TREATMENT

OF BY

LYMAN

LUMBAR

DIRECT

SMITH,

INTERVERTEBRAL

INJECTION

ELGIN,

and

ILLINOIS, UNITED

Chymopapain complex of intervertebral effect

on

is an enzyme

lipid

of nerve

or epidural

No

to disrupt

deleterious

disc Gesler

CLEVELAND,

OHIO,

the mucopolysaccharide-protein

apparent or of the

effect upon dura mater,

effects

of chymopapain

nucleus pulposus of an intervertebral 1963; Garvin, Jennings, Smith and

BROWN,

OF AMERICA

It has no ligaments,

tissue.

injection

LESIONS

CHYMOPAPAIN* E.

JOSEPH

STATES

has the ability

an intervertebral disc. disc, of the longitudinal

the

intrathecal

that

OF

DISC

have

in doses

in that 1965;

the collagen of the nor does it have any

been

more

than

seen

in animals

sufficient

animal (Smith, Garvin, Stern and Smith 1966).

after

to remove

Gesler

and

the

Jennings

Our interest was stimulated by the work of Thomas (1956). He reported that minute amounts of crude papain injected intravenously in rabbits had a profound effect on all cartilaginous tissues of the rabbit’s body. It occurred to one of us that this action of papain might be useful if the enzyme were applied locally in pathological conditions of cartilage usually directly

requiring surgical excision. The first experiments were carried into a transplantable, osteocartilaginous tumour in mice.

impressive, promise.

but subsequent experiments It was soon apparent that

essential.

This

Dr Robert

M

biochemist, intervertebral

.

Dr

intrathecal,

was Gesler

accomplished and Dr Paul

Ivan J. Stern. discs of rabbits

epidural,

potential suffering

as an antigen from herniated

examined.

generous cooperation ; a pathologist, Dr

The activity and dogs, as

or intravenous

muscles, capillaries the cardiovascular

was tested intervertebral

injection.

to chymopapain was applied the possibility

portion

chemical

the

ten

patients

rst

so treated

seventy-five

patients

disc

by this

were

published

treated

and

by

in

1941.

is a major by techniques

precipitation and hydrolysis used by us contained about was administered at p1-I 65 disodium

edetate *

502

Read

as activators.

in part

at a meeting

tissues

such

as Its

Smith

The

details

(1964).

up to now,

were

detected

properly. ofremoving

in these

the offending

of experiences present

The

for from

four

dogs killed

with

report

concerns

to thirty

months.

the

ENZYME

proteolytic enzyme occurring in papaya latex. For these studies, similar to those used for its initial isolation by Jansen and Balls

It is a sulfhydryl enzyme, stable it has a wide spectrum of activity

In vitro

means.

followed,

THE

Chymopapain it was prepared

upon

a

of after

vessels was also investigated, coagulability of blood.

and rabbits. Twenty-two paraplegic treated and those not recovering were

the enzyme in humans

of an intervertebral

tested in hundreds systemic toxicity

Its effect

and larger blood system and the

in guinea-pigs discs were

effects

was and

attributable

first

deleterious

of two pharmacologists, Robert B. Jennings ; and

of chymopapain well as its local

hundreds of experimental animals when In July 1963 we started to investigate

and

No

directed at the intervertebral discs of rabbits showed collaboration with men working in other fields was

with the J. Garvin

intraperitoneal,

the dermis, peripheral nerves, as well as its influence on

out by injecting papain The results were not

over over

a wide a wide

range range

ofpH, and is very soluble in water. of pH, as shown by the rennin-like

of casein, and the hydrolysis of haemoglobin. 500,000 chymopapain-tyrosine unit equivalents in water containing 00l M cysteine hydrochloride Chymopapain of the

British

acts Orthopaedic

very

powerfully

Association,

THE

The

per

preparation gramme. and 000l

It

M

on chondromucoprotein, London,

JOURNAL

OF

in October

BONE

AND

1965.

JOINT

SURGERY

TREATMENT

OF LUMBAR

as shown

INTERVERTEBRAL

by the fact that

DISC

10 micrograms

LESIONS

will discretely

intervertebral disc in an adolescent rabbit. that I milligram may hydrolyse 1 gramme Other proteolytic enzymes tested by us have not shown so favourable a toxicity profile.

All patients operation.

chosen to undergo this A presumptive diagnosis

findings and radiographs list, muscle spasm, and

of the limitation

extremity and limitation of the cauda equina and Twenty-two of the temporary

relief

laminectomy. All complained Their conservative treatment The

immobilisation cortisone injections

patients. variable detail

required

into

years

patients if possible, was not

later, had had experimental

intramuscular, the

had compensation only emotionally used by us but

claims stable had been

to see or contact

if their

TECHNIQUE

The

word

chemonucleolysis

“

of preliminary

amount

of novocaine and The technique

intramuscular now used

into

the

(Fig.

1).

nerve

root

lower

lumbar

The the

the dura and the

could dural

postero-lateral usually sheath

NO.

3,

two tables. and masked

low

back.

The

and

fifty-four

injections

given age

arachnoiditis patient, whose

with not

patients.

They

symptoms

to describe local

obtain

The skin as for any

discs

approach

Pantopaque a mixture

49 B,

epidural drugs

AUGUST

1967

of of

orally

range

was

men.

of ; and from

Twenty-six

could introduce case is described

a in

were

were

not

also

advised

considerably

that

relieved

the

procedure

analgesia. relief

of pain

of

In spite even

“

injection

of

of a considerable with

large

amounts

morphine. After this all patients received general anaesthesia. is as follows : The patient is placed on the left side on

be avoided. comparatively

t

Vol.

and

forms forms

INJECTION

coined

did

and the usual were various

by either

is surgically prepared, operative procedure. the lateral

or the

was

used

At the fifth narrower; is a trade

of isomers

name

ofethyl

exclusively

in the

level the interlaminar if a needle is aimed

postero-lateral

for Jophendylate iodophenylundecylate.

injection,

belief

a

the back is draped Needles are inserted approach

lumbar disc is not investigated unless clinical findings point at that level. The fourth and fifth lumbar discs are examined

compression

Initially

she

intervertebral

third

OF

disc.” was done

medication,

transradiant bridge between and the surgeon is gowned

was

“

the

enough to require analgesics. this method of treatment was

or litigations pending. An attempt was patients for such an untried procedure. used previously by others in twenty-one

treated

be done

chymopapain into an intervertebral In the first patient the injection

with with

followed by catastrophic results (Case 37). was explained to all patients and when possible

previously

should injection.

of a lesion

laminectomy,

women

of a PantopaqueR Our thirty-seventh

a myelograph that was nature of the procedure

laminectomy days after the

lumbar

of lumbar in a lower

in conjunction

relaxant

of the

twenty-one

findings changes

undergone

traction, physicians,

; muscle

ligaments

were

the possibility experiment.

ofa

or symptoms

fusion

intrathecal

exercises

; there

typical sensory

signs

and all had pain severe been prolonged before

; postural

solutions

pulposus

considered to be candidates was made from physical

had and

spinal

spine;

We felt that into a clinical

were

had

lumbar

to seventy-four

an exploratory within a few

had

of

The

they

of sciatica had always

manipulations

of the seventy-five made to choose, Myelography

Four

used were bed rest and employed by us, or other

of sclerosing

twenty-two

lumbar spine. Most patients of motion, with reflex, motor

methods methods

the

the nucleus

method of treatment were of nerve root compression

of pain.

