of the sciatic nerve can be employed as an experimental model of chronic neuropathic pain in rats submitted to peripheral nervous system injury. The M1-stimulation produced antinociception in rats with chronic neuropathic pain. Thus, we reinforced that the MCS decreases cold allodynia in laboratory animals submitted to persistent sciatic nerve constriction and can be a more reasonable procedure for the treatment of chronic intractable neuropathic pain.
基金supported by the National Natural Science Foundation of China,No.81760418 and 81260190the Natural Science Foundation of Jiangxi Province,No.20132BAB205023,20151BAB205022+1 种基金a grant from Science and Technology Research Project of Jiangxi Education Department,No.GJJ13159a grant from the Science and Technology Program of Department of Health of Jiangxi Province,No.20173010
文摘Schwann cell transplantation is a promising method to promote neural repair, and can be used for peripheral nerve protection and myelination. Microcapsule technology largely mitigates immune rejection of transplanted cells. We previously showed that microencapsulated olfactory ensheathing cells can reduce neuropathic pain and we hypothesized that microencapsulated Schwann cells can also inhibit neuropathic pain. Rat Schwann cells were cultured by subculture and then microencapsulated and were tested using a rat chronic constriction injury(CCI) neuropathic pain model. CCI rats were treated with Schwann cells or microencapsulated Schwann cells and were compared with sham and CCI groups. Mechanical withdrawal threshold and thermal withdrawal latency were assessed preoperatively and at 1, 3, 5, 7, 9, 11 and 14 days postoperatively. The expression of P2X3 receptors in L4-5 dorsal root ganglia of the different groups was detected by double-label immunofluorescence on day 14 after surgery. Compared with the chronic constriction injury group, mechanical withdrawal threshold and thermal withdrawal latency were higher, but the expression of P2X3 receptors was remarkably decreased in rats treated with Schwann cells and microencapsulated Schwann cells, especially in the rats transplanted with microencapsulated Schwann cells. The above data show that microencapsulated Schwann cell transplantation inhibits P2X3 receptor expression in L4-5 dorsal root ganglia and neuropathic pain.