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
Objective:Pain from herniated disc is a common type of neuropathic pain.This study investigated whether electroacupuncture (EA) stimulation at distal-proximal combinations of acupoints in the rat model of neuropathic ...Objective:Pain from herniated disc is a common type of neuropathic pain.This study investigated whether electroacupuncture (EA) stimulation at distal-proximal combinations of acupoints in the rat model of neuropathic pain modulates spinal interleukin-1 beta (IL-1β) to induce acupuncture analgesia and possibly serve as a pain-relief modality for herniated disc.Methods:A rat model of neuropathic pain was established.Rats were randomly divided into normal,model,sham,EA 1,EA 2,and EA 3 groups.EA 1 rats were needled at bilateral ExB2,BL25,BL40,and BL60 acupoints.EA 2 rats Were needled at bilateral BL40 and BL60.EA 3 rats were needled at bilateral L5 Ex-B2 and BL25.EA stimulation was administered once daily over 7 days.Mechanical withdrawal threshold from noxious mechanical stimulation was measured 1 day preoperatively and at 3,5,and7 days postoperatively.After 7 days of intervention,enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-1β in the spinal cord.Results:Mechanical withdrawal threshold of rats in the model group decreased at 3 days postoperatively when compared with the normal group (P < 0.01),lasting 7 days postoperatively.Mechanical withdrawal thresholds in the EA 1,EA 2,and EA 3 groups were elevated over the model group (P < 0.05;P < 0.01).No obvious differences were found between EA 1,EA 2,and EA 3 groups.ELISA demonstrated an increase in IL-1β in the spinal cord of rats in the model group compared with the normal group (P < 0.01).EA treatment attenuated the increase in spinal IL-1β in the model group.Expression of spinal IL-1β was significantly lower in EA 1,EA 2,and EA 3 groups.Conclusion:EA at distal + proximal acupoints,distal points,as well as proximal points attenuated upregulation of spinal IL-1β,alleviated the extent of neuropathic pain hypersensitivity,and promoted mechanical withdrawal threshold,resulting in EA analgesia.展开更多
Objective: When nerve injury or inflammatory injury, different miRNA-mediated signal pathways are activated or inactivated, causing pain or hyperalgesia. Therefore, miRNA has become a new direction of pain mechanism r...Objective: When nerve injury or inflammatory injury, different miRNA-mediated signal pathways are activated or inactivated, causing pain or hyperalgesia. Therefore, miRNA has become a new direction of pain mechanism research. We aimed to investigate the effect and mechanism of miR-362-3p on neuropathic pain in rats with chronic sciatic nerve injury (CCI). Methods: Neuropathic pain CCI rat model was established. Real-time-quantitative polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, intrathecal injection, Enzyme-linked immunosorbent assay (ELISA), and dual luciferase reporter gene assays were used to explore the role of miR-362-3p in neuropathic pain development and the relationship between miR-362-3p and JMJD1A (Jumonji domain-containing 1A). Results: In the CCI group, the miR-362-3p level was increased and JMJD1A level was reduced in spinal cords and isolated microglia. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) values were increased, the secretion of inflammatory factors was reduced, and the microglial marker Iba1 expression was decreased after intrathecal administration of miR-362-3p. miR-362-3p was observed to target JMJD1A. JMJD1A elevation abolished the inhibitory effects of miR-362-3p on neuropathic pain development. Conclusion: Intrathecal administration of miR-362-3p significantly relieved neuropathic pain in CCI rats and inhibited neuroinflammation possibly through regulating JMJD1A.展开更多
Background Pain physicians pay close attention to neuropathic pain （NP）,since there is currently no ideal treatment.Radial shock wave therapy （RSWT） is a noninvasive treatment to chronic pain of soft tissue disord...Background Pain physicians pay close attention to neuropathic pain （NP）,since there is currently no ideal treatment.Radial shock wave therapy （RSWT） is a noninvasive treatment to chronic pain of soft tissue disorders.So far,there is no information on the use of RSWT for the treatment of NP.Therefore we observe the effects of RSWT on a NP model induced by chronic constriction injury （CCI） in rats.Methods Four different energy densities （1.0,1.5,2.0 and 2.5 bar） RSWT administered as a single session or repeated sessions in rats with NP induced by CCI of the sciatic nerve.The analgesic effect was assessed by measuring mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL）.The safety was assessed through calculating sciatic functional index （SFI）.Results MWT and TWL increased after a single session of RSWT from day 1 to day 5 but retumed to baseline levels by day 10.Following repeated sessions of RSWT,both the MWT and TWL were significantly higher than NP group （P ＜ 0.01）for at least 4 weeks.In addition,no significant changes of SFI were observed in any groups after repeated sessions of RSWT and no increased pain or other side effects in any animals.Conclusions A single session of RSWT is rapidly effective in the treatment of CCI,but the efficacy maintained in a short period.However,repeated sessions of RSWT have prolonged efficacy.展开更多
AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesi...AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.展开更多
Microglia can modulate spinal nociceptive transmission.Yet,their role in spinal cord stimulation(SCS)-induced pain inhibition is unclear.Here,we examined how SCS affects microglial activation in the lumbar cord of rat...Microglia can modulate spinal nociceptive transmission.Yet,their role in spinal cord stimulation(SCS)-induced pain inhibition is unclear.Here,we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury(CCI)of the sciatic nerve.Male rats received conventional SCS(50 Hz,80%motor threshold,180 min,2 sessions/day)or sham stimulation on days 18-20 post-CCI.SCS transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal horns.SCS also upregulated the mRNAs of Ml-like markers,but not M2-like markers.Inducible NOS protein expression was increased,but brain-derived neurotrophic factor was decreased after SCS.Intrathecal minocycline(1μg-100μg),which inhibits microglial activation,dosedependently attenuated the mechanical hypersensitivity.Pretreatment with low-dose minocycline(1μg,30 min)prolonged the SCS-induced pain inhibition.These findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain.展开更多
Background: Mechanical ventilation (hit one) during surgery (hit two) is often needed and both induce an inflammatory response. Dysregulation of the inflammatory response can cause chronic postoperative pain. Methods:...Background: Mechanical ventilation (hit one) during surgery (hit two) is often needed and both induce an inflammatory response. Dysregulation of the inflammatory response can cause chronic postoperative pain. Methods: Healthy C57BL6 mice (n = 56) were mechanically ventilated (MV) and allocated to receive sham (MV-sham) or mechanically ventilation with chronic constriction injury (MV-CCI) surgery in the left hind paw. Plasma interleukin (IL)-1β, IL-6, IL-10, keratinocyte derived chemokine (KC) and tumor necrosis factor (TNF)-α were determined on day 0 and 16. Sensory testing was performed on day 0, 3, 7 and 16 by cold plate test (number of lifts (NOL) and cumulative reaction time (CRT)) and von Frey test. The effect of lidocaine on cytokines and sensory testing was analyzed. Results: MV-Sham showed an increase in IL-1β and TNF-α, and MV- CCI-lido increased levels of KC compared with MV on day 0. No difference in cytokine levels was observed on day 16. NOL of the left paw versus the right was increased in MV-CCI on day 7, and in MV-CCI-lido on day 7 and 16. The NOL of the left paw was decreased in MV-sham and MV-CCI-lido compared with MV-CCI on day 16. The CRT of the left paw was increased for MV-CCI on day 3 and 7, and for MV-CCI-lido on day 7. On day 16, MV-sham and MV-CCI-lido showed a decreased CRT of the left paw compared with MV-CCI. Conclusion: Nerve injury and not systemic inflammatory response seems mandatory for development of neuropathic pain in this “two-hit” model. Lidocaine attenuates cold allodynia in mice.展开更多
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This study was supported by grants from the Project of Beijing University of Chinese Medicine in China(No.JYB22 e JS022).
文摘Objective:Pain from herniated disc is a common type of neuropathic pain.This study investigated whether electroacupuncture (EA) stimulation at distal-proximal combinations of acupoints in the rat model of neuropathic pain modulates spinal interleukin-1 beta (IL-1β) to induce acupuncture analgesia and possibly serve as a pain-relief modality for herniated disc.Methods:A rat model of neuropathic pain was established.Rats were randomly divided into normal,model,sham,EA 1,EA 2,and EA 3 groups.EA 1 rats were needled at bilateral ExB2,BL25,BL40,and BL60 acupoints.EA 2 rats Were needled at bilateral BL40 and BL60.EA 3 rats were needled at bilateral L5 Ex-B2 and BL25.EA stimulation was administered once daily over 7 days.Mechanical withdrawal threshold from noxious mechanical stimulation was measured 1 day preoperatively and at 3,5,and7 days postoperatively.After 7 days of intervention,enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-1β in the spinal cord.Results:Mechanical withdrawal threshold of rats in the model group decreased at 3 days postoperatively when compared with the normal group (P < 0.01),lasting 7 days postoperatively.Mechanical withdrawal thresholds in the EA 1,EA 2,and EA 3 groups were elevated over the model group (P < 0.05;P < 0.01).No obvious differences were found between EA 1,EA 2,and EA 3 groups.ELISA demonstrated an increase in IL-1β in the spinal cord of rats in the model group compared with the normal group (P < 0.01).EA treatment attenuated the increase in spinal IL-1β in the model group.Expression of spinal IL-1β was significantly lower in EA 1,EA 2,and EA 3 groups.Conclusion:EA at distal + proximal acupoints,distal points,as well as proximal points attenuated upregulation of spinal IL-1β,alleviated the extent of neuropathic pain hypersensitivity,and promoted mechanical withdrawal threshold,resulting in EA analgesia.