503

OF CHYMOPAPAIN

MATERIAL

prime Other

spinal

;

remove

of straight leg raising. None showed in none was there paralysis of a leg. seventy-five patients had previously

or incomplete

instituted. physiotherapy.

INJECTION

Initial digestion rates obtained in vitro indicate of wet human nucleus pulposus in one hour. either not been as effective, or, if as effective, have

CLINICAL

for

BY DIRECT

that

to probable routinely.

penetration

of

space is commonly wider to penetrate the disc just U.S.P.,

504

L. SMITH

medial

to the

articular

facet,

however, the interlaminar other than in the midline

A lateral

and at

is

an

J. E. BROWN

be lateral

to the

spaces are narrow or the is difficult and penetration

approach

at the upper

levels

is not

dura.

laminae of the

of the third than

or fourth

anteriorly,

the

procedure.

The

on

the screen

of the

lumbar

to the centre first

needle

disc.

One

of the disc.

It should

image

-

- ,

i:: -

‘

to the

the needle sensation

transverse

intensifier

lateral

approaches

process.

T

The

soft

4th

LUMBAR

into the intervertebral

tissues

offer

little

disc.

resistance

unlikely

discs,

position.

The

needle

to the fifth lumbar fourth disc, but is In some patients, seated in relationship the postero-lateral spinous midline. determined

in

the fourth

just

to the

passage

of

resistance offered by bone. There is a characteristic akin to that of pushing a needle into an unripe pear.

is extremely

lateral view, is checked

and

NERVE

structures

to the disc

facet

DISC

to the centre of the disc, more posteriorly. If care

on the position

speeds

CAVA

If the tip of the needle is seen to be anterior not been felt, the needle must be directed anterior

and

of its position

1

for injection

in contrast to the complete when the disc is penetrated,

When, their

at

posteriorly,

is used checks

to the articular

INTERVERTEBRAL

_/

FIG.

superior

problems

)

I

The various

levels,

AORTA

-_

‘/

fourth

: an approach

the needle

frequent

VENA

:

and

anatomical

to direct

with just

ABDOMINAL

third

by these

A portable gradually

be directed

the

spinal needle with stylet is introduced centimetres from the midline, and

has a tendency

is introduced

intensifier.

At

may even overlap dura is common.

confounded

usually rapid and easy. A six-inch long, 18-gauge angle of 45 degrees or more, starting about eight

the level rather

it should

AND

the needles by rotating lumbar

(Figs.

yet disc is taken,

is used

has of

2 to 4).

appear to be properly placed the portable intensifier to disc

penetration penetration

as a surface

guide

in the centre of the the antero-posterior

to the lateral

approach

disc. This needle is inserted at approximately the same site as the one in the directed slightly more posteriorly and approximately 30 degrees distally. either because of a particularly narrow fifth space or because it is deep to the iliac crest, the lateral approach is impossible. In these instances approach is used. A 4-inch, 20-gauge needle is introduced between the

processes of the The needle must by viewing

fifth lumbar and usually be directed

its shadow

on the

first sacral somewhat

image

vertebrae distally

intensifier

about one inch from ; the degree of angulation

screen THE

JOURNAL

(Figs. OF

the is

2 to 4). BONE

AND

JOINT

SURGERY

TREATMENT

OF LUMBAR

The

ease

and

the

are

After taken

of introduction

anatomical

and

peculiarities

*

is made

is given

LESIONS

time

involved

degree

level;

BY DIRECT

vary

individual

to be properly for confirmation

at each

to the

the

DISC

of the

the needles appear in two projections

of HypaqueR weight

INTERVERTEBRAL

this

with

the

505

OF CHYMOPAPAIN

experience

of the

operator

patient.

placed as seen and record. amount

of resistance

INJECTION

on the image intensifier, An injection of 05

is sufficient

experienced

with

for the

diagnosis.

to

Much

injection-a

radiographs 1 millilitre diagnostic

normal

disc

will

--

fr

I FIG.

The

lateral

approach.

3

Figure

FIG. 2-Introduction

of needles.

accept 0.5 millilitre of fluid only if considerable and when the pressure is eased some fluid will disc

will usually Radiographs

diagnostically

and

accept are

1 millilitre taken in

of fluid with two planes.

The

can

be omitted.

Hypaque

diffuses

*

VOL.

49 B,

NO.

3,

force stream

AUGUST

HypaqueR

1967

is a trade

name

Figures

3 and

4-The

4 needles

in position.

is applied to the plunger back into the syringe.

of the syringe, A pathological

ease.

for

sodium

antero-posterior out

of the

diatrizoate,

disc U.S.P.

view

is

space

in a few

of

little

value minutes

506

L. SMITH

so the

films

dissolved discs

should in 05

sterile

water

are

left

in place

as soon

for

five minutes

as possible

and

are

COURSE

Sciatica-Almost

all

had

of those

who

to

sit

thirty-six Loss

then

slowly

AFTER

injection.

Chymopapain,

2 milligrams,

gone were

comfortable

before

removed.

CHEMONUCLEOLYSIS

patients

stand without distressing to forty-eight hours after of leg pain when a patient

or

after

were relieved from Patients who had severe sciatica by the time they were alert after

chemonucleolysis.

leg pain

J. E. BROWN

millilitre of sterile distilled water, is then slowly injected into the disc or the to be causing the nerve root compression. This is followed by 0l millilitre to ensure that all the enzyme has been delivered into the disc. The needles

considered

of

be taken

AND

injection

sciatica within twenty-four hours after even when in bed often stated that their light general anaesthesia. The assessment

if in a flexed

sciatica, was postponed, treatment. first walked was usually

position since

in bed, they

but

were

incomplete.

were

kept

Mild

unable

in bed

residual

for thigh

or calf

ache was often noted with resumption of activity, but this pain subsided completely within the next few weeks. There were two exceptions: after months of observation, each of these patients estimated that residual sciatica was about half of its former intensity and that it was not incapacitating. These two patients had undergone laminectomies before the chymopapain

injection.

