The effect of epidural injections with different dose of butorphanol or sufentanil on the rats' spinal cord morphology and serum myelin basic protein in bone cancer pain models

Abstract

Objective To observe the effect of epidural injection with different dose of butorphanol or sufentanil on the rats' spinal cord morphology and serum myelin basic protein(MBP) in bone cancer pain models. 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-L2 level. Three days after operation, 64 rats without any motor dysfunction were randomly divided into eight groups(n=8): sham operation group (group C), normal saline group (group N), butorphanol groups(group B1, 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 30 μl 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 epidurally injected sufentanil 1, 2, 4 μg (all diluted to 30 μl with NS) in time per day 10-14 days after modeling. These serum MBP of rats were measured before injection (T0), 6 h(T1), 24 h(T2) and 72 h (T3) after the last injection by ELISA examination. At T3, took out the lumbar enlargement of the spinal cord, and detected the H-E, Bcl-2, Bax, tunel and electron microscopy. Results The content of serum MBP did not show any significant difference between groups(P>0.05). Compared with group C, N, B1, B2, S1, S2 and S3, the number of nissl body in group B3 decreased[(37.6±3.7), (39.3±3.6), (36.1±3.1), (37.3±2.9), (38.4±2.9), (35.7±3.3) and(35.3±3.2) to (22.3±2.7)(P<0.05)], the number of cells with Bcl-2 in group B3 decreased obviously[(9.8±1.5), (10.1±1.3), (12.5±1.7), (13.1±2.2), (11.5±1.8), (12.6±1.9), (13.3±2.3) to (29.8±5.6)(P<0.05)], the expression of the Bax in group B3 increased obviously[(8.6±2.2), (9.3±1.6), (10.1±1.7), (9.9±1.9), (8.4±2.1), (9.7±1.3), (11.3±1.8) to (31.8±5.3)(P<0.05)], the number of the apoptosis neurons in group B3 increased obviously[(6.6±2.3), (6.3±2.6), (7.1±1.7), (7.9±1.3), (8.4±1.1), (9.7±1.3), (8.3±1.7) to(15.2± 2.3) (P<0.05)]. The structure of myelin in group B3 was destroyed but not demyelinated in the electron microscope. Conclusions Repeated epidural injection of butorphanol 50 μg or sufentanil 4 μg have no effect on spinal cord cells and subcellular structures of rats and on the apoptosis of spinal cord in bone cancer pain models, while repeated epidural injection of butorphanol 100 μg could decrease the content of nissl bodies but increase the apoptosis in spinal cord cells and destroy the structure of myelin. Myelin basic protein has no change in all groups. Key words: Butorphanol; Sufentanil; Bone cancer pain; Epidural injection; Spinal cord; Cell structure; Myelin basic protein