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PubMed · 6378565

Chymopapain.

T R Einarson·J L Bootman·G H Smith
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Abstract

Chymopapain is a proteolytic enzyme injected intradiscally for the treatment of herniated lumbar discs. The average success rate is 73 percent for elimination of backache and sciatica. Side effects occur in three percent of patients, the most serious being anaphylaxis in about one percent. A majority of patients experience severe back pain or spasms during the first 24-48 hours after treatment. This treatment modality consumes fewer hospital days and produces a quicker return to work than does surgery. It does not affect subsequent surgical procedures adversely. Chymopapain chemonucleolysis is safe and effective when administered by experienced physicians and when adequate precautions are taken. It can be considered the last step before surgery in the conservative management of herniated lumbar discs.

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ChymopapainDrug InteractionsDrug StabilityDrug StorageEndopeptidasesHumansIntervertebral Disc DisplacementLumbar VertebraeJournal ArticleReview

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T R Einarson, J L Bootman, G H Smith. Chymopapain.. https://doi.org/10.1177/106002808401800702

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PubMed1999

Do human lumbar discs reconstitute after chemonucleolysis? A 7-year follow-up study.

STUDY DESIGN: A retrospective, longitudinal study of 51 patients, covering a mean follow-up period of 81 months. OBJECTIVE: To observe the long-term temporal course of the height of human lumbar discs after chemonucleolysis. To document whether human lumbar discs reconstitute, thus characterizing the healing potential of central disc tissue. SUMMARY OF BACKGROUND DATA: Although reconstitution of disc height within some months of chemonucleolysis has been observed in animal experiments, human lumbar discs have shown no tendency to regain their initial height within 1 year of treatment. To date, there has been no report on longer follow-up periods. The different reactions of animal and human discs may be dose-related or related to differences in tissue properties, physiologic environment or in vivo loading conditions. METHODS: Using a new protocol, the heights of lumbar discs were measured from sets of lateral radiographic views of 51 patients subject to chemonucleolysis by treatment with chymopapain (doses of 4000 or 3000 picokatals [pkat]). The sets comprised a view taken before treatment, a view taken (on average) 4 months after treatment, and a view taken (on average) 81 months after treatment. In the majority of patients, untreated discs adjacent to discs treated with chemonucleolysis served as control discs. RESULTS: Shortly after injection of chymopapain, all treated discs decreased in height. The height decrease of treated discs amounted to 15.8% on average. In the subcohort treated with 4000 pkat, the loss did not reverse during the entire follow-up period; in the subcohort treated with 3000 pkat a small fraction of the lost height was regained. Untreated neighboring control discs showed a minor (3.4%) decrease in height. CONCLUSIONS: Human lumbar discs do not reconstitute after chemonucleolysis. Because the long-term temporal course of disc height in patients is in disagreement with observations from animal experiments, caution is suggested when generalizing results from animal studies to humans.

Chymopapain↗
PubMed1998

pH dependence of the activation parameters for chymopapain unfolding: influence of ion pairs on the kinetic stability of proteins.

We studied the irreversible thermal denaturation of chymopapain, a papain-related cysteine proteinase. It was found that this process follows simple first-order kinetics under all conditions tested. Rate constants determined by monitoring ellipticity changes at 220 or 279 nm are essentially identical, indicating that denaturation involves global unfolding of the protein. Enthalpies (DeltaH(double dagger)) and entropies (DeltaS(double dagger)) of activation for unfolding were determined at various pH values from the temperature dependence of the rate constant. In the pH range 1.1-3.0, a large variation of both DeltaH(double dagger) and DeltaS(double dagger) was observed. For the few proteins studied so far (lysozyme, trypsin, barnase) it is known that activation parameters for unfolding vary little with pH. It is proposed that this contrasting behavior of chymopapain originates from the numerous ion pairs - especially those with low solvent accessibilities - present in its molecular structure. In contrast, fewer, more exposed ion pairs are present in the other proteins mentioned above. Our results were analyzed in terms of differences in the protonation behavior of carboxylic groups between the transition (TS) and native (N) states of the protein. For this purpose, a model of independently titrating sites was assumed, which explained reasonably well the pH dependence of activation parameters, as well as the protonation properties of native chymopapain. According to these calculations, pK values of carboxyls in TS are shifted 0.6-0.9 units upwards with respect to those in N. In addition, some groups in TS appear to be protonated with unusually large enthalpy changes.

Chymopapain↗
PubMed1998

[Lumbar disk prolapses and radiological spinal intervention. What do the randomized controlled trials say?].

We searched the Medline database and examined 11 randomized controlled trials to evaluate the efficacy of treating lumbar herniated discs by injection with chymopapain or by automated percutaneous discectomy. Our findings show that chemonucleolysis with chymopapain is a documented treatment which is better than placebo, but consistently inferior to surgical discectomy. The two randomized controlled trials to evaluate automated percutaneous discectomy fail to show efficacy that is any better than would be expected from a placebo response. We conclude that surgical discectomy is the best treatment option for a herniated disc when conservative efforts have failed.

Chymopapain↗