J. Neurol. Neurosurg. Psychiat., 1958, 21, 12.

ISCHAEMIC AND POST-ISCHAEMIC NUMBNESS ANDPARAESTIESIAE

BY

P. W. NATHANFrom the Neurological Research Unit of the Medical Researchl Council, National Hospital,

Queen Square, London

During the last 10 years much interest has beentaken in the sensory and motor phenomena asso-ciated with the occlusion of the blood supply to anerve. As only a sphygmomanometer is needed tocarry out the experiment, it seems desirable for allphysicians to become acquainted with the distur-bances of sensation that ensue, for the experimentreproduces in a short time many of the subjectivesensory disturbances for which patients seek medicaladvice. When this simple method of investigation iscarried out on patients, it may bring out abnormali-ties in function that are too slight to be detected byother clinical methods. The results of investigatingcertain clinical conditions by occluding and releasingthe blood supply to the limbs have been publishedrecently. Gilliatt and Grahame Wilson (1953) usedthis procedure to establish the diagnosis of thecarpal-tunnel syndrome, and later Gilliatt (1955)showed that in patients with spinal cord lesions thetime to numbness following occlusion of the cir-culation provides a good indication of the progress ofthe condition. Poole (1956a) established the limitsof the normal by recording the duration and severityof ischaemic and post-ischaemic paraesthesiae in93 normal subjects; and he later reported the changesfound in these paraesthesiae in polyneuritis (1956b)and in motor neurone disease (1957).As a result of the work of Lewis, Pickering, and

Rothschild (1931), Lehmann (1937), Kugelberg(1944, 1948), Sinclair (1948), Merrington andNathan (1949), Kugelberg and Cobb (1951),Marshall (1952, 1953), and Cobb and Marshall(1954), it is now known that the following eventsoccur when the blood supply to a nerve or to a certainadequate length of nerve is occluded.A few minutes after the occlusion has started, the

nerve fibres of the A group become hyperexcitable.This increased excitability is sufficient to result inthe fibres firing off spontaneously. When thisspontaneous firing occurs in certain sensory fibresof the A group, tingling in the cutaneous distributionof the nerve is felt. As the period of occlusion of the

circulation is continued, the nerve fibres pass througha stage of normal excitability, and eventually after astage of decreased excitability reach a stage of com-plete inexcitability. When this stage is reached, thedigits feel numb or " dead "; at the same time thesmall muscles of the hand or foot become paralysed.In the upper limb this occurs about 25 minutes andin the lower limb about 30 minutes after the onsetof the occlusion. On restoration of the blood flow,the nerve rapidly regains its ability to conduct. Thefibres of the A group first pass through a stage ofincreased excitability, longer lasting and far moreintense than that occurring during the ischaemicperiod. At this stage the long motor and sensoryfibres of the A group fire off spontaneously. This ismanifested with regard to the motor fibres byfasciculation in the muscles supplied by the nerveand even by tetanus; with regard to the sensoryfibres spontaneous firing is manifested as paraes-thesiae. If at this stage the nerve is stimulatedelectrically, single impulses are transformed intodouble or multiple impulses. The work of Bazettand McGlone (1929, 1932) and of Merrington andNathan (1949) shows that the various forms ofparaesthesiae are related to the groups of fibressubserving various sensations, namely, the thermalparaesthesiae from discharges of the fibres sub-serving thermal sensation, tingling from dischargesof the fibres subserving touch, pricking from dis-charges of the fibres subserving pressure in the skin,and pseudo cramp from discharges of the afferentfibres from muscle. Ten to 15 minutes after anocclusion lasting 20 minutes the excitability of thefibres returns to normal; at this time the subject nolonger experiences any abnormalities in motor orsensory function. These changes in excitability aremore prominent in the large peripheral nerves(median, ulnar, sciatic) than in small nerves. Andit seems to be that the increased excitability is moremarked in the proximal than in the distal parts ofthe nerves. It is known that all the changes men-tioned occur in the nerves and not in the end-organs.