文摘Objective: When nerve injury or inflammatory injury, different miRNA-mediated signal pathways are activated or inactivated, causing pain or hyperalgesia. Therefore, miRNA has become a new direction of pain mechanism research. We aimed to investigate the effect and mechanism of miR-362-3p on neuropathic pain in rats with chronic sciatic nerve injury (CCI). Methods: Neuropathic pain CCI rat model was established. Real-time-quantitative polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, intrathecal injection, Enzyme-linked immunosorbent assay (ELISA), and dual luciferase reporter gene assays were used to explore the role of miR-362-3p in neuropathic pain development and the relationship between miR-362-3p and JMJD1A (Jumonji domain-containing 1A). Results: In the CCI group, the miR-362-3p level was increased and JMJD1A level was reduced in spinal cords and isolated microglia. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) values were increased, the secretion of inflammatory factors was reduced, and the microglial marker Iba1 expression was decreased after intrathecal administration of miR-362-3p. miR-362-3p was observed to target JMJD1A. JMJD1A elevation abolished the inhibitory effects of miR-362-3p on neuropathic pain development. Conclusion: Intrathecal administration of miR-362-3p significantly relieved neuropathic pain in CCI rats and inhibited neuroinflammation possibly through regulating JMJD1A.
文摘Background Pain physicians pay close attention to neuropathic pain （NP）,since there is currently no ideal treatment.Radial shock wave therapy （RSWT） is a noninvasive treatment to chronic pain of soft tissue disorders.So far,there is no information on the use of RSWT for the treatment of NP.Therefore we observe the effects of RSWT on a NP model induced by chronic constriction injury （CCI） in rats.Methods Four different energy densities （1.0,1.5,2.0 and 2.5 bar） RSWT administered as a single session or repeated sessions in rats with NP induced by CCI of the sciatic nerve.The analgesic effect was assessed by measuring mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL）.The safety was assessed through calculating sciatic functional index （SFI）.Results MWT and TWL increased after a single session of RSWT from day 1 to day 5 but retumed to baseline levels by day 10.Following repeated sessions of RSWT,both the MWT and TWL were significantly higher than NP group （P ＜ 0.01）for at least 4 weeks.In addition,no significant changes of SFI were observed in any groups after repeated sessions of RSWT and no increased pain or other side effects in any animals.Conclusions A single session of RSWT is rapidly effective in the treatment of CCI,but the efficacy maintained in a short period.However,repeated sessions of RSWT have prolonged efficacy.
基金the National Natural Science Foundation of China(No.30470559,30330230,30240059)the National Basic Research Development Program(973)of China(No.2007CB512501)Beijing Natural Science Foundation(No.7052039)
文摘Dorsal root ganglion(DRG)neurons have peripheral terminals in skin,muscle,and other peripheral tissues,andcentral
基金the Research Institute of Veterinary Science,College of Veterinary Medieine,Seoul National University
文摘AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.
基金the Neurosurgery Pain Research Institute at the Johns Hopkins University and subsidized by the National Institutes of Health(Bethesda,Maryland,USA)(NS 110598)supported by an award from the China Scholarship Council for Chinese PhD candidates to study abroad。
文摘Microglia can modulate spinal nociceptive transmission.Yet,their role in spinal cord stimulation(SCS)-induced pain inhibition is unclear.Here,we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury(CCI)of the sciatic nerve.Male rats received conventional SCS(50 Hz,80%motor threshold,180 min,2 sessions/day)or sham stimulation on days 18-20 post-CCI.SCS transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal horns.SCS also upregulated the mRNAs of Ml-like markers,but not M2-like markers.Inducible NOS protein expression was increased,but brain-derived neurotrophic factor was decreased after SCS.Intrathecal minocycline(1μg-100μg),which inhibits microglial activation,dosedependently attenuated the mechanical hypersensitivity.Pretreatment with low-dose minocycline(1μg,30 min)prolonged the SCS-induced pain inhibition.These findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain.
文摘Background: Mechanical ventilation (hit one) during surgery (hit two) is often needed and both induce an inflammatory response. Dysregulation of the inflammatory response can cause chronic postoperative pain. Methods: Healthy C57BL6 mice (n = 56) were mechanically ventilated (MV) and allocated to receive sham (MV-sham) or mechanically ventilation with chronic constriction injury (MV-CCI) surgery in the left hind paw. Plasma interleukin (IL)-1β, IL-6, IL-10, keratinocyte derived chemokine (KC) and tumor necrosis factor (TNF)-α were determined on day 0 and 16. Sensory testing was performed on day 0, 3, 7 and 16 by cold plate test (number of lifts (NOL) and cumulative reaction time (CRT)) and von Frey test. The effect of lidocaine on cytokines and sensory testing was analyzed. Results: MV-Sham showed an increase in IL-1β and TNF-α, and MV- CCI-lido increased levels of KC compared with MV on day 0. No difference in cytokine levels was observed on day 16. NOL of the left paw versus the right was increased in MV-CCI on day 7, and in MV-CCI-lido on day 7 and 16. The NOL of the left paw was decreased in MV-sham and MV-CCI-lido compared with MV-CCI on day 16. The CRT of the left paw was increased for MV-CCI on day 3 and 7, and for MV-CCI-lido on day 7. On day 16, MV-sham and MV-CCI-lido showed a decreased CRT of the left paw compared with MV-CCI. Conclusion: Nerve injury and not systemic inflammatory response seems mandatory for development of neuropathic pain in this “two-hit” model. Lidocaine attenuates cold allodynia in mice.
