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Objective To evaluate the relationship between hippocampal cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway and cognitive dysfunction in rats with chronic pathological pain.Methods Thirty-two healthy adult male Sprague-Dawley rats,weighing 220-250 g,were divided into 3 groups using a random number table:control group(group C,n=8),sham operation group(group S,n=8)and chronic pathological pain group(group CP,n=16).Chronic pathological pain model was established by injecting cobra venom 0.4 mg(4 μl)into the sheath of the infraorbital nerve.The mechanical pain threshold was measured at 3 days before establishment of the model(baseline)and 4 days and 1,2,3,4 and 8 weeks after establishment of the model.Morris water maze test was performed to evaluate the spatial learning and memory abilities at 5 and 9 weeks after establishment of the model.Eight rats were sacrificed at 5 and 9 weeks after establishment of the model in CP group,and rats were sacrificed after the end of Morris water maze test at 9 weeks after establishment of the model in C and S groups.The hippocampi were isolated for determination of the expression of phosphorylated CREB and BDNF in the hippocampal tissues using Western blot.Results Compared with group C,the mechanical pain threshold was significantly decreased at each time point after establishment of the model,the escape latency was prolonged at 5 and 9 weeks after establishment of the model,the rate of time of staying at the target quadrant was decreased,the frequency of crossing the original platform was decreased,and the expression of phosphorylated CREB and BDNF was down-regulated at 9 weeks after establishment of the model in group CP(P0.05).Conclusion The mechanism underlying cognitive dysfunction may be related to inhibited activation of CREB/BDNF signaling pathway in the hippocampus of rats with chronic pathological pain.
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Objective To evaluate the analgesic effect of curcumin on trigeminal neuralgia in rats. Methods Thirty healthy adult male Sprague?Dawley rats, weighing 200-250 g, aged 7-8 weeks, were divided into 3 groups ( n=10 each) using a random number table: sham operation group ( group S) , tri?geminal neuralgia group (group TN) and trigeminal neuralgia + curcumin group (group Cur). Trigeminal neuralgia model was established by injecting cobra venom solution into the sheath of the infraorbital nerve ( ION) . Starting from 15 days after establishment of the model, curcumin 45 mg∕kg was intragastrically ad?ministered twice a day for 28 consecutive days in group Cur, while the equal volume of peanut oil was ad?ministered in group TN. Before establishment of the model (baseline), and on 4, 7, 14, 21, 28, 35 and 42 days after establishment of the model, the mechanical pain threshold was measured, the free behav?iors were observed, and the time and frequency of face?grooming and exploratory behaviors were recorded. After observation of the free behaviors, the ION and medulla oblongata on the affected side were removed for examination of the ultrastructure using transmission electron microscopy. Results Compared with group S, the mechanical pain threshold was significantly decreased, the time of face?grooming behaviors was signifi?cantly prolonged, the frequency of face?grooming behaviors was significantly increased, the time of explora?tory behaviors was significantly shortened, and the frequency of exploratory behaviors was significantly de?creased on 4-42 days after establishment of the model in group TN (P<0.05 or 0.01). Compared with group TN, the mechanical pain threshold was significantly increased, and the time of face?grooming behav?iors was significantly shortened on 28-42 days after establishment of the model, and the frequency of face?grooming behaviors was significantly decreased, the time of exploratory behaviors was significantly pro?longed, and the frequency of exploratory behaviors was significantly increased on 21-42 days after estab?lishment of the model in group Cur ( P<0.05 or 0.01) . Microscopic examination revealed that the changes in demyelination of the ION and medulla oblongata were significantly attenuated in group Cur as compared with group TN. Conclusion Intragastrically administered curcumin 45 mg∕kg ( twice a day for 28 consecutive days) can attenuate trigeminal neuralgia in rats, and the mechanism is related to the attenuated changes in demyelination of the ION and medulla oblongata.
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Objective To evaluate the effect of curcumin on cognitive dysfunction in a rat model of trigeminal neuralgia.Methods Thirty healthy adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 3 groups (n=10 each) using a random number table:sham operation group (Sham group),trigeminal neuralgia group (TN group),and trigeminal neuralgia + curcumin group (TN + Cur group).Trigeminal neuralgia was produced by injecting cobra venom solution 4 μl into the sheath of the infraorbital nerve in TN and TN + Cur groups.Starting from 15 days after establishment of the model,1.5 ml peanut oil was injected through a gastric tube into stomach twice a day (in the morning and at night) for 28 consecutive days in TN group,and curcumin 45 mg/kg (dissolved in 1.5 ml peanut oil) was injected through a gastric tube into stomach twice a day (in the morning and at night) for 28 consecutive days in TN + Cur group.The cognitive function was assessed using Morris water maze test after the end of treatment.The escape latency,swimming speed,ratio of time of staying at the target quadrant,and the number of times the animals crossing the platform were recorded.The pathological changes in the hippocampal CA1 region were observed with an electron microscope.The ultrastructure of neurons,organelles and synapses in the hippocampal CA1 region was examined with a transmission electron microscope.Results There was no significant difference in the swimming speed between the three groups (P＞0.05).Compared with Sham group,the escape latency on 1st-4th days was significantly prolonged,the ratio of time of staying at the target quadrant was decreased,and the number of times the animals crossing the platform was decreased in TN group,and the escape latency was significantly prolonged on 3rd and 4th days in TN + Cur group (P＜0.01).Compared with TN group,the escape latency on 2nd-4th days was significantly shortened,the ratio of time of staying at the target quadrant was increased,the number of times the animals crossing the platform was increased (P＜0.01),and the pathological changes of hippocampal tissues were attenuated in TN + Cur group.Conclusion Curcumin can improve cognitive dysfunction in a rat model of trigeminal neuralgia.
