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Chymopapain A. Purification and investigation by covalent chromatography and characterization by two-protonic-state reactivity-probe kinetics, steady-state kinetics and resonance Raman spectroscopy of some dithioacyl derivatives.

Chymopapain A was isolated from the dried latex of papaya (Carica papaya) by ion-exchange chromatography followed by covalent chromatography by thiol-disulphide interchange. The latter procedure was used to produce fully active enzyme containing one essential thiol group per molecule of protein, to establish that the chymopapain A molecule contains, in addition, one non-essential thiol group per molecule and to recalculate the literature value of epsilon 280 for the enzyme as 36 000 M-1 X cm -1. The Michaelis parameters for the hydrolysis of L-benzoylarginine p-nitroanilide and of benzyloxy-carbonyl-lysine nitrophenyl ester at 25 degrees C, and I 0.1 at several pH values catalysed by chymopapain A, papaya proteinase omega, papain (EC 3.4.22.2) and actinidin (EC 3.4.22.14) were determined. Towards these substrates chymopapain A has kcat./km values similar to those of actinidin and of papaya proteinase omega and significantly lower than those of papain or ficin. The environment of the catalytic site of chymopapain A is markedly different from those of other cysteine proteinases studied to date, as evidenced by the pH-dependence of the second-order rate constant (k) for the reaction of the catalytic-site thiol group with 2,2'-dipyridyl disulphide. The striking bell-shaped component that is a characteristic feature of the reactions of S-/ImH+ (thiolate/imidazolium) ion-pair components of many cysteine-proteinase catalytic sites with the 2,2'-dipyridyl disulphide univalent cation is not present in the pH-k profile for the chymopapain A reaction. The result is consistent with the presence of an additional positive charge in, or near, the catalytic site that repels the cationic form of the probe reagent. Resonance Raman spectra were collected at pH values 2.5, 6.0 and 8.0 for each of the following dithioacyl derivatives of chymopapain A: N-benzoylglycine-, N-(Beta-phenylpropionl)glycine- and N-methoxycarbonylphenylalanylglycine-. The main conclusion of the spectral study is that in each case the acyl group binds as a single population known as conformer B in which the glycinic N atom is in close contact with the thiol S atom of the catalytic-site cysteine residue, as is the case also for papain and other cysteine proteinases studied. Thus the abnormal catalytic-site environment of chymopapain A detected by the reactivity-probe studies, which may have consequences for the acylation step of the catalytic act, does not perturb the conformation of the bound acyl group at the acyl-enzyme-intermediate stage of catalysis.

2,2'-Dipyridyl↗

Chymopapain, chemonucleolysis, and nucleus pulposus regeneration.

UNLABELLED: 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.

Animals↗

Proteins: chymopapain and insulin.

We studied clinical and immunologic aspects of the reactions to two newly introduced drugs, chymopapain and human recombinant deoxyribonucleic acid insulin (HI), in patients demonstrating allergies to one of these two drugs. We then used this information to improve our ability to diagnose and prevent chymopapain allergy and to further our understanding of systemic insulin allergy and its management. Of the patients who were sensitive to chymopapain, one had severe anaphylaxis to intradisc injection while the other had rhinitis, asthma, and urticaria with occupational exposure. The latter demonstrated cutaneous reactivity to papain; the former refused skin testing. Both demonstrated immunoglobulin (Ig) E and IgG to chymopapain as measured by enzyme-linked immunosorbent assay. We have prospectively skin tested 61 patients with chymopapain. Sixty-one patients have had negative skin tests and have tolerated the intradisc injection of chymopapain without incident. We are continuing our prospective skin test study in order to identify a population at risk for allergy to chymopapain. Two patients with systemic allergic reactions to animal insulin have at least as much cutaneous reactivity and IgE and IgG antibodies to HI as to porcine insulin. A large local reaction occurred during an attempt to desensitize one of them to HI; the patient was subsequently desensitized without difficulty to porcine insulin, to which she was less skin reactive. We conclude that HI will not eliminate insulin allergy in patients with systemic allergy to animal insulin and that such patients will continue to require the usual therapeutic measures for insulin allergy.