Among the early patients in the In two of these discography

lysis.

within

a period

Shortly

after

confirmation

within the

of

two

third

pain-The

after

successful

In all, patients

upon

days

patients

Back

weeks. of these

diagnosis,

or three

forty-eight

patient

of three the

series three experienced no relief following chemonucleoshowed apparent extrusion. All had second injections

any

of the

the

sciatica

had

the

patient

injection.

treated

relieved

injection.

to operate,

for

injection was similar in pattern to that apply to back pain. The back pain that a

variously in two,”

described as a “severe muscle spasm,” a “charley and “ worse than having a baby.” Its onset was

slow ; it usually appeared about six to eight hours after injection twenty-four hours. The spasms were located in the lumbar initiated by activity, reached peak intensity lasting a few seconds leaving

second

subsequently.

drugs were needed. This pain was horse,” “ like I was being broken

the patient

twelve patients a few episodes and stiffness.

the

we decided

following a laminectomy could not be used as a basis to forecast the expect to observe after a few needle tracks had been made for the injection. out of seventy-five cases back pain after injection was severe and analgesic

discomfort

ache,

after

injection

who was not markedly relieved of his symptoms Such a sequel was not, however, encountered among

loss of sciatica after chymopapain laminectomy. The same did not

experienced we might In twenty-eight

was

second

apprehensive

had no complaints of mild to moderate This was generally

of further

attacks.

and usually lasted twelve to region, were not necessarily and then subsided to a dull

In contrast

to such

of back pain or ache after injection. lumbar muscle cramps and a slowly characterised as “ different “ in site

intense

reaction,

Most patients suffered subsiding lumbar ache and severity from that

present before injection. It was usually described as being at one or both posterior superior iliac spines. The side involved bore no relationship to the side of injection or to the side of the sciatica. The duration of this stiffness and soreness varied. Most patients were free from symptoms three or four weeks after injection. In approximately 20 per cent it persisted beyond a month.

In this

subsequent No

visit and correlation

injection

and

the

group

number

typically experienced a considerable lumbar

the

was often has been

soreness

was

described

as progressively

less

described as a stiffening after inactivity. found between the severity and duration

of discs

injected

or

severe muscle spasms list before injection

after who

the

dose

noticeable of back

of chymopapain.

The

at each pain patient

after who

injection was the stocky, muscular man with stated that his sciatica was secondary to his THE

JOURNAL

OF

BONE

AND

JOINT

SURGERY

TREATMENT

OF LUMBAR

back

pain.

and

negligible

Physical

INTERVERTEBRAL

Conversely,

the

backache

appear Before

to lose the list chemonucleolysis,

point

of

tenderness

at this

point

portion

of

the

chemonucleolysis superior spines and was

the point ilium. At

to

after

increase

pressure

was transferred tenderness and

complaint Like

after that

needed

recumbency

the lateral

approach

were

in the

“

in range

Pressure or some

rapidly

lost

one

or

posterior right side

were

both on the

tenderness

after

a few

was used

allowed

process. buttock

was

lumbar

for

laminectomy. circumscribed

to sciatica the

after

of

of lumbar did not

point

chemonucleolysis

found

cases

in the series

yet

spinous

pain.

successful

to leave

injection

when

we were

using

puncture,

it was

worse

days.

and

after

In no

none

hospital

case

of these

at periods

did

it

patients from

two

chemonucleolysis. The three patients who were injected twice kept in hospital for a month. The average stay was five days. On discharge, the patients not restricted in their activities, but were advised to attempt whatever they could do without

as

were were undue

days

that

sciatica

lumbar

than those undergoing showed a constant and

this

at times

of headache. treated early as ten

to

of a lower lumbar or a “ funny feeling

Commonly,

In the last thirty-two

long

of severe

minimal

of paraesthesiae,

rapidly patients

of tenderness times lumbar

to the discs.

and

were

with

comparable

loss

side pain

either

was a prominent

has complained Walking-Patients

was

507

OF CHYMOPAPAIN

injection

injection

was effected on the right side, side and absent on the right.

left

position

before after

power,

radiating

extremity.

approach

upright

signs

any more seventy-five

on

patient

and of the

Headache-Headache the

pressure

the

the chemonucleolysis prominent on the

persist.

physical

INJECTION

or complete return of reflex activity, and recovery showed a severe lumbar list before chemonucleolysis

lower

the postero-lateral in

course

after injection most ofthe

to

caused

complaints

of muscle

leg raising, improvement Those patients who

BY DIRECT

a smooth

of

is, a return

LESIONS

whose

had

diminution

laminectomy-that straight mobility.

patient

usually

signs-The

DISC

discomfort.

weeks;

Those

with

those

after

with

heavy

sedentary

manual

occupations

occupations

usually

returned

returned

to work

within

to work five

within

three

or six weeks.

RESULTS

It is better is

to use the word

the number of patients first seventy-five patients

short,

The

rather

experiences

than

TABLE RESULTS

Results

A

good

“

incapacity

relief

with

work,

pain patient

spinalsurgery

Totals

46

11

57

.

5

6

11

Poor

.

2

5

7

Totals

.

53

22

complete or

causing

years

result.

He suffered

recurrent

protrusion

months

after

.

49 B,

NO.

3,

AUGUST

1967

“

(Case

of

who

for

is actually

and

backache,

defined as marked, work. A “ poor “

is

“

with

no

but result

incomplete, implies no

residual

worse.

had not had of an intervertebral

16).

I).

75

sciatica

Fair

incapacity

category

of twenty-five

chemonucleolysis

relief

avocations.

in this

of follow-up

and recurrent. injection (Table

I

Fair

not

the period

CHEMONUCLEOLYSIS

spinaisurg:ry

patient

VOL

AFTER

.

implies

one

because

Good

sports,

residual

improvement;

One

result

“

for

results,

few, and the condition so typically chronic were assessed four to thirty months after

previous

operation disc

at another

obtained level

a

“

good”

twenty-three

508

L. SMITH

All

seventy-five

patients

were

assessed

frequent critical analyses by visiting were a feature of the assessment. Among

the

twenty-two

AND

by personal

colleagues.

None

patients

J. E. BROWN

Serial

examination lumbar

had

authors,

and

by

and extension radiographs was assessed by questionnaire.

of the patients

who

by the

flexion

undergone

previous

spinal

operation

one

had

had three laminectomies and is rated as good. Eight had had two laminectomies ; two are rated as good, four as fair and two as poor. Thirteen had had one laminectomy; eight are rated as good, two as fair and three as poor. Four patients had had spinal fusions associated with laminectomy ; two of these are rated as good and two as fair. The latter two have lost their

sciatica,

but

a lessened

Seven operation.

patients are The details

(Case

the

37);

degree

of back

pain

persists,

which

rated as poor results. Two of response to chemonucleolysis

particulars

of the

other

Case

1-A forty-year-old woman lost back pain was severe and unremitting. lumbar area and now was associated

is not

incapacitating

for work.

of these had not had previous of one of these are described

spinal later

are as follows:her severe

left sciatica

After three with a right

weeks the sciatica.

four

hours

back pain Laminectomy

after

chemonucleolysis,

became localised showed no

but

in the right pathological

findings save for a small free fragment of fibrocartilage at the fifth lumbar level on the right. She was relieved of right-sided sciatica, but some back pain persisted. There was gradual return of left sciatica in the following year. Since that time, multiple consultations with many types of specialists, another been

laminectomy by a neurosurgeon, unavailing in relieving symptoms,

was claiming

a patient Five spinal

compensation

and

was a poor choice of the

seven

operation.

