J. Melrose et al., INTERVERTEBRAL DISC RECONSTITUTION AFTER CHEMONUCLEOLYSIS WITH CHYMOPAPAIN IS DEPENDENT ON DOSAGE - AN EXPERIMENTAL-STUDY IN BEAGLE DOGS, Spine (Philadelphia, Pa. 1976), 21(1), 1996, pp. 9-17
Study Design. The current report describes a study in beagles in which
the effects of intradiscal injection of three doses of chymopapain we
re evaluated with respect to the reduction of disc width and reconstit
ution of the nucleus pulposus. Objectives. To establish an intradiscal
dose of chymopapain that would achieve optimal reduction in disc heig
ht followed by maximum reconstitution of the nucleus pulposus. Summary
of Background Data. Earlier reports of the efficacy of high and low d
oses of chymopapain for chemonucleolysis have provided conflicting dat
a, and a scientific basis for an appropriate dose is lacking. Methods.
Four mature, female beagles were subjected to chemonucleolysis using
three doses of chympopapain as Chymodiactin (31, 63 and 125 picokatals
/disc) injected into the L2-C3, L1-L2, and L3-L4 discs. Disc widths we
re monitored radiographically over 32 weeks. Proteoglycans were radiol
abeled by intravenous injection with (Na2SO4)-S-35 (1 mCi/kg) 24 hours
before sacrifice, and their specific activities (disintegrations per
minute/mg proteoglycan), hydrodynamic size, and ability to aggregate d
etermined. Results. Sixty-three picokatals of Chymodiactin produced op
timal 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 week
s. The nucleus pulposus contained approximately 75% of the proteoglyca
n content of control tissues, and most of these formed aggregates with
hyaluronan. Disc collagen levels remained relatively unaffected by tr
eatment. Conclusions. This study demonstrates that an effective reduct
ion in disc width compatible with later reconstitution pulposus can be
achieved experimentally with an appropriate dose of chymopain. These
data clearly indicate that an optimal dose of chymopapain for chemonuc
leolysis in humans needs to be established.