Adult↗

Comparison of tissue reaction with chondroitinase ABC and chymopapain in rabbits as the basis of clinical application in chemonucleolysis.

Although chemonucleolysis with chymopapain is an approved treatment for lumbar intervertebral disk herniation, recent serious complications have raised doubt concerning its safety. It is therefore necessary to search for a safer and more selective agent than chymopapain for chemonucleolysis. Experimental chemonucleolysis with chondroitinase ABC was thus tested and compared with chymopapain. Acute tissue reactions to chondroitinase ABC were investigated and compared with chymopapain. The epidural space, yellow ligament, sciatic nerve, knee joint, and Achilles tendon were examined. Chymopapain damaged nervous and ligamentous tissues as well as cartilaginous tissue. Chondroitinase ABC did not damage nervous and ligamentous tissue. Chondroitinase ABC affected only cartilaginous tissue, and its action was chiefly limited to digestion of the matrix. Chondroitinase ABC has high enzymatic specificity for matrix in vivo. In addition, chondroitinase ABC is less toxic to noncartilaginous tissues than chymopapain. Chondroitinase ABC might be a more suitable and safer enzyme than chymopapain for chemonucleolysis.

Achilles Tendon↗

[Changes in plasma histamine and catecholamines levels after injection of chymopapain in chemonucleolysis].

Because pruritus, erythema and tachycardia are observed in some patients during chemonucleolysis, a prospective study was designed to investigate the plasma levels of histamine and catecholamines occurring after an injection of chymopapain. Thirteen patients (11 men and 2 women), mean age 38 +/- 11 years, were studied. They all had negative prick skin tests, human basophil degranulation tests (HBDT) and radio-absorbent tests (RAST) to chymopapain. The patients were premedicated with 100 mg hydroxyzine and 3 g tranexamic acid. Sedation was carried out using 0.1 mg.kg-1 droperidol and 0.02 mg.kg-1 phenoperidine. The nucleosus pulposus was visualized with 3 ml of contrast medium (lopamiron 300); 2 ml of chymopapain were then injected. Blood samples were obtained at T1 (after the contrast medium, but before the chymopapain), and then 5, 10, 15, 20 and 30 minutes after the chymopapain. The usual haemodynamic parameters were recorded at the same times. Four patients had clinical signs (group I), whereas the other nine (group II) did not. There was an increase in histamine levels in three patients from group 1, as well as in two in group II (up to 33 nmol.l-1). However, mean histamine and catecholamines levels were comparable in both groups at all times, and between times, of sampling. There therefore was no relationship between clinical signs and the release of histamine or catecholamines. The premedication with an antihistamine may have protected the patients, but the signs reported by four patients may also be due to the chymopapain itself.

Adult↗

The effect of diagnostic radiopaque fluids used in discography on chymopapain activity.

It has been thought that intradiscal injection of radioopaque fluids prior to intradiscal chymopapain therapy might have some inhibitory effect on its enzyme activity and, thus, disc nuclear dissolution. This raised the question--what interval should elapse between discography and injection of the chymopapain to avoid this possible effect? The effects of Hypaque (Conray), metrizamide, and Urografin on chymopapain activity were measured. The most suitable substrate was N. Benzoyl-DL-arginine paranitroanilide (BAPNA). The yellow p-nitro aniline liberated (a measure of the enzymic activity of chymopapain) was determined by absorption spectrometry. Controlled series using 1) Hypaque plus substrate plus no enzyme, 2) Hypaque, enzyme, no substrate, and 3) Hypaque plus substrate plus enzyme showed no action. Hypaque (Conray) and Urografin are seen to enhance enzymic action of chymopapain. Metrizamide has slight inhibitory action. Effects of Dimerex were variable. Weak Hypaque increases activity (20%); 100% solution doubles activity. Thus, there is no necessity to delay injection of enzyme after Hypaque, Conray, Urografin, especially as disc radioopacity can persist up to 24 hours. Prior injection of 95% alcohol (as used by Trosier) abolishes chymopapain activity.