intractable

pain

neurosurgeons.

injection

had

as the first candidate

before

for

patients

Two

whose

of these

following Treating

and all manner of physical therapy which are unsubstantiated by objective

results

patients

were

(Cases

laminectomy. these patients

received this

rated

33 and

psychiatric

clinical

as

and medications findings. This

treatment.

have patient

Obviously

such

experiment.

poor

“

57) were

In both cordotomy by chemonucleolysis

“

had

undergone

seventy had was

years

previous

of age

and

had

been recommended more compassionate

by than

objective; neither of the two experienced relief. Two other patients (Cases 51 and 52) did not experience significant relief of pain, but did show notable regression of physical signs. Neurosurgical consultation was obtained in each, and myelography was read as negative. In each

case

was

found

a

second laminectomy was done at any of several levels explored,

by displaced

intervertebral

found

Radiographic multiplicity

Neither

patient

experienced

relief

abnormality

compression

of symptoms

after

patient in this group (Case 38) had not been relieved of low back pain by two laminectomies. After chemonucleolysis she was only partly relieved of for six months and it then recurred in its original intensity. Eight months later

and sciatica her sciatica was

tissue.

No

root

The fifth

laminectomy.

she

disc

by the consultant neurosurgeon. nor was there evidence of nerve

to be suffering

changes of discs

from

generalised

after injection-In injected

is explained

lymphosarcoma. patients by our early scepticism

the seventy-five

I 35 discs were injected. about the infallibility

The of the

discograph. Recently we have been more discriminating in our decisions. Of the 135 disc spaces injected, many showed appreciable narrowing within five to seven days, and all except thirteen showed some degree of narrowing on radiographs taken within a month ofinjection. Twelve discs showed slight continued narrowing two months after injection. The degree of narrowing varied from something less than 10 per cent to as high as 60 per cent. We are unable to correlate the degree of narrowing with the amount of enzyme injected, the age and uninjected

size of the patient, discs

have

shown

or the apparent

pathological

state

of the injected

disc.

No adjacent,

narrowing. CASE

REPORTS

Case 20-This is an example of the forty-six patients who had had no previous spinal operation showed good results from chemonucleolysis. A thirty-eight-year-old man did heavy work as for a telephone company. He had suffered intermittent, incapacitating attacks of back pain sciatica for four years. The most recent episode had been unrelieved by seventeen days of THE

JOURNAL

OF

BONE

AND

JOINT

and who lineman and left bed rest, SURGERY

TREATMENT traction

and

limitation aspect

lower

OF LUMBAR

INTERVERTEBRAL

physiotherapy.

The

DISC LESIONS

physical

findings

BY DIRECT

included

INJECTION

a flat

back

509

OF CHYMOPAPAIN

with

list

to

the

right,

marked

of the left straight leg raising, loss of the left ankle jerk, and hypoaesthesia over the lateral of the left foot. He estimated his pain to be 50 per cent in the back and 50 per cent in the left

extremity.

L

.. ... 5

FIG.

7

FIG.

fifth

20. lumbar

and

8-Radiographs

Case

Figure levels.

one

injection In October levels sciatica

back

(Fig.

1963

5).

disappeared

for four

49 B,

NO.

was

3,

AUGUST

1967

taken there

hours

after

gradually on the day was apparent

8

showing

protrusions at fourth and before injection. Figures 7 7) and five weeks (Fig. 8) after of spaces after injection.

as showing

9 milligrams,

six

but this subsided

(Fig.

narrowing

interpreted

solution,

were injection

week

showing

approximately

days,

Lateral radiographs 6 to 8). A week after VOL.

a discograph

Chymopapain

FIG.

5-The discograph Figure 6-Radiograph

was

into

chemonucleolysis.

and

he returned

of injection, narrowing

at the fourth and fifth lumbar each disc. The patient’s left

protrusions

injected

He

to work a week later, of the fourth

complained

in four and and

of

a sore,

stiff

weeks. five weeks fifth spaces.

later (Figs. A month

510

L. SMITH

later

the narrowing

past

twenty-four

without

of the fourth months

back

pain

have

space

shown

had

AND J. E. BROWN

increased.

no further

Subsequent

change.

The

films

patient

taken

has

at intervals

continued

during

to do heavy

the work

or sciatica.

Case 2-This

is an example from the group of eleven patients who had had previous spinal operation and who obtained ‘ ‘ good “ results after injection. A thirty-two-year-old man had a laminectomy in 1962 for removal of a protruded disc at the fourth lumbar level. He had relief of his right sciatic pain for approximately by

two months, bed rest and indeterminate findings.

two

weeks

showed limitation

of

ankle jerk, 25 per cent

but then suffered a recurrence. Pain had not been relieved or diminished physiotherapy in the hospital. Myelography one week before injection Physical examination revealed a lumbar list to the left with marked

of

lumbar

extension,

and hypoaesthesia in the back and

slight

limitation

of

FIG. 9 Case

Figure five

(Fig.

9 shows

lumbar or

hours

six

Case 23-A and

were:

after

pain

marked

of

16 milligrams

has been Radiographs intervertebral

complete

loss

75

and

cent

per

degenerative

in the

changes

disc

with

back

limitation

and

25 per

cent

a 20-gauge hours

after

slight

low back

pain.

He returned

seven

months

no complaints

needle. to work

in the

The eight

right

two

extension,

jerks. lower

patient

extremity.

stated

or extremity

the

gone

weeks

vigorous of the

because

of back

findings

limitation

of right

estimated

that

Radiographs

his

showed

12).

discharged

after

after

at

three

The physical

marked

The

11)

had

officer

months

bed rest.

right

to be

injected

two years despite showed narrowing

at the fourth lumbar level only, because we were unable

patient weeks

for

(Fig.

sciatica

as a police

of

the

pain

11

was

his right

the past injection

month

ankle

level (Fig.

He was

of back

one

and

suggested protrusion injected at that level injection.

that

incapacitated

of lumbar

knee

his

months

milligrams,

stated

to his occupation

after

of the right

twenty-one spaces.

10

patient

was

at the lumbo-sacral

twelve had

The

worker

of

estimated

FIG.

Chymopapain,

fifth.

improvement

lordosis,

approximately

has

1963.

dairy

no

depression

In October 1963 a discograph milligrams of chymopapain were

lumbo-sacral

July

depression

He

10

He returned

male was

raising,

foot.

from sciatica and back pain for of the lumbar spine taken after spaces (Figs. 10 and 1 1).

of lumbar

leg raising,

leg

right

free

fifty-seven-year-old There

straight

three months (Fig. 10) and narrowing of the intervertebral

at the

chemonucleolysis.

He

sciatica.

was

radiographs Note the

discograph

and

right

straight

9) and injection.

the

level

after injection. physical activity. fourth and fifth

pain

FIG.