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Objective To investigate the effect of lipoxin A4 LXA4) on radicular pain caused by intervertebral disc herniation.Methods Non-compressive intervertebral disc herniation was induced into forty-eight adult male Sprague-Dawley rats,and they were divided into a sham group (sham operation + 10 μl normal saline),a control group (modeled + 10 μl normal saline),an LXA4 10 ng group (modeled + 10 ng LXA4) and an LXA4 100 ng group (modeled + 100 ng LXA4),with 12 rats in each group.The normal saline (10 μl) or LXA4 (10 μl) was administered intrathecally right after the operation and on each of the three succeeding days.General behavior was observed and the 50％ paw withdrawal threshold (50％ PWT) was measured.On postoperative day 7 all the rats were killed and the ipsilateral lumbar (L4~) segments of their spinal dorsal horns were removed for determination of the expression of p-JNK,t-JNK,p-ERK and t-ERK proteins using western blotting.TNF-α,IL-1β and TGF-β1 expression were determined using ELISA.Results There was no significant difference in the 50％PWT of the sham group before and after surgery,but the 50％ PWTs of the control group and the LXA4 10 ng group were significantly decreased after the operation compared with their values beforehand and significantly lower than the value of the sham group at all time points.Moreover,the 50％ PWT of the LXA4 10 ng group on postoperative days 3 and 5 was significantly higher than the control group;as was the value of the LXA4 100 ng group on postoperative days 2,3,4,5,6 and 7.The p-JNK and p-ERK expression in the control group,the LXA4 10 ng group and the LXA4 100 ng group were all increased significantly more than in the sham group,but their expression in the LXA4 10 ng group and LXA4 100 ng group were decreased significantly more in a dose-dependent manner compared with the control group,with the LXA4 100 ng group showing the greatest decrease.There were no significant differences in t-JNK or t-ERK expression within each group.Conclusion LXA4 can alleviate radicular pain caused by non-compressive lumbar intervertebral disc herniation.The underlying mechanism involves inhibiting the activation of the ERK and JNK pathways,reducing the expression of pro-inflammatory cytokines and increasing the expression of anti-inflammatory cytokines.
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Objective To investigate the biomechanical and pathological changes in vivo in the taut bands (TB) of biceps femoris in rats after repeated low-frequency electrical stimulation.Methods Twenty-eight Wistar rats were randomly divided into a control group,an electrical intensity-dependent fatigue group,which were subject to electric intensity-dependent fatigue test,and an electrical frequency-dependent fatigue group,which were subject to electrical frequency-dependent fatigue test.After fatigue tests,the taut band of the biceps femoris and the non-taut band of the contralateral biceps femoris were harvested for pathological observation.The maximum contraction force (MCF),electrical intensity-and frequency-dependent fatigue characteristics and any pathological changes in the TBs were assessed and compared to the non-taut band region of the other biceps femoris.Results The MCF at the 15th and 20th stimulation (1.42 ± 0.28 g and 0.93 ± 0.54 g respectively) were significantly lower than that at the 1 st and 5th stimulation of the TBs.High stimulation intensity (HSI) at the 15th and 20th stimulation (3.76 ± 0.71 V and 3.44 ± 0.97 V) were also significantly lower than at the 1st TB stimulation.At the 10th,15th and 20th stimulation of the TBs,MCF and HSI were both significantly lower than in the bands which were not tight.In the frequency-dependent fatigue stimulation tests,the frequency which generated the MCF of the TBs was significantly lower than in the bands which were not tight,while the MCF of the TBs was significantly higher than that of non-TBs.After either intensity or frequency fatigue testing,more severe edema,uneven cytoplasmic death and degeneration of muscle fibers were observed in sections from TBs than from the bands which were not tight.Conclusions Taut muscle bands are significantly less fatigue-resistant than normal muscle fibers.Taut bands may contribute to the fatigue of myofascial pain syndromes.