Chymopapain↗

Prospective comparative study of intradiscal high-dose and low-dose collagenase versus chymopapain.

The mixed results of two studies on intradiscal therapy with collagenase versus chymopapain are presented. The first study was performed from January 1983 to March 1984 and consisted of 71 patients treated with collagenase injection (600 ABC units) and 93 patients treated with chymopapain injection (4,000 units) into lower lumbar discs. The second study was started in May 1985 and ended December 1985. The results of 41 patients injected with chymopapain and 45 patients injected with collagenase (400 ABC units) are reported. The overall success rate after 3 months was 69%/63% for chymopapain/high-dose collagenase and 73%/71% for chymopapain/low-dose collagenase and 75%/72% after 6 months for chymopapain/high-dose collagenase. Eighteen percent of the chymopapain-treated patients and 21% of the collagenase-treated patients of the first study had to be operated on within 6 months and 12% of chymopapain patients and 29% of collagenase patients within 3 months in the second study. Six of the 134 patients who had chymopapain treatment had slight allergic reactions. Patients who had collagenase treatment had no allergic reactions under the same regimen of systemic prophylactic measures. Patients who had high-dose collagenase injections suffered significantly more from postinjectional pseudoradicular and low-back pain in the first 3 months. In the first study, no permanent neurologic complications occurred. Two patients in the low-dose collagenase group developed cauda equina syndromes in the 2 weeks after injection because of large extruded disc fragments.

Adult↗

Intervertebral disc reconstitution after chemonucleolysis with chymopapain is dependent on dosage.

STUDY DESIGN: 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. OBJECTIVES: To establish an intradiscal dose of chymopapain that would achieve optimal reduction in disc height followed by maximum reconstitution of the nucleus pulposus. SUMMARY OF BACKGROUND DATA: 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.

Animals↗

A comparative study of chemonucleolysis with recombinant human cathepsin L and chymopapain. A radiologic, histologic, and immunohistochemical assessment.

STUDY DESIGN: Investigation of the effects of recombinant human cathepsin L on intervertebral discs and comparison with the effects of chymopapain. OBJECTIVE: To evaluate the effects of cathepsin L on intervertebral discs as an agent for chemonucleolysis. SUMMARY BACKGROUND DATA: Cathepsin L is a typical cysteine proteinase that belongs to the papain superfamily. It plays a major role in intracellular proteolysis and is not believed to induce anaphylactic reactions. METHODS: In vivo: Rabbit intervertebral discs were injected with recombinant human cathepsin L, its buffer solution, and chymopapain. After 1, 4, and 16 weeks the animals were killed, and radiologic and histologic examinations were performed. In vitro: The enzymatic actions of recombinant human cathepsin L and chymopapain on human intervertebral disc proteoglycans were examined immunohistochemically using antiproteoglycan antibodies. RESULTS: In rabbit models, roentgenography showed that disc spaces treated with cathepsin L and chymopapain had become narrower 1 week after injection. Histologically, loss of safranin-O staining was observed in the anulus fibrosus of discs treated with cathepsin L. After 16 weeks, nucleus pulposus had regenerated with chondrocyte-like cells, and the safranin-O staining characteristics of the matrix also had recovered. In an immunohistochemical study, all components of the proteoglycan stained weakly after chymopapain digestion. After cathepsin L digestion, unsulfated chondroitin and core protein staining was weaker, but the chondroitin 6-sulfate staining was unaffected. CONCLUSIONS: Cathepsin L seems to be an effective agent for chemonucleolysis. Its enzymatic action on proteoglycan appears to be different from that of chymopapain.