2-Discograph

fourth

right

of the plantar aspect of the 75 per cent in the extremity.

that from

his the

right

pain, THE

even JOURNAL

sciatica

hospital

chemonucleolysis

(Fig. 13). to penetrate

one

Nine the

disappeared

week

later

with

and in the past twenty-

though OF

his BONE

occupation AND

JOINT

entails SURGERY

TRE ATMENT

frequent space

OF LUMBAR

lifting twelve

of milk

days

INTERVERTEBRAL

cans weighing

after

injection.

DISC LESIONS

BY DIRECT

INJECTION

100 pounds. Figure 14 shows the narrowing Radiographs taken at Varying intervals since

OF CHYMOPAPAIN

511

at the fourth lumbar have shown no further

narrowing.

FIG.

FIG.

12

13

FIG.

14

Case 23. Figure 12-Radiographs before injection show marked degenerative changes. Figure 13-The discograph. There is a suggestion of protrusion at the fourth lumbar level. Figure 14-Narrowing of the fourth lumbar space twelve days after injection. Compare with

Case 18-A a period

twenty-six-year-old

man

of eleven years. When by bed rest. Examination

unrelieved and limitation

suffered

first

seen,

12.

recurrent,

incapacitating

he complained

VOL.

49 B,

NO.

extension.

3,

1967

AUGUST

There

complete

of right

was a palpable

loss

attacks

sciatica

of low

back

of five weeks

pain

over

duration,

of lumbar lordosis with a list to the left, shelf at the fifth lumbar level. Straight leg raising was limited on the right, but the knee and ankle reflexes were equal and active and there were no sensory changes. He estimated his pain to be 75 per cent in the right low back and 25 per cent in the extremity. Radiographs showed a minor degree of spondylolisthesis at the lumbo-sacral level

of lumbar

showed

Figure

L. SMITH

512 with a defect (Fig. 16). milligrams the injection,

AND J. E. BROWN

in the pars interarticularis at that level (Fig. I 5). A discograph was done in October 1963 Chymopapain solution, 8 milligrams, was injected into the fourth lumbar disc and 10 into the fifth. The patient stated that he had complete relief from sciatica six hours after but a diminishing degree oflow back pain and stiffness persisted for six weeks. A radiograph

:

I

I

FIG. 17 the spondylolisthesis 17-Six weeks

3.

18. interarticularis

Figure

Case

15-Radiograph defect. Figure

There taken

six weeks

January

1966

after the

is marked

injection

patient

further narrowing. Case 16-At the time has been encountered.

had

before 16-The

narrowing

showed no

injection. discograph.

of the fourth

marked

complaints

narrowing of

back

Note Figure

and

fifth

at both

or leg pain.

lumbar levels

with pars injection.

after

spaces. ( Fig.

Subsequent

I 7).

When

radiographs

assessed

have

in

shown

no

back

pain

and right

of writing, one case A twenty-five-year-old

sciatica.

His symptoms

of recurrent man was

disc protrusion disabled for ten

were unrelieved

by various THE

following chemonucleolysis months because of right

measures,

JOURNAL

OF

including BONE

AND

low

a chairback JOINT

SURGERY

TREATMENT

brace

OF LUMBAR

and

seven

INTERVERTEBRAL

weeks

of

findings

were

was

done

and

9 milligrams, was injected back pain or sciatica, and of narrowing that time

At

chymopapain disappeared slowly

and

it was

at the fifth

traction

and

and

BY DIRECT

cent

He

in the right

injected showed

estimated

lower

his

extremity.

pain

The

to

be

physical

level. Accordingly, 10 to 20 per cent

the patient was not relieved of his ten days after injection showed no

three weeks of narrowing

later, a second injection was at the fifth lumbar level, so

only at the fourth lumbar level. The patient stated that his sciatica six hours after the second injection, but back stiffness and soreness subsided

months

before

he

returned

to

manual

work.

Radiographs

taken

in

January

narrowing at the fourth lumbar space estimated to be 30 to 40 per cent and narrowing lumbar space estimated to be 10 to 20 per cent (Figs. 18 and 19). Until September 1965

-

FIG.

Case

he had

513

OF CHYMOPAPAIN

at the fourth lumbar level. In October 1963 at both the fourth and fifth levels. Chymopapain,

-

the patient

INJECTION

physiotherapy.

50 per

nerve root compression as questionably normal

at either radiographs

three

LESIONS

at each of these levels. After injection radiographs of the lumbar spine taken

was injected approximately

I 964 showed

rest,

in the back with read

compatible

discography

evidence done.

bed

50 per cent

approximately

DISC

16-Radiograph (Fig. 19).

onset

FIG.

before injection Note the marked

was free of symptoms

a sudden

___

18

even in the

of pain

with right

19

(Fig. 18) and three months after the second narrowing of the fourth and fifth spaces. heavy physical activity; low back accompanied

injection

then, after a severe lifting strain, by right sciatica. His symptoms

were unrelieved by three weeks of bed rest, physiotherapy and traction. The physical findings suggested nerve root compression at the fifth lumbar level. A laminectomy was done in October 1965. A large nuclear

protrusion

ligament

was

was intact.

explored. operation.

The patient’s He has been

It is noteworthy second

found

injection

operation

that

at the

to be associated

mature

this

appearances lumbar

appearances 49 B,

VOL.

H

lumbar

with

level

were

otherwise

was rapid work for the

patient’s

fourth

lumbar

and past

symptoms level.

a herniation

and

removed

The

he returned two months.

were

The

was

negative.

relieved

recurrence

at the fifth lumbar

2 grammes. The microscopic tissue removed from patientswho were seen interspersed with

to

and

; the

posterior

fourth

lumbar

light

work

physical

three

signs

of pain

and

sciatica

level.

The

fragment

longitudinal

level was not weeks

lessened

in I 965

after

by the proved

of herniated

appearance of the fibrocartilage was had not had previous chemonucleolysis. areas of apparently normal fibrocartilage

at

disc no

chondrocytes.

Histological human

fifth

at operation

convalescence doing heavy

removed at operation weighed different from that ofthe same Areas of focal degeneration

with

at the

Findings

NO.

after

injection-We

discs which were removed have been unremarkable. 3,

AUGUST

1967

have surgically Chymopapain

examined after

histologically chemonucleolysis. affects only the

portions The

of five other histological

chondromucoprotein

514

L. SMITH

of the

disc,

affected which

leaving

the

further

expect

chymopapain surgical

to

intact.

see

widening We

animals

of

had

only

can

to be responsible

of some

people

chondrocytes

seen

been

for the

this

injected

be expected

in

with

disc

spaces

man,

but

appear

to be directly

previously it has

the

breakdown

of disc

that the cure the hormonal of the

after

observed

in

three

Chemonucleolysis,

symptoms

would speculate or anticipating

of cartilage, One might

narrowed

been

chymopapain.

to relieve

original

do not

likewise

the chondromucoprotein matrix degree after chemonucleolysis.

intervertebral

not

can be considered a “ cure.” We biochemical method of preventing

believed

J. E. BROWN

synthesise to some

have

who

extirpation,

The

Chondrocytes be replaced

injection.

experimental sense some

collagen

(Thomas 1956). might, therefore,

AND

disease

like and

in no

of disc disease awaits or metabolic influence

chondromucoprotein

in the discs

1962).

