Objective To investigate the role of CCL2 in pain facilitation and spinal mechanisms in the rat model of bone cancer pain.Methods The bone cancer pain model was developed by inoculating.Walker 256 mammary gland carcinoma cells into the rat tibia medullary cavity.SD female rats were divided into 5 groups randomly ( n =8):sham group( group Ⅰ),sham + CCL2 antibody group( group Ⅱ),BCP group( group Ⅲ),BCP +control lgG group ( group Ⅳ),BCP + CCL2 antibody group ( group Ⅴ ).VonFrey threshold was measured one day before operation and 1 st,3 rd,5th,7th,10th,14th,21 st after operation.CCL2 antibody or control lgG was injected intrathecally from 10th to 12th day.The expression of the spinal Iba-1 ( microglial marker) in rat lumbar4-5 was detected by immunohistochemistry assay.Results From the 10th to 21st day after operation,the PMWT of group Ⅲ rats were ( 1.78 ±0.38)g,( 1.70 ±0.17)g,( 1.35 ±0.07 )g;group Ⅳ rats were (2.99 ±0.67)g,(2.52 ±0.75)g,(1.13±0.07)g ; and group Ⅴ rats were (5.88±0.66)g,(7.81 ±0.75)g,(6.19±0.53)g.Compared with group Ⅲ,the PMWT of group Ⅴ was remarkly higher (P＜0.01) ; group Ⅳ had no obvious statistical significance (P＞0.05).At the 14th day after operation,the MOD of group Ⅲ,Ⅳ and Ⅴ rats were (151.3 ±10.8 ),( 149.2 ± 10.6),(74.5 ± 5.0),Compared with group Ⅲ,the MOD of group Ⅴ was significantly increased (P＜0.01 ),group Ⅳ had no obvious statistical significance (P ＞ 0.05 ).Conclusion Intrathecal injection of CCL2 antibody can remarkly attenuate established pain facilitation of tibial bone cancer pain rats,and significantly suppress the expression of Iba-1.It suggests that CCL2 is involved in the bone cancer pain via activation of spinal microglia.

Objective To investigate the role of chemokine ligand 2 (CCL2) in the spinal cord expression in a rat model of tibia bone cancer pain.Methods Eighty-four female SD rats weighing 160-180 g were randomly divided into 3 groups ( n =28):control group (group C),sham operation group (group S) and tibia bone cancer pain group (group P).Tibia bone cancer pain was induced by intra-tibial inoculation of Walker-256 breast cancer cells.Paw withdral threshold to mechanical stimulation (MWT) was measured with von Frey filaments at 1 d before and at 1,3,7,10,14 and 21 d after inoculation.Six rats in each group were sacrificed after the measurement of MWT at 1 d before inoculation and at 7,14 and 21 d after inoculation.Lumbar 4-6 segments of the spinal cord were removed for determination of the expression of CCL2 by ELISA.The coexpression of CCL2 with Iba-1 (a specific marker of microglia),GFAP(a specific marker of astrocyte) and NeuN (a specific marker of neuron) was determined by double immunofluorescence assay after the measurement of MWT at 14 d after inoculation in group P.Results Compared with groups C and S,MWT was significantly decreased from 7 d to 21 d after inoculation,the expressive of CCI-2 in the spinal cord up-regulated at 7,14 and 21 d after inoculation in group P ( P ＜ 0.05).CCL2 was expressed in the microglia and astrocyte but not in neuron in the spinal cord dorsal horn in a rat model of tibia bone cancer pain.Conclusion Release of CCL2 from microglia and astrocytes in the spinal cord was involved in mechanical hyperalgesia in a rat model of tibia bone cancer pain.

Objective To evaluate the effects of intrathecal methotrexate on the activation of microglia in spinal cord in a rat model of tibial cancer pain (TCP).Methods Thirty female Sprague-Dawley rats,aged 5-7 weeks,weighing 150-180 g,were randomly divided into 3 groups (n =10 each):sham operation + artificial cerebrospinal fluid (group SA),TCP + artificial cerebrospinal fluid (group CA),and TCP + methotrexate (group CM).TCP was induced by injecting Walker-256 cancer cells into the medullary cavity of tibia.Artificial cerebrospinal fluid or methotrexate 100μg (15μl) was injected intrathecally over 10 min on 7th day after TCP.Mechanical pain threshold (MPT) was measured before TCP,at 1,3,5 and 7 days after TCP and 2,4,8 and 24 h after administration (T0-8).The rats were sacrificed after measurement of the pain threshold at T8 and the spinal cord was isolated for detection of the activation of microglia (by immunofluorescence) and content of tumor necrosis factor-α (TNF-α) and IL-1β (by ELISA).Results Compared with group SA,MPT was significantly decreased,and the number of activated microglia cells in the spinal cord was increased,and the contents of TNF-α and IL-1β were increased in groups CA and CM (P ＜ 0.05).Compared with group CA,MPT was significantly increased,and the number of activated microglia cells in the spinal cord was decreased,and the contents of TNF-α and IL-1β were decreased in group CM (P ＜ 0.05).Conclusion The mechanism by which intrathecal methotrexate reduces TCP in rats is related to inhibition of the activation of microglia and reduction of the secretion of proinflammatory cytokines TNF-α and IL-1β in the spinal cord.

Objective To compare the efficacy of percutaneous transforaminal endoscopic discectomy with minimally invasive ozone therapy in the treatment of lumbar disc herniation combined with lumbar canal stenosis. Methods The clinical data of 90 patients with lumbar disc herniation combined with lumbar canal stenosis from May 2015 to May 2017 were analyzed retrospectively. The patients were divided into 2 groups according to the method of operation, control group (45 patients received minimally invasive ozone therapy), and observation group (45 patients received percutaneous transforaminal endoscopic discectomy). The basic surgical conditions, visual analog score (VAS), Oswestry dysfunction index (ODI), Japanese Orthopedic Association (JOA) score and efficacy were compared between 2 groups.Results The operation time in observation group was significantly longer than that in control group:(81.93 ± 17.02)min vs.(42.41 ± 15.69)min,postoperative hospitalization time was significantly shorter than that in control group: (1.27 ± 1.05) d vs. (4.29 ± 2.03) d, and there were statistical differences(t=-9.571 and 3.742,P<0.01).The VAS 1 week and 1 month after operation in observation group was significantly lower than that in control group:(4.29 ± 1.39)scores vs.(5.91 ± 1.51) scores and(2.53 ± 0.69)scores vs.(3.25 ± 0.94)scores,and there was statistical difference(P<0.01 or<0.05).The ODI and JOA score 3 months after operation in observation group were significantly better than those in control group: (13.24 ± 5.86) scores vs. (27.83 ± 8.91) scores and (24.24 ± 3.09) scores vs. (20.95 ± 6.25) scores, and there were statistical differences (P<0.01). The eligible rate in observation group was significantly higher than that in control group: 86.67%(39/45)vs.68.89%(31/45),and there was statistical difference(χ2=4.114,P<0.05).Conclusions Percutaneous transforaminal endoscopic discectomy compared with minimally invasive ozone therapy for lumbar disc herniation combined with lumbar canal stenosis is more effective,with shorter postoperative length of stay,more obvious pain relief and more quick lumbar function recovery after operation.