Objective: To evaluate the effects of intrathecal administration p38 beta antisense oligonucleotide on the development of bone cancer pain rats. Methods: Forty female SD rats weighing 180 similar to 220 g were randomly divided into 4 groups (n = 10 each): Group A (control group): intra-tibial injection of 3 mu l Hank's solution; group B (model group): intra-tibial injection of 3 mu l MADB-106 mammary gland carcinoma cells of rats (4.8 x 10(3)/mu l); group C (p38 beta-SODN 20 mu g); group D (p38 beta-ASODN 20 mu g). The model procedures in group C and D were same to those in the group B. From the 14th day after operation, p38 beta-SODN 20 mu g and p38 beta-ASODN 20 mu g were respectively intrathecally administrated in group C and D once daily for 6 days whereas normal saline was for group A and B. Mechanical withdrawal threshold and radiant heat threshold of rat hind paws were measured before operation and every other day until 22 d of post-operation. The lumbar 4-6 spinal cord was removed on the 22nd day. The expression of spinal p38 beta protein was determined by Western blot. Results: No significant differences in mechanical withdrawal threshold and radiant heat threshold were found at all time points in control group. During the first 6 days after operation there were obvious differences in radiant heat stimulus between control group between the other groups (P < 0.05); During 14-22 days after operation, mechanical pain threshold and radiant heat threshold between p38 beta-SODN group and Model group were significantly changed compared with that in control group (P < 0.05). However, the differences were not remarkable between control group and p38 beta-ASODN group (P > 0.05). The expression of p38 beta protein in lumbar spinal cord was significantly higher between p38 beta-SODN group and Model group than that in control group (P < 0.05). There was no significant difference in p38 beta protein expression between p38 beta-ASODN group and control group (P > 0.05). Conclusions: Hyperalgesia induced by bone cancer can be inhibited by intrathecal administration of p38 beta antisense oligonucleotide, which is achieved by reducing expression of p38 beta protein.