(Naylor

COMPLICATIONS

CHYMOPAPAIN

OF CASE

INJECTION

REPORTS

Case 37-One patient, the thirty-seventh A fifty-six-year-old man endured acute

in this series, suffered severe complications after injection. back pain and left sciatica which were unresponsive to conservative measures, including two weeks of bed rest and traction. The physical findings were compatible with nerve root pressure at the fourth or fifth lumbar level. A myelograph revealed a persistent filling defect between the fourth and fifth lumbar vertebrae. It was estimated that approximately 5 millilitres of PantopaqueR were left in the subarachnoid space. Five days later discography was done by the postero-lateral approach at the third, fourth and fifth lumbar levels. Difficulty was encountered in gaining entrance to the fifth lumbar disc space and multiple dural punctures were probably made before the needle was properly placed. The discographs were read as showing degeneration at the third and fifth lumbar levels and extrusion at the fourth level with epidural leak of the contrast medium. Chymopapain, 10 milligrams, was injected into each disc. The patient’s sciatic pain disappeared six hours after injection, but he complained of severe back and abdominal pain. For the ensuing five days he showed signs of an unlocalised acute abdominal crisis of such severity as to raise the question of exploratory laparotomy. Seven days after the injection, the patient’s abdominal distress was subsiding and he had no complaint of back or extremity pain, but some weakness in dorsiflexion of the left foot was noted. On the tenth day he was paraplegic. Laminectomy from the fourth thoracic to the fifth lumbar vertebra showed normal tissue save for a haemorrhagic arachnoiditis centred at the tenth thoracic level. There was no evidence of protrusion or extrusion at the third, fourth or fifth lumbar disc spaces. There was no recovery from the paraplegia. Discussion-This

experience

prompted

a reassessment

of the

toxicity

of chymopapain

when

injected intrathecally or epidurally. Experiments in rabbits, cats and dogs were repeated (Garvin and colleagues 1965) and were extended to include the rhesus monkey. These experiments showed that chymopapain injected intrathecally or epidurally in a human could not initiate the clinical events observed in this patient. ln none

ofthe

at necropsy.

When

hundreds

ofanimals

injected

chymopapain

with

chymopapain

intrathecally

is injected

have

we found

in sufficient

quantity

it causes bleeding from the poorly supported vessels of the usually dies in a few hours with increased intracranial pressure. to be a haemorrhagic in 50 per cent per kilogram needle

in the cerebello-medullary

millimetres kilogram

of saline to of cerebrospinal

the animal abnormal

window

phenomenon

cistern more fluid

and

may

be alleviated.

in a rabbit,

bent one

needle, and

30

than 400 is removed

a half

a one-quarter milligrams inches

For

to be toxic,

and the animal produced appears example,

injection is 025 milligram per kilogram. in the lumbar area, a water manometer will

show

a rise

millimetres by cisternal

from

a normal

in fifteen puncture

will survive with no neurological sequelae; necropsy features. This sequence was confirmed by Macnab

laminectomy long,

pressure

of dogs after intrathecal is injected intrathecally

pia-arachnoid The toxicity

arachnoiditis

inch

square

of chymopapain cephalad.

This

window

dose

was

was instilled

were

300 THE

times JOURNAL

dose

of approximately

minutes. If the pressure done (1965)

lethal

If 1 milligram attached to a 45

1 millilitre will drop

per and

months later shows no in another way. After

cut

in the

dura

intrathecally the OF

lethal BONE

and, through

intrathecal AND

JOINT

with

a the

dose SURGERY

TREATMENT

OF LUMBAR

INTERVERTEBRAL

animal. The rabbit

The laminectomy survived without

for such injection.

an

operated

as a vent

for the

DISC

resulting

LESIONS

wound, apparent

increased

BY DIRECT

but

INJECTION

not the deleterious

cerebrospinal

OF CHYMOPAPAIN

window, effects.

fluid

was closed The dural

pressure.

observation in cats. Our patient received a chymopapain dosage of 10 milligrams discs. Even if this total chymopapain dosage of 30 milligrams had

515

after the window

We have

confirmed

this

one

would

have

expected

pressure, but this What caused

was the

Butler 1963) and for five to seven

the

patient

not so. paraplegia?

of retained

fifth

lumbar

have

shown

some

It has

been

pointed

out

signs

of increased

by others

intracranial

(Howland,

Curry

and

confirmed by us that 2 or 3 millilitres of Pantopaque’ retained intrathecally days in a dog will regularly cause arachnoiditis. If some of the dog’s own

blood is then injected intrathecally commonly results in paraplegia. amount

to

in each of three lumbar been injected intrathecally,

a few days later a more This sequence probably

Pantopaque

level,

and

for

intrathecal

five

days,

a difficult

severe occurred

transdural

reaction will ensue which in this patient : a large needling

procedure

at the

haemorrhage.

Case 31-Another

patient caused us considerable concern. He was a fifty-one-year-old engineer who had suffered neck, shoulder and arm pain for more than a year without relief from conservative measures. Discography by the antero-lateral approach demonstrated a “ ruptured disc “ at the sixth cervical level and this disc was injected with 10 milligrams of chymopapain through the same needle. His pain was partially relieved for two weeks, but then recurred with increasing severity, and in the subsequent six weeks he developed a Brown-S#{233}quard syndrome. An operative exploration was made by a neurosurgeon who found an extramedullary, intradural vascular mass at the sixth cervical level, fed by an artery coming through the dura. A tiny biopsy specimen was read as “ consistent with granulation tissue,” and he made a clinical diagnosis of pseudoaneurysm, which he apparently felt was caused by lytic action of chymopapain on the artery. Approximately four months after the diagnosis paralysis

of pseudoaneurysm and, on this occasion,

had

been made examination

the patient was operated upon again because of worsening of the mass removed showed the lesion to be a malignant

haemangioendothelioma. This cervical

For

this

patients

Case

case

shows

region

as

reason, with

27-A

the

difficulty

compared

we have lumbar

to

confined

pain

and

forty-three-year-old

of

that

diagnosis

in the

in

lumbar

all subsequent

the area.

trials

to

sciatica. man

suffered

intermittent

attacks of low back pain with left sciatica for five years. He had been incapacitated for seven weeks by a severe episode of pain unrelieved by bed rest, physiotherapy and traction. Physical findings were considered to be typical of a disc lesion at the fifth lumbar level. In October 1963 discography was done by the posterolateral approach and showed a probable extrusion at the fourth lumbar level and a protrusion at the fifth (Fig. 20). Chymopapain, 10 milligrams, was injected at the fourth lumbar level and 7 milligrams at the fifth lumbar level. The course after injection was unusual in that he lost his back pain and lumbar tenderness in a few days, but his left sciatica persisted. Three weeks after the first chemonucleolysis the findings at discography were unaltered, so a second injection was done. Chymopapain, 9 milligrams, was injected into the fourth and fifth discs. Immediately after the injection the patient manifested anaphylactic shock with a marked fall in blood pressure and a diffuse pilomotor reaction with erythema of the skin. He was treated with intramuscular steroids and vasopressor drugs and recovered within an hour. He lost his sciatica within twelve hours and was discharged from the hospital six days later. Three weeks later his serum was tested for antibodies against chymopapain. None was VOL.