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ISCHAEMIC AND POST-ISCHAEMIC NUMBNESS AND PARAESTHESIAE

72 volt

o60

!1 24

l 12voltI O0

The tingling felt during ischaemia is called "ischae-mic tingling " and the paraesthesiae after restorationof the blood supply " post-ischaemic paraesthesiae".At the times when paraesthesiae occur, inter-

ference with the perception of exteroceptive stimulihas been noted. Kugelberg (1944) noticed that whenischaemic tingling is pronounced " the appreciationof touch with a piece of cotton-wool is evidentlydiminished." Gilliatt and Grahame Wilson (1954)found that during the periods of ischaemic and post-ischaemic paraesthesiae tactile stimuli applied to thearea supplied by the spontaneously dischargingnerves are not felt or the response is diminished. Afailure to appreciate cutaneous stimuli occurs atthe times when the nerve is in a state of increasedexcitability. It is apparent that an investigation ofthis phenomenon may throw light on the mechanismof disorders of sensation experienced by patientssuffering from a variety of disorders. The purposeof this paper is to report the results of an investiga-tion on the numbness that occurs when nerve fibresare in a state of increased excitability.

Methods of InvestigationStimuli of various kinds were applied at intervals of

one minute to the dorsal surface of the ultimate phalanxof the big toe, index, or little finger immediately proximalto the nail.The following methods of stimulation were used:

FIG. 1.-Circuit diagram of stimulator delivering a spark stimulus.

33K nx

Ls I I D IgnltionColl.

(1) von Frey hairs for tactile stimulation which weremade of nylon suture thread, and calibrated by beingweighed against a balance. The weight in grams at whichthe hair started to bend was divided by the radius of thehair in millimetres, this figure denoting the " strength "of the hair; (2) the Weber'sche Tastzirkel (usually calledin English, a two-point discriminator).For pain sensibility (3) weighted needles, and (4) a

modified version of the instrument designed by Bishop(1943) was made by Mr. H. B. Morton; the circuitdiagram is shown in Fig. 1. The stimulus applied by thisinstrument consists of a spark, the spark gap beingabout 1 mm. The primary winding of the ignition coilwas fed with a charge accumulated in a 0 5 microfaradcapacitor charged from the selected input voltagethrough a 33 kilo-ohm resistor. The switch was in theprimary circuit. The voltage used was 60 or 72 volts.The spark which this instrument gives was applied asfollows. A screw connected to the output was sunk in aperspex block, which fitted the terminal phalanx; it wasfixed on the digit by rubber bands. By raising or loweringthe screw, the size of the spark gap could be varied. Theadvantage of such a stimulator, as Bishop (1944) main-tained, is that the electrical stimulus is sharply localizedand of shorter duration than any mechanical stimulus;moreover, it causes no deformation of the skin. Appliedto the skin of the terminal phalanges, just proximal to thenail, this spark usually gives rise to a sensation of prickingpain. If, instead of this prick, either a slight tap or a painso slight that it was hardly painful was experienced, thenthe perspex application was moved a millimetre or so,

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P. W. NATHAN

until a place was found where stimulation gave a sharp,painful prick; this sensation was immediate and notdelayed. It was possible to show that the impulses setup by this form of stimulation were not transmitted inC fibres. On theoretical grounds alone, the rising timeof the spark stimulus is so short that it would be unlikelyto give rise to impulses in fibres having such good accom-modation as C fibres. It was readily shown, by occludingthe circulation to the limb, that the spark stimulus nolonger aroused a sensation when only C fibres remainconducting; indeed this stimulus ceased to arouse asensation before the von Frey hair ceased to do so. Thusit may be concluded that this instrument causes impulsesin fibres normally used for the sensation of prickingpain, but not the C fibres.

