Effects of vitamin D administration on nociception and spinal cord pro-oxidant and antioxidant markers in a rat model of neuropathic pain

Reactive oxygen species (ROS) are involved in neuropathic pain, a complicated condition after nerve tissue lesion. Vitamin D appears to improve symptoms of pain and exhibits antioxidant properties. We investigated the effects of oral administration of vitamin D3, the active form of vitamin D, on nociception, the sciatic functional index (SFI), and spinal cord pro-oxidant and antioxidant markers in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. Vitamin D3 (500 IU/kg per day) attenuated the CCI-induced decrease in mechanical withdrawal threshold and thermal withdrawal latency (indicators of antinociception) and SFI. The vitamin prevented increased lipid hydroperoxide levels in injured sciatic nerve without change to total antioxidant capacity (TAC). Vitamin D3 prevented increased lipid hydroperoxide, superoxide anion generation (SAG), and hydrogen peroxide (H2O2) levels in the spinal cord, which were found in rats without treatment at 7 and 28 days post-CCI. A significant negative correlation was found between mechanical threshold and SAG and between mechanical threshold and H2O2 at day 7. Vitamin D3 also prevented decreased spinal cord total thiols content. There was an increase in TAC in the spinal cord of vitamin-treated CCI rats, compared to CCI rats without treatment only at 28 days. No significant changes were found in body weight and blood parameters of hepatic and renal function. These findings demonstrated, for first time, that vitamin D modulated pro-oxidant and antioxidant markers in the spinal cord. Since antinociception occurred in parallel with oxidative changes in the spinal cord, the oxidative changes may have contributed to vitamin D-induced antinociception.

Abirritation of Discogenic Pain Model in SD Rats by Paravertebral Ozone Injection / 中山大学学报(医学科学版)

@#【Objective】To investigate the analgesic and degenerated regularity of paravertebral ozone injection in the discogenic pain model of SD rats ，and to reveal the mechanism of analgesic effect of ozone preliminarily.【Methods】 Male SD rats（n = 65）were randomly divided into control group（n = 15），model group（n = 25）and ozone group（n = 25）. The L5- 6 intervertebral discs of SD rats in model group and ozone group were punctured to establish discogenic pain models. Ozone was injected paravertebrally in ozone group rats on the 22nd day after modeling. The rats in control group were normal. A quantitative allodynia assessment technique and MRI were used to detect the 50% mechanical withdrawal threshold（50%MWT）and Pfirrmann grade of L5-6 intervertebral discs at different time intervals. The expression of tumor necrosis factor-α（TNF- α）and calcitonin gene-related peptide（CGRP）in left dorsal root ganglion and sciatic nerve were detected by western blot.【Results】The 50% MWT of both hind paws were different from each other in three groups at each time after the 22nd day after modeling（P < 0.05）. In the ozone group，the 50% MWT rose on the 22nd day after modeling（left 7.6±6.8，right 3.6±1.0，P < 0.05 vs pre-ozone injection），and reached the peak on the 24th day after modeling（left 10.6±8.2，right 7.9±6.7，P < 0.05 vs pre-ozone injection），and maintained this level until the 56th day after molding. In the ozone group，the L5-6 intervertebral disc degeneration was apparently visible compared with model group（P < 0.05）. The expression of TNF- α and CGRP in dorsal root ganglion and sciatic nerve were different from each other in three groups（model>ozone>control，P < 0.05）.【conclusions】Paravertebral ozone injection can alleviate the pain of discogenic pain model rats，but aggravates the degeneration of the lumbar disc. Paravertebral ozone injection can reduce the expression of TNF-α and CGRP in the sciatic nerve and dorsal root ganglia of discogenic pain model rats.

Effect of butorphanol and sufentanil with epidural injections on neurobehavior function in bone cancer pain model rats / 中华行为医学与脑科学杂志