Adult↗

Spinal flexibility increase after chymopapain injection is dose dependent: a possible alternative to anterior release in scoliosis.

STUDY DESIGN: Experimental animal study. OBJECTIVES: To investigate whether the increase in spinal flexibility after chymopapain injection is dose dependent and determine the "optimal" dosage of chymopapain to increase spinal flexibility in a rabbit model. SUMMARY OF BACKGROUND DATA: Spinal instability after chymopapain injection may result in severe back pain. However, this undesired mechanical effect in treating disc herniation may provide a safe minimally invasive approach for anterior spinal release in scoliosis correction. METHODS: A total of 138 lumbar intervertebral discs from 46 New Zealand white rabbits were randomly injected with chymopapain at 6.25, 12.5, 25, 50, 75, and 100 picokatals (pKats)/0.05 mL/disc. The rabbits were killed 1 week after the injection, and the lateral bending stiffness of the spinal segments without posterior elements was determined. RESULTS: The lateral bending spinal stiffness showed no significant change after injection of 6.25 and 12.5 pKats/0.05 mL/disc but reduced significantly following chymopapain injection of 25, 50, 75, and 100 pKats (all P < 0.05 by post hoc least significant difference tests). While the lateral bending stiffness was lowest at the 100-pKats dose, there were no significant differences between the four higher dosages. CONCLUSION: The reduction in the lateral bending spinal stiffness after chymopapain injection is dose dependent, and an optimal dosage for spinal release existed; doses greater than the optimal dosage did not result in further significant decrease in lateral bending spinal stiffness.

Animals↗

Effect of chymopapain on the meninges studied in an experimental model.

The effect of chymopapain and contrast media in the epidural space on meninges has not been studied conclusively. The authors injected chymopapain into the epidural space of monkeys and measured the degree of arachnoid fibrosis that resulted. Animals were given injections of 1.2 mL of diatrizoate (280 mg iodine per milliliter), chymopapain (100 IU/mL), kaolin (100 mg/mL) (as a positive control), or saline (0.9%) (as a negative control). Three months later the animals were killed; the dural sac was removed intact and was fixed, sectioned, stained, and examined with light microscopy. Kaolin-treated animals developed mild to marked fibrosis of the dura. The saline- and diatrizoate-treated animals developed little or no evidence of fibrosis. One of four chymopapain-treated animals developed degenerative changes in dorsal nerve roots and fibrosis in the adjacent arachnoid. The other chymopapain-treated animals had little or no evidence of fibrosis. The studies suggest that neither diatrizoate nor chymopapain causes arachnoid fibrosis.

Animals↗

Experimental chemonucleolysis with chymopapain in canine intervertebral disks.

The present study describes the radiological and histological changes in the canine intervertebral disk after the experimental injection of chymopapain as the chemical reagent, and determines the appropriate dose of the enzyme for treatment of herniated disks. By radiography, narrowing of the disk space was observed within 2 weeks after the injection of chymopapain, and recovered to 74.1% in the 0.1 mg group, 61.1% in the 1.0 mg group and 71.7% in the 10.0 mg group at 12 weeks. The disk space recovery showed a tendency to delay with aging. Microscopically, proteoglycan positive matrix appeared and the nuclear space was reduced in each disk at 2 weeks after chymopapain injection. The nucleus pulposus contained an irregularly-defined mass consisting of clusters of degenerated notochordal cells surrounded by proliferated chondrocytes and collagen matrix. In each disk at 12 weeks after chymopapain injection, the center of the nucleus pulposus was replaced by fibrocartilage tissue. In the disk into which 10.0 mg chymopapain was injected, the nuclear space filled with dense fibrocartilage tissue without a regenerated matrix component and narrowing of the disk were maintained. It is suggested that canine chemonucleolysis with 10.0 mg of chymopapain reduces the interdiskal pressure. This treatment may therefore relieve the signs and symptoms of herniation of the nucleus pulposus, and may effect chemical disk decompression.