49 B,

NO.

3,

AUGUST

1967

FIG.

20

Case 27-The discograph showing epidural leak of the contrast medium.

516 demonstrated used

for

by various discography

Chymopapain patient’s

so

is

positive

and

precipitation

that

occasion

a

on

relatively

poor

for guinea-pigs than showed no antibodies

serum

we

AND

agglutination was

anaphylactogenic

L. SMITH

that

assumed

the

acute

J.

E. BROWN

tests. but

antigen,

ovalbumin against

Intradermal

negative

being

reaction

the

twenty

times less than three weeks

was

to

Hypaque’

later.

approximately

and forty chymopapain

hypersensitivity

test

a week

probably

times

less

horse serum. This after the injection,

caused

by the

contrast

medium.

Case 56-A

thirty-two-year-old

lysis. He responded of

a disc

had suffered to bed rest, lesion

at

the

furniture

from severe physiotherapy

fifth lumbar

Figure

vertebra,

22-Ten

FIG. oflysis

to

months

in the

disc later

lower

space the

Discography

fifth

The

respectively.

from

in October

at the

hospital

patient

in four

days

gradual onset of low back the buttocks or extremities. that time the sedimentation

in the lumbar fifteen fourth

and 1965 space

weeks lumbar

has had

cause rate

area.

1964

lumbar

level.

stated

that

and

returned

diagnosis

after injection showed vertebra (Fig. 21).

no complaints

showed filling (Fig. 22).

ofthe

lytic

area

in of the

infection

after

chemonucleo-

seven weeks, were considered

which had not to be typical

were

in.

of back defect

about

in the

vertebral

fourth

lumbar

injection.

disc

space

has

hours

muscle

three

fourth later. two

spasms

weeks

“

since

then. without

THE

later he noted a radiation into

when

Radiographs continued

JOURNAL

but during

were negative, to palpation

made

and

He was discharged

weeks without

in the inferior portion to his heavy occupation

body

level

of chymopapain

of hospitalisation,

radiographs tenderness

was finally

lumbar

4 milligrams

However, “

infection

pain

2 and

eight

lumbar moderate

an area of destruction The patient returned

or extremity

fourth

after

at the

with

in a month.

Repeated and only

of low grade

The

degeneration injected

he lost his sciatica to work

22 ofthe

weeks

is filling

apparent discs

obscure. elevated

body

further.

pain which increased to severe This severe pain subsided after

of the pain was was only slightly

The

showed These

part

infection-fifteen

not narrowed

protrusion

a disc space

and left sciatica for His physical findings

21

21-Area

secondary

Figure

developed

level.

FIG.

Case 56.

mover

low back pain and traction.

blood found

radiographs

taken

of the body in February

of the 1965

taken narrowing

OF BONE

the was

AND

in November of the

JOINT

disc

SURGERY

TREATMENT

OF LUMBAR

Case 19-A

fifty-one-year-old

right

sciatica.

fifth

INTERVERTEBRAL labourer

Discography

lumbar

level.

DISC LESIONS had

showed

for

several

degeneration

Chymopapain,

BY DIRECT months

at the

8 milligrams,

was

INJECTION

suffered

fourth

incapacitating

lumbar

injected

at the

level

fourth

but

lasted

Neurological Laminectomy The patient’s pain. For arachnoiditis.

untoward : giant

days

a few

after

minutes.

effects-Other

urticaria

injection

ten

are

they

were

not

32);

(Case

months

following

attributable

side

non-specific

days

after

injection

unexplained

(Case 24) ; a Marie-Striimpell myocardial infarction fifteen fourteen

When

present

level

the

pain

protrusion and

and

at the

10 milligrams

although less severe. back pain, localised times a day and were

patient

had

no

symptoms.

examination was negative, but a myelograph showed a block at the fourth lumbar level. by a neurosurgeon revealed a small area of filmy arachnoiditis at the fifth lumbar level. convalescence was good and he experienced considerable, but incomplete, relief of back the reasons expressed previously chymopapain was not considered a cause of the

Incidental include

only

back

and

at the fifth level. Sciatic pain disappeared in five hours, but back pain persisted Seven months later the patient was admitted to hospital because of persistent over the sacrum. This pain and spasm were intermittently present one or two severe,

517

OF CHYMOPAPAIN

effects recorded 40) ; a recurrence

(Case

gastrointestinal

after chemonucleolysis of acute glaucoma

bleeding

one

month

after

four

injection

type of arthritis one year following injection (Case 43); a massive months after chemonucleolysis (Case I 1 ) ; and lymphosarcoma injection

(Case

38).

We do not

feel that

any

of these

complications

to chymopapain.

DISCUSSION

The symptoms caused by a lumbar intervertebral disc lesion can be relieved by removing offending disc tissue either surgically, or chemically by the injection of chymopapain into disc. When protruding or extruding disc material removed at operation is used as a

the the

substrate

for chymopapain

collagenous 44

per

is

a

parts

cent

of this

very

so

can

the

and

weight

of

portion action

tube,

the

disc

tissue.

its

The out

it has not This

1966).

(Mitchell,

total

Hendry

because

is dissolved

The

collagen

and

the

Billewicz

water-binding

capacity

and

been

may

recovered

be the

result

at zero

of in

When

time.

of interaction

then

sciatica

is unknown.

even

the

mass

of

the

pressures

sufficiently

most

injected

It apparently

between

its

space (Schubert of the chondro-

reducing

is of

but

properties

markedly

the

represents

1961),

water-trapping

degraded chondromucoprotein of the disc. The rapid loss

whereas

remaining

cause it to occupy several thousand times more of chymopapain is to disrupt the fine structure

removing

disc,

chondromucoprotein

Smith

be explained by this mechanism. ultimate fate of the injected enzyme

intervertebral to the

by dry

structures. size to diffuse

best The

test (Stern

percentage

chondromucoprotein 1964). The probable mucoprotein,

unaffected

material

small

contiguous molecular

in the

are

of

into bonds

on

small

our

patients

an

animal’s

immediately

negatively

charged

acid

mucopolysaccharides and the enzyme which is positively charged at pH below 9. The enzyme has been tagged with I’s’ before injection, but recovery studies have been inconclusive. Tagging with C14 has not been done. The length of activity of the enzyme in vivo is limited by natural antagonists. For example, after intrathecal injection of 20 milligrams of chymopapain in a dog and

because in

weighing

vivo

radiopaque We

the

hour. study

effectiveness

experiments. have

a degenerated is another VOL.

