title: Intervertebral disc reconstitution after chemonucleolysis with chymopapain is dependent on dosage.
abstract: METHODS
  The current report describes a study in beagles in which the effects of intradiscal injection of three doses of chymopapain were evaluated with respect to the reduction of disc width and reconstitution of the nucleus pulposus.
  
  
  OBJECTIVE
  To establish an intradiscal dose of chymopapain that would achieve optimal reduction in disc height followed by maximum reconstitution of the nucleus pulposus.
  
  
  BACKGROUND
  Earlier reports of the efficacy of high and low doses of chymopapain for chemonucleolysis have provided conflicting data, and a scientific basis for an appropriate dose is lacking.
  
  
  METHODS
  Four mature, female beagles were subjected to chemonucleolysis using three doses of chymopapain as Chymodiactin (31, 63 and 125 picokatals/disc) injected into the L2-L3, L1-L2, and L3-L4 discs. Disc widths were monitored radiographically over 32 weeks. Proteoglycans were radiolabeled by intravenous injection with Na2 35SO4 (1 mCi/kg) 24 hours before sacrifice, and their specific activities (disintegrations per minute/mg proteoglycan), hydrodynamic size, and ability to aggregate determined.
  
  
  RESULTS
  Sixty-three picokatals of Chymodiactin produced optimal disc reconstitution after chemonucleolysis. A reduction in disc height of approximately 35% was evident within 1 month and this slowly returned to approximately 90% of the preinjection value after 32 weeks. The nucleus pulposus contained approximately 75% of the proteoglycan content of control tissues, and most of these formed aggregates with hyaluronan. Disc collagen levels remained relatively unaffected by treatment.
  
  
  CONCLUSIONS
  This study demonstrates that an effective reduction in disc width compatible with later reconstitution of the nucleus pulposus can be achieved experimentally with an appropriate dose of chymopapain. These data clearly indicate that an optimal dose of chymopapain for chemonucleolysis in humans needs to be established.
authors.affiliation: Raymond Purves Bone and Joint Research Laboratories, The Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Melrose
authors.forename: T K
authors.initials: TK
authors.lastname: Taylor
authors.forename: P
authors.initials: P
authors.lastname: Ghosh
authors.forename: C
authors.initials: C
authors.lastname: Holbert
authors.forename: C
authors.initials: C
authors.lastname: Macpherson
authors.forename: C R
authors.initials: CR
authors.lastname: Bellenger
mesh_terms: D000818:Animals; D002917:Chymopapain / Q000008:administration & dosage / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007404:Intervertebral Disc Chemolysis; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D011509:Proteoglycans; D003094:Collagen; D002917:Chymopapain