Animals↗

Chymopapain chemonucleolysis versus surgical discectomy in a military population.

From 1983 to 1987, 100 consecutive patients with lumbar herniated nucleus pulposus were treated with either chymopapain chemonucleolysis (51 patients) or surgical discectomy (49 patients). The chymopapain-treated group was followed for an average of 16 months and the surgically treated group was followed for an average of 12 months. All patients had to be candidates for both procedures and were grouped for therapy based on their preference. The groups were similar in military duty status, history, age, gender, duration and character of symptoms, physical findings, and computed tomography/myelogram results. Satisfactory outcomes were achieved in 40 of 51 (78%) chymopapain-treated patients and in 39 of 49 (80%) surgically treated patients. Seventy-eight percent of the chymopapain group and 79% of the surgery group ultimately returned to full military duty. Of the nine initial chymopapain failures, eight were successfully treated with surgical discectomy. There were fewer complications, 4% versus 10%, in the chymopapain group. The authors now consider chemonucleolysis as the final conservative measure prior to surgery, rather than an alternative to surgical discectomy.

Adult↗

Nucleolysis and diskography--an experimental study on interaction of chymopapain and contrast medium.

A test was carried out on 11 young, full sized mongrels to determine whether there is an interaction between chymopapain and the contrast agents iotrolan and iopamidol. A total of 75 intervertebral disks were punctured: nucleolysis alone was performed on 20, diskography with iotrolan and subsequent nucleolysis on 20, and diskography with iopamidol and subsequent nucleolysis on 10. Diskography alone was performed 10 times with iotrolan and 5 times with iopamidol. Aqua dest. was given intradiskally 5 times, and puncture was carried out 5 times without the administration of any substance. Following puncture, x-rays of the lumbar vertebral column were taken laterally: daily for the first 10 days, then weekly. Disk space narrowing typical of nucleolysis with chymopapain was found among the disks that were nucleolyzed only to the same extent as among those that had undergone diskography previously. There was no evidence of narrowing of the other disk spaces which had been punctured but not treated with chymopapain. On some of the dogs, CT and MRI examinations were carried out. The CTs showed a homogenous hypodensity in all of the disks, in which chymopapain had been injected. The MRI revealed a signal loss in all of the nucleolyzed disks. The results of short and long term follow up demonstrate that inhibition of chymopapain by iotrolan or iopamidol is not to be expected and therefore diskography prior to chemonucleolysis can be performed without danger of enzyme inactivation.

Animals↗

Skin testing for chymopapain allergy in chemonucleolysis.

Chemonucleolysis with chymopapain (Chymodiactin, Discase) bears the risk of unpredictable anaphylactic reactions. The rate of anaphylaxis is reported to be between 0.35% and 1.5%. Serological in vitro tests such as RAST (radio-allergo-sorbent test) or ChymoFAST (fluorescent allergo-sorbent test) are used to determine increased specific immunoglobulin E antibody titers against chymopapain in patients submitted to chemonucleolysis. Alternatively, skin prick tests have also been applied in clinical trials. A skin prick test including Discase, Chymodiactin, and Solutrast 250 M, which is a radiopaque dye, has been performed in a total of 257 patients; 222 patients were tested before, and 35 patients were tested after chemonucleolysis with chymopapain. From the group tested before chemonucleolysis, 2.3%-3.3% had positive skin tests. After chemonucleolysis, the overall allergy rate to chymopapain increased to 42.9%. Positive skin reactions seem to be time-dependent--between the 3rd and 12th weeks after chemonucleolysis, more than 70% of the patients had positive skin tests. There was no correlation between a history of previous allergy and the skin test result. Patients with positive skin tests should be excluded from chemonucleolysis. This procedure increases the safety for patients submitted to chemonucleolysis. No anaphylactic reaction has been observed hitherto in more than 350 patients who were treated with the intradiskal injection of chymopapain after a negative skin prick test.