20 kilograms,

none after one A double-blind

not

conducted

thousands

agents and cortisone found the diagnostic

3,

1967

of the during was

activity

may

the clinical

adequately

of intervertebral

that

disc. Whether it is whenever

be found

disc

after

investigation

demonstrated

may be considered controls. accuracy of discography

a normal intervertebral We have assumed

AUGUST

cent

of chymopapain The

and matter.

49 B, NO.

was

20 per

injections sufficient

the degenerated the discograph

thirty

minutes

of chymopapain in the done

by

to differentiate

in vitro others

and with

between

disc causes symptoms shows a protrusion

518

L. SMITH

into

the

spinal

canal

longitudinal

ligament.

ligamentous

tear

or

does

nerve

of disc

narrowing

period

after

of the

that

dye,

escape

necessarily

compatible of

indicate

reaches them, breaks seventy-five patients

our

of these claimed no evidence that

intraforaminal

J. E. BROWN

with

a liquid

that

a rent

such

nuclear

as

in the

HypaqueR

material

also

posterior through

has

a

extruded.

into the centre of the disc bonds immediately to its preferred substrate, Evidently, in the case of an extrusion with nuclear fragments lying

epidurally, chymopapain Thus, twenty-two of twenty-one We have

leak

realise

not

Chymopapain injected chondromucoprotein.

and

epidural We

AND

root

after

a rapid loss of their the rapid narrowing

pressure,

or lumbar

laminectomy,

operation.

He

them down, and showed epidural

found

found

no

pain

relieves nerve root pressure. leak of dye at discography,

sciatica. of injected from

it in 74 per

relationship

discs

instability. cent

of spines

between

causes

Alfred

the

sciatica

(1951),

studied

degree

over of

by

in a study a ten-year

narrowing

and

residual or recurrent symptoms. All our patients have been followed to date by flexion and extension lateral radiographs at frequent intervals. On these films, many show evidence of some instability as described by Harris and Macnab (1954) but none has as yet complained of lumbar pain related for a spinal fusion.

to activity Thus, our

arthrodesis

segments

of lumbar

Some of the first as 16 milligrams.

high

amount that 2 milligrams chronic

in conjunction

patients We

a temporary rise in urinary after chemonucleolysis. days

after

is

largely products

in the chondroitin from the displaced

relieving

this

disability

injection,

An

account

pain

is most

after

which

on

the

starting investigations disc lesions. We await

fair

Although

that

was

untoward

cases

with

a new

intervertebral

disc

lesions

has

a

proteolytic

deleterious

injected into Two milligrams

effects

levels.

and

reactions

The

represents simple

increase

absorption method

of

“

poor have

“

(9 per been

this method of chemical of our experiences.

method been

enzyme,

upon

intervertebral discs per disc constitute

patients who were four to thirty months

(15 per cent)

in humans with their confirmation

in seventy-five by

without

to seventy-five followed for “

to pre-injection

has been detected one or two fold

CONCLUSIONS

AND

chymopapain,

material

Chymopapain lateral approach.

“

caused

fact

disc

administered patients were

3.

sciatica

it recedes

excretion approximately

appealing.

of experiences

and

intervertebral

cent),

into the disc as find the minimal

is adequate. It is reassuring that rhesus monkey without acute or

sulphate C fraction. We believe this substance disc material ; if this is so, such a comparatively

Other clinicians are upon intervertebral

is based

2. the

of chymopapain the dosage to

acid mucopolysaccharide Excretion is increased

SUMMARY

1.

laminectomy.

ill effects.

for one to three

back

with

in this series received doses have been gradually reducing

is effective. A dose of 2 milligrams per disc can be injected intrathecally in a five-pound

Recently, in our patients

attack

and relieved by immobilisation that would indicate the need results provide evidence against the argument for routine

can

adjacent

of treatment

presented. break

down

method displaced

tissues.

by the postero-lateral an effective dose.

potential candidates and results were

of low

The

for graded

The

or preferably enzyme was

laminectomy. as “ good

“

These (76 per

cent).

encountered,

none

of these

has

been

attributable

to chymopapain. 4.

Our

disc

lesion

investigations is a safe,

have effective

convinced method

us that enzymatic dissolution of relieving sciatica and

ofa lumbar intervertebral low back pain in selected

cases. THE

JOURNAL

OF

BONE

AND

JOINT

SURGERY

TREATMENT

OF LUMBAR

INTERVERTEBRAL

DISC LESIONS

BY DIRECT

INJECTION

OF CHYMOPAPAIN

519

REFERENCES ALFRED,

K. S. (1951): Surgical Treatment of Herniated Lumbar Intervertebral Discs. American Journal of 81, 390. GARVIN, P. J., JENNINGS, R. B., SMITH, L., and GESLER, R. M. (1965): Chymopapain: A Pharmacologic and Toxicologic Evaluation in Experimental Animals. Clinical Orthopaedics and Related Research, 41, 204. HARRIS, R. I., and MACNAB, I. (1954): Structural Changes in the Lumbar Intervertebral Discs. Journal of Bone and Joint Surgery, 36-B, 304. HOwLAND, W. J., CURRY, J. L., and BUTLER, A. K. (1963): Pantopaque Arachnoiditis: Experimental Study of Blood as a Potentiating Agent. Radiology, 80, 489. JANSEN, E. F., and BALLS, A. K. (1941): Chymopapain: A New Crystalline Proteinase from Papaya Latex. Journal ofBiological Chemistry, 137, 459. MACNAB, I. (1965) : Personal communication. MITCHELL, P. E. G., HENDRY, N. G. C., and BILLEwICZ, W. Z. (1961): The Chemical Background of Intervertebral Disc Prolapse. Journal ofBone andJoint Surgery, 43-B, 141. NAYLOR, A. (1962): The Biophysical and Biochemical Aspects of Intervertebral Disc Herniation and Degeneration. Annals ofihe Royal College ofSurgeons ofEngland, 31, 91. SCHUBERT, M. (1964) : Intercellular Macromolecules Containing Polysaccharides. Biop/zysical Journal, 4, Supplement I, 119-138. SMITH, L. (1964): Enzyme Dissolution of the Nucleus Pulposus in Humans. Journal ofthe American Medical Association, 197, 137. SMITH, L., GARVIN, P. J., GESLER, R. M., and JENNINGS, R. B. (1963): Enzyme Dissolution of the Nucleus Pulposus. Nature (London), 198, 1311. STERN, I. J., and SMITH, L. (1966): Dissolution by Chymopapain in vitro of Tissue from Normal or Prolapsed Intervertebral Discs. Clinical Orthopaedics and Related Research, 50, 269. THOMAS, L. (1956) : Reversible Collapse of Rabbit Ears after Intravenous Papain, and Prevention of Recovery by Cortisone. Journal of Experimental Medicine, 104, 245. Surgery,

VOL.

49 B,

NO.

3,

AUGUST

1967