LETTER TO THE EDITOR

CHYMOPAPAIN: A SHOT FROM THE PAST

Chemonucleolysis with chymopapain was initiallydescribed by Smith et al. in 1964 and was proposed as amanagement option for contained disc herniationswithout sequestration or extrusion.1 The proteolyticenzyme that was derived from papaya was thought tocatalyze hydrolysis of proteins in the nucleus pulposus,2

which decreases the affinity for water molecules byproteoglycans.

A number of randomized double-blind controlledtrials have demonstrated that chymopapin injections aremore effective than placebo.3–6 A recent meta-analysissuggested that chemonucleolysis with chymopapain hadconsistently worse results when compared with surgical

discectomy.7 A 5-year follow-up of 100 patients thathad undergone chemonucleolysis with chymopapainconcluded that there was no disc deterioration or otheradverse reactions;8 however, studies with longerfollow-up have not been described. A thorough reviewof 42 clinical trials suggested that overall, chymopapainchemonucleolysis is not as effective as discectomy, butseems to be better than placebo. The authors concludethat many chymopapain chemonucleolysis patients goon to require discectomy, and therefore, the overalleffect of the intervention is not significant (Figure 1).6

Chymopapain chemonucleolysis became the topic ofcontroversy after a number of patients were reported tohave developed anaphylaxis and death after administra-tion; its use was banned for a short time by the Food and

(a) (b)

Figure 1. Sagittal T1-weighted image(a) and T2-weighted image (b) in apatient that had undergone chymopa-pin chemonucleolysis at L3–4 andL4–5, 27 years prior to visit. Dispropor-tionate degenerative disc disease isidentified at L3–4 and L4–5.

© 2008 World Institute of Pain, 1530-7085/08/$15.00Pain Practice, Volume 8, Issue 4, 2008 331–332

Drug Administration. Reinjection of chymopapain con-tinues to be prohibited in the United States for fear ofsensitization and anaphylaxis. Review of the literaturesuggests that chymopapain chemonucleolysis achievesexactly what it was meant to do, ie, promotes hydrolysisand disc desiccation. However, a larger question seemsto be—in an era in which our patients live longerand develop degenerative disc disease and all of itssequelae, is induced desiccation by chemonucleolysis anappropriate goal?

Raj Mitra, MD; Matthew Wedemeyer, M;Ivan Cheng, MD

Division of Physical Medicine and RehabilitationDepartment of Orthopaedic Surgery

Stanford University, School of MedicineStanford, CA 94305, USA

E-mail: rmitra@stanford.edu

ACKNOWLEDGEMENTS

To Miss Jackie Guingona, for her assistance in thepreparation of this letter.

REFERENCES

1. Smith L. Enzyme dissolution of nucleus pulposus inhumans. JAMA. 1964;187:137–140.

2. Javid MJ, Nordby EJ. Lumbar chymopapain nucle-olysis. Neurosurg Clin N Am. 1996;7:17–27.

3. Martins AN, Ramirez A, Johnston J, et al. Double-blind evaluation of chemonucleolysis for herniated lumbardiscs. Late results. J Neurosurg. 1978;49:816–827.

4. Fraser RD. Chymopapain for the treatment of inter-vertebral disc herniation. A preliminary report of a double-blind study. Spine. 1982;7:608–612.

5. Javid MJ, Nordby EJ, Ford LT, et al. Safety andefficacy of chymopapain (Chymodiactin) in herniated nucleuspulposus with sciatica. JAMA. 1983;249:2489–2494.

6. Feldman J, Menkes CJ, Pallardy G, et al. Double-blind study of the treatment of disc lumbosciatica by chemo-nucleolysis [Etude en double-aveugle du traitement de lalombosciatique discale par chimionucleolyse]. Rev Rhum MalOsteoartic. 1986;53:147–152.

7. Gibson J, Waddell G. Surgical interventions forlumbar disc prolapse. Cochrane Database Syst Rev. 2007;2:CD001350.

8. Wittenberg RH, Oppel S, Rubenthaler FA, et al.Five-year results from chemonucleolysis with chymopapain orcollagenase: a prospective randomized study. Spine. 2001;26:1835–1841.

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