Anaphylaxis↗

Disulfide bond formation between the active-site thiol and one of the several free thiol groups of chymopapain.

Chymopapain, a cysteine protease of papaya latex, has been purified with the use of fast protein liquid chromatography. Two homogeneous fractions were analyzed for thiol content and thiol reactivity. It was found that peak 1 and peak 2 contained two and three thiol groups, respectively, per mole of enzyme. This result is inconsistent with the general belief that chymopapain contains one essential and one nonessential thiol group and suggests that a significant portion of the thiol groups was oxidized in the previous preparations. Such an oxidation can account for some of the inconsistent results reported in the literature. An irreversibly oxidized nonessential thiol group may modify the catalytic function of chymopapain especially if it is close to the active site. That one thiol group resides indeed in the vicinity of the essential thiol group is clearly demonstrated by the biphasic reactions of chymopapain with disulfide compounds such as 2,2'-dipyridyl disulfide and 5,5'-dithiobis(2-nitrobenzoate). In the first step of these reactions a mixed disulfide is formed between the enzyme and the reactant, which is followed by a first-order, intramolecular reaction leading to the liberation of the second half of the disulfide compound. Furthermore, on addition of one Hg2+ ion, 2 mol of thiol group, one essential and one nonessential, disappears concomitantly. Formation of a disulfide bond between the catalytically competent thiol group and another free thiol group of chymopapain under physiological conditions may be of regulatory importance.

Binding Sites↗

[Chymopapain allergy. Diagnostic value of a skin test before and after chemonucleolysis].

Chemonucleolysis with Chymopapain (Chymodiactin, Disease) bears the risk of unpredictable anaphylactic reactions. The rate of anaphylaxis is reported to be between 0.35 and 1.5%. Serological in vitro tests such as RAST (Radio Allergo Sorbent Test) or ChymoFAST (Fluorescent Allergo Sorbent Test) are used to determine increased specific IgE antibody titres against chymopapain in patients submitted to chemonucleolysis for lumbar disc disease. Alternatively skin prick tests have also been applied in clinical trials. A skin prick test including Discase, Chymodiactin and Solutrast 250 M, which is a radiopaque dye used for discography, has been performed in a total of 208 patients. One-hundred and seventy-seven patients were tested before, 31 patients were tested after chemonucleolysis with chymopapain. From the group tested before chemonucleolysis, 2.3-3.5% had positive skin testes. After chemonucleolysis, the overall allergy rate to chymopapain increased to 41.9%. Positive skin reactions seem to be time-dependent: Between the 3rd and 12th week after chemonucleolysis more than 70% of the patients had positive skin tests. There was no correlation between a history of previous allergy and the skin test result. Patients with positive skin tests should be excluded from chemonucleolysis. This procedure increases the safety for patients submitted to chemonucleolysis. No anaphylactic reaction has been observed hitherto in nearly 350 patients who were treated with the intradiscal injection of chymopapain following a negative skin prick test.

Adult↗

Chymopapain for the treatment of intervertebral disc herniation. A preliminary report of a double-blind study.

Sixty patients with unilateral sciatica resulting from lumbar intervertebral disc herniation were entered into a double-blind study. All patients had failed to respond to conservative management, and the diagnosis had been confirmed by metrizamide myelography. Following a randomized schedule, 30 patients had intradiscal injections of chymopapain and 30 patients had intradiscal injections of an equivalent volume of normal saline solution. Complete relief of sciatica was obtained in 63% of patients treated with chymopapain, compared with 27% of saline-injected patients. Six weeks after the injection, 73% of patients treated with chymopapain and 37% of patients treated with saline solution considered that the treatment was successful. The success rate at six months was 80% for patients treated with chymopapain and 57% for saline-injected patients. From the preliminary results of this study, chymopapain is recommended for the treatment of sciatica from intervertebral disc herniation when conservative measures have failed and before disc fragment excision is considered.

Adult↗