The Journal of Bone and Joint Surgery, Vol 65, Issue 9 1220-1231, Copyright © 1983 by Journal of Bone and Joint Surgery, Inc
Chymopapain, chemonucleolysis, and nucleus pulposus regeneration
DS Bradford, KM Cooper and TR Oegema
In the adult mongrel dog, in vivo injection of chymopapain into the
intervertebral disc resulted in disc-space narrowing at two weeks, with a
complete loss of proteoglycan (as indicated by safranin-O staining) from
the nucleus pulposus, the cartilaginous end-plates, and the annulus
fibrosus. As demonstrated by [35S]sulphate-labeling and proteoglycan
isolation, the nucleus pulposus retained the ability to synthesize
proteoglycans, but these were degraded by endogenous proteolytic activity.
Three months after chymopapain treatment the intervertebral disc showed an
increase in height. There was a return of intense safranin-O staining in
the annulus and the cartilaginous end-plates, and very prominently in the
nucleus. The proteoglycans that were present were recovered as aggregates,
with the proteoglycan monomer being slightly larger than in the controls.
Six months after chymopapain treatment the intervertebral disc had
increased further in height, and normal histology had been restored. The
chemical composition and physical properties of the proteoglycans that were
isolated from the nucleus pulposus were essentially the same as those from
the controls. These observations suggest that the nucleus can regenerate
following the injection of chymopapain. Clinical Relevance: Our
observations demonstrate that chymopapain has a profound but reversible
effect on the intervertebral disc. The radiographic narrowing of the
intervertebral disc following chymopapain injection correlates with the
loss of proteoglycan content and structure. The restoration of normal disc
height following chymopapain injection is explained by reconstitution of
the intervertebral disc with normal proteoglycans. In experimental animals,
chemonucleolysis with chymopapain appears to be less likely than surgical
excision to permanently alter the biochemistry of the nucleus pulposus.