Effects of collagenase and chymopapain on spinal nerves and intervertebral discs of cynomolgus monkeys.
In order to test the safety and efficacy of Nucleolysin, a collagenase for intradiscal chemotherapy, laminectomies were performed on the L2-3 intervertebral discs of four groups of three young adult Cynomolgus monkeys. One primate from each group was injected with half the recommended human dose of Nucleolysin, chymopapain, or the same volume of sterile water. The remaining half of the human dose of each drug or equal volume of sterile water was equally divided and placed upon the right L-3 and L-4 nerve roots at their vertebral foramina. The right L-4 nerve root was first compressed for 10 seconds with an aneurysm clip. These procedures were done to simulate inadvertent contact of enzyme with spinal nerves in patients undergoing chemonucleolysis. After 4 weeks of observation, the 12 primates were humanely killed and examined post mortem. The effects of both enzymes were limited to those tissues with which they came in direct contact. Complete digestion of the nucleus pulposus of all enzyme-injected intervertebral discs was observed. Variable portions of the anulus fibrosus (from 2.3% to 57.4%) were also dissolved. Direct contact of Nucleolysin with lumbar nerve roots caused minor perineural reaction and no more intraneural changes than seen in sterile water controls. Chymopapain induced mild to severe perineural skeletal muscle necrosis and fibrosis with perineural arterial lesions as well as a degenerative neuropathy which was more marked in the traumatized nerve. The results of this study suggest that Nucleolysin and chymopapain are approximately equally effective on intervertebral discs, and that Nucleolysin is less injurious to spinal nerve roots and perineural tissue at the doses used.
D000818:Animals; D002917:Chymopapain / Q000627:therapeutic use*; D007403:Intervertebral Disc / Q000187:drug effects / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D003012:Microbial Collagenase / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013122:Spinal Diseases / Q000188:drug therapy / Q000473:pathology; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000473:pathology
D002917:Chymopapain; D003012:Microbial Collagenase