Objective To observe the effect of different doses of butorphanol and sufentanil repeatedly epidural injected on the neurobehavior function in bone cancer model rats.Methods A PE-530 catheter was inserted into the epidural space of all male Sprague-Dawley rats(not mated,weighting 150-180 g) at L1-2 level.Three days after operation,64 rats without any motor dysfunction were randomly divided into eight groups (n=8):sham operated group (group C),normal saline with bone cancer pain group (group N),butorphanol groups(group B 1,B2,B3)and sufentanil groups (group S1,S2,S3).Bone cancer pain model was constructed in group N,B and S when rats in group C were sham operated.Rats in group C and N were epidurally injected NS 30μl each,and rats in group B1,B2 and B3 were respectively epidurally injected butorphanol 25,50,100 μg (all diluted to 30 μl with NS),when rats in group S1,S2 and S3 were respectively cpidurally injected sufentanil 1,2,4 μg (all diluted to 30 μl with NS) on time per day for 10-14 days after modeling.The neurobehavior paw withdrawal threshold (MWT) of the left hind claw was recorded to observe the changes in pain behavior.The neurobehavior function of rats were recorded by BBB (BASSO,BEATTIE and BRESNAHAN) score and the inclined plane test.Results Compared with group C((67.65±9.29) g),the MWT of the model groups obviously decreased before the first time of injection (N (15.23± 2.46) g,B 1 (16.14±2.28) g,B2(15.42±3.22) g,B3(14.35±2.32) g,S1 (15.37±2.11)g,S2(15.22±2.93) g,S3(16.25± 2.36) g) (all P＜0.05)).Compared with group N((16.13±2.37) g),the MWT of group B2,B3 and S3 increased obviously after the first time of injection ((35.12±5.16) g,(35.63± 1.53) g and (34.24±5.93) g) (P＜ 0.05).At the first day of injection,there was no significant difference in the BBB scores and the inclined plane test between the model groups (P＞0.05).At 6 h after the forth injection the inclined plane test and the BBB scores of group B3 were obviously decreased compared with group N ((34.72 ± 4.56) ° and (10.64 ± 1.82) points to (43.15±4.67)° and (14.05±1.78) points (P＜0.05)).Conclusion The results provide evidence that repeatedly epidural injection of butorphanol 50 μg or 100 μg or sufentanil 4 μg can reduce the pain of the rats with bone cancer pain.But repeated epidural injection of butorphanol 100 μg can injure the neurological function.

Gabapentin reduces mechanical allodynia in a rat model of tibial bone cancer pain / 中华行为医学与脑科学杂志

ObjectiveTo explore the effects of gabapentin on mechanical allodynia in rats with tibial bone cancer pain (BCP).MethodsForty-two female SD rats were randomized into 7 groups ( n=6):naive group (group N ),sham operation + NS control group (group SN),sham operation + GBP200mg/( kg · d) group (group SG200),BCP + NS control group (group BN),BCP + GBP50mg/( kg · d) group ( group BGS0),BCP +GBP100mg/(kg · d) group (group BG100),and BCP + GBP200mg/(kg · d) group (group BG200).The rats in group N,SN and BN received 5 ml normal saline and the rats in group SG200,BG50,BG100 and BG200 received 200,50,100 and 200 mg/( kg · d) dose of GBP via feeding from day 7 to 13 after operation,respectively.Mechanical withdrawal threshold(MWT) of the right paw and behavioral assays for ambulatory pain were measured just before operation and on days 1,3,5,7,8,10,12 and 14 after operation.ResultsMWT( (3.78 ± 0.38)g) in rats with BCP decreased and behavioral assays for ambulatory pain (0.76 ± 0.44) increased on day 7 after operation,as compared with those in group N ( ( 14.50 ± 1.38 ) g,(0.00 ± 0.00 ) ) and group sham ( ( 10.21 ± 0.88 ) g,( 0.00 ±0.00) ) (P ＜ 0.05 ).There was no apparent praxiological difference between group SN and group SG200 in a week of continuous application of gabapentin(P＞ 0.05 ).Compared with those in group BN,there was no change on MWT in group BG50 (P ＞ 0.05 ),and however,behavioral assays for ambulatory pain decreased (P ＜ 0.05 ).MWT in group BG100( (5.35 ±0.85)g) and BG200( (5.71 ±0.72) g) increased in day 10 after operation,as compared with those in group BN ( ( 2.61 ± 0.40) g) and group BG50 ( ( 3.28 ± 1.15 ) g) (P ＜ 0.05 ),and the difference was still statistically significant until day 14 (P ＜ 0.05 ).Behavioral assays for ambulatory pain in group BG100 and BG200 decreased from day 8 after operation,as compared with those in group BN and group BG50 (P ＜ 0.05 ).ConclusionGabapentin,in medium to large dosage,can inhibit pain reaction of rats with bone cancer pain.Nevertheless,with the development of cancer,the effect of gabapentin decreases.