(5) The electrical stimulation devised by Dawson andreported by Dawson and Scott (1949) and Dawson (1956)was applied through ring electrodes around the fourthand fifth digits of the upper limb; it caused a sensationbest described as a slightly painful, heavy blow on thedigits.The stimuli, apart from that using the ring electrodes,

were applied in the following manner: The point lessthan 1 mm. diameter at which the stimulus was appliedwas marked in ink. The number of affirmative answersto 10 stimulations was noted at each minute. On mostoccasions all 10 stimuli were applied within the first30 seconds of the minute. Before each group of 10stimuli, the subject was warned by the words " Ready ?Now !" The rate of application of the stimuli wasrandom, a rhythm of stimulation being studiouslyavoided. It was found that provided the stimuli were notapplied too rapidly, hallucinations of touch were veryrare in most subjects; they did occur, however, whensensibility began to fail completely, after about 20 minutesof occlusion in the upper limb; each hallucination wasthen scored as a missed real stimulation. The von Freyhairs were applied in such a manner that the distancebetween the tip of the hair and the skin was about 1 cm.before the hair was lowered on to the skin; the hair waspressed on to the skin until the hair bent, and care wastaken to apply the hair on each occasion in as similar amanner as possible.The two-point discriminator was used with a distance

of 2 5 cm. between the points; the results were scored,in order to permit the graphic presentation, as follows:A = correct response with no difficulty in judging;B = doubtful response, with difficulty in judging;C = wrong response or complete inability to judge.

Vascular occlusion was obtained by using the ordinarysphygmomanometer cuff on the arm and a speciallydesigned wide cuff on the thigh. A standard position oneach limb was used: the cuff was placed on the thighwith its lower edge 4 to 5 cm. above the upper edge of thepatella, and on the arm with its lower edge 1 to 2 cm.above the medial epicondyle.The skin of the limb was kept at a nearly constant

temperature by placing the limb within the field ofradiation of heating lamps arranged in an inverted cradle.The skin temperature was monitored by means of athermojunction.

Electrical stimulation was used by means of the ring

electrodes. Records of the nerve action potentials throughthe skin were, with minor modifications, made in the waydescribed by Dawson and Scott (1949) and Dawson(1956). The compound action potential due to the ascend-ing volley was recorded at two places over the ulnarnerve by two pairs of electrodes: one pair was placeddistal to the sphygmomanometer cuff, just above thewrist, and the other pair proximal to the cuff, just abovethe elbow. An earth connexion was made to a place onthe flexor surface of the forearm. In order to obtainadequate relaxation so as to avoid obscuring the inducedaction potential by artifacts due to muscle actionpotentials, the subject lay on his back with his upperlimb supported on straps slung from a beam. Thestimulus on the digits applied by the ring electrodes gaverise to a single synchronous impulse, which, it is known,is conducted in large fibres.The experiments carried out on healthy subjects are

not all given in the paper; a typical one is chosen from aseries of similar experiments performed on at least 10healthy subjects. Experiment 8 is one of three similarexperiments.

Experimental FindingsThe phenomenon under investigation is best

shown by Experiment 1, illustrated diagrammaticallyin Fig. 2.

Experiment 1 (Fig. 2).-The stimulus was a von Freynylon hair No. 3, strength 1. Before the cuff was placedon the thigh, the subject, a healthy male aged 32, wasstimulated 50 times on the dorsum of the big toe, to becertain that the hair strength was above threshold. Theperiod of occlusion was 19 minutes.As can be seen from Fig. 2, during the phase of

ischaemic tingling, the ability to feel the stimulation wasvery slightly impaired. During the phase ofpost-ischaemicparaesthesiae, the temporal pattern of disturbance of theability to feel the stimulus of the hair was found. Withinhalf a minute of releasing the cuff, the stimuli were feltagain; in this experiment 7/10 were felt. Three-quartersof a minute after releasing the cuff, post-ischaemictingling and pricking started, at which time some of thestimulations were still causing a sensation. By the timethe post-ischaemic paraesthesiae were fully developedno stimuli with the hair could be felt. Three minutesafter releasing the cuff, the appreciation of the stimuliwas fully restored; the post-ischaemic paraesthesiae wereby this time diminishing, though some tingling remained.The temporary slight hypoaesthesia accompanying

the ischaemic tingling is not easily observed. If thestimulus is too strong, no diminution in the numberof correct responses is found; the stimulus strengthhas to be just threshold in the normal period. Thefailure to respond to the stimuli is not due to bore-dom or to lack of attention. If the experiment iscarried out again, omitting the application of thecuff, the subject continues to respond to allthe stimuli applied throughout every minute ofthe 22 occupied by the test.The failure to respond to the stimulation is more

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ISCHAEMIC AND POST-ISCHAEMIC NUMBNESS AND PARAESTHESIAE 15

FIG. 2.-Cuff on thigh. Stimulus, hair of strength 1. SEVERE TINGLING IAND PRICKING

TINItSLIGHTTINGLING

10'

9.8'

1w' 7*z 6-Q3 5.2 4.InPu. 3.

m 2-w

ZIlz

0-I I I .9 .I I .I .II I .I I I I .

6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16t MINUTES AFTER APPLICATION OF CUFF

CUFF APPLIED

definite during the period of post-ischaemicparaesthesiae; then, even the application of rela-tively heavy hairs evoked no response.Although this failure to feel exteroceptive stimu-

lation is only slight in the ischaemic phase amonghealthy people, in patients withpathological conditions of the ner-vous system this failure is morepronounced. Experiments on lopatients with very slight defects of

9sensibility show the inability to feel 9the stimulation in a marked formn 8An example is presented in the next

7

experiment.Experiment 2 (Fig. 3).-A similar

experiment to Experiment 1 wascarried out on a patient suffering frommeningo-vascular syphilis. In thispatient the threshold for touch sensi-bility was very slightly raised. Astimulus of a nylon No. 1 hair, weight0-05 g., was applied to the dorsum ofthe little finger just proximal to thenail; the cuff was in the standardposition. A diminution in the numberof correct responses occurred at thefirst minute and continued till the endof the sixth; this was concurrent withischaemic tingling. The diminutionin the response to stimulation

6-=5.403.

2a.

20*Z I.z

7 18 9 i 2 3t MINUTES AFTER

REMOVAL OFCUFF

CUFF REMOVED

was more intense than is found in healthy subjects.How the diminution in sensation is related to the

strength of the stimulus is shown in the next experi-ment, carried out on a healthy subject.Experiment 3 (Fig. 4).-Two strengths of stimulus were

|TINGLING FIG. 3.-Cuff on arm. Stimulus,hair of weight 0-05 g.

O 1 2 3 4 5 6 7 8 9 10 11 12 13MINUTES AFTER APPLICATION OF THE CUFF

CUfF APPUED

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P. W. NATHANHAIR OF STRENGTH 1.

------ HAIR OF WEIGHT O.05 G

I-w

z0

-i

2I-

0

w

z

i'I'I% I I

% I I

II I% ISI I

I

I . I I *1 I I I I I

0 2 4 6 8 K 12 14 16 iiMINUTES AFTER APPLICATION OF CUFF

CUFF APPLIED CUFF

applied to the left index of a healthy male aged 32:stimuli were nylon No. 1 and No. 3 hairs. Withnylon No. 3 hair, stimulation readily causes a sensatrecognized as an easily felt touch; with the nylon Nchair, the sensation is slight and needs the full attentof the subject for its appreciation. Stimulation was jproximal to the nail. Before the period of occlusiwhich lasted 19 minutes, the heavier hair was felt 50of 50 times and the lighter hair 46 out of 50 times.From Fig. 4 it can be seen that during the time

ischaemic tingling the heavier stimulus continued tofelt but the lighter was not felt on all occasions. Durthe period of maximal post-ischaemic paraesthesiae, thwas a period during which neither stimulus was felt;appreciation of the heavier stimulus returned before tof the lighter.

Three points are brought out by this experime(1) only a very light touch stimulus is blocked durithe ischaemic tingling; (2) in the post-ischaerphase the light touch stimulus may not be iimmediately after restoration of the circulationheavy stimulus may be felt fully and normawithin 15 minutes of restoration of the circulaticit is no longer felt, however, when paraesthesiae;at their height; (3) in the post-ischaemic period evslight paraesthesiae prevent the lightest stimbeing felt.The disturbance of sensibility is confined to

cutaneous distribution of the nerves involved by 1ischaemia. If, instead of a cuff occluding the cir

FIG. 4.-Cuff on arm. Stimuli, hairs lation to the whole limb,of strength 1 and of weight005 g. a clamp is applied to a

single nerve so as to ob-| TINGLING AND PRICKING struct its blood supply

over a distance of 5 cm.or more, then all thephenomena will be re-stricted to the distribu-tion of that nerve. If theulnar nerve is com-pressed, then ischaemicand post-ischaemic para-esthesiae will be felt onlywithin the cutaneous dis-tribution of that nerve.

a2LLl sThe touch stimuli ap-a/# plied to the two sides of

the fourth digit, one be-ing within the ulnar andthe other within themedian territory, give

'* * u* * l l rise to different experi-9 1 3 5 7 9 11 ences during the periods

MINUTES AFTER REMOVAL OF CUFfr\ ~~~~~ofparaesthesiae; allthose applied to that

REMOVED half of the digit suppliedby the median nerve

the continue to be felt, whereas a percentage of thosethe applied to the other half of the digit are missed.;on Though the two points stimulated be only I cm."ion apart, the subject is able to appreciate very lightjOst touches on the median half of the fourth digit whileust he experiences showers of paraesthesiae on the ulnarout half of the digit.

The next problem was to find out if this oblitera-of tion of sensation is limited to that provoked by verybe slight stimulation with nylon hairs. It was founding that the alteration of sensation is not merely limitedere to touch caused by the von Frey hairs. For, duringthe the post-ischaemic phase, the sensation induced byhat rubbing the fingers together feels altered, blurred,

or, in the words of most patients, it feels " numb ".nt: The following experiment also shows that there is aing disturbance of those forms of sensibility needed innic discriminating two points.Felt; ailly:)n;are{enluli

thethecu-

Experiment 4 (Fig. 5).-The cuff occluding the circula-tion was placed on the thigh of a healthy male aged 30.Two forms of stimuli were applied to the dorsum of thesecond digit, namely, a nylon No. 3 hair and the two-point discriminator with the points 2-5 cm. apart. It wasfound that during the ischaemic tingling the subject wasunable to feel all the stimuli with the von Frey hair andwas unable also to discriminate the two points withcertainty.

It may thus be concluded that heavier touch sensi-bility is also obliterated during the time of the

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ISCHAEMIC AND POST-ISCHAEMIC NUMBNESS AND PARAESTHESIAE

paraesthesiae. This was alsoshown on innumerable occa-sions when heavier von Freyhairs were used. Althoughthe subjects continued to feelall such stimuli, they noticedthat the sensation arousedwas less distinct during thetimes of paraesthesiae.

It was decided next to findout if during the periods ofparaesthesiae there is altera-tion in the threshold forpainful stimuli.Experiment 5 (Fig. 6).-The

stimulus was the " sparker"mentioned under " Methods".The voltage was 60; the perspexapplicator was fixed on the tipof the big toe of a healthy maleaged 40. The pressure in thecuff was kept raised for 13minutes. The number of stimulifelt is plotted in Fig. 6. How-ever, in experiments where apainful stimulus is used, it ismore important to record thesensations of the subject. Thesubject reported as follows:At 3 min., "The stimulus

feels about half as strong aspreviously."

FIG. 6.-Cuff on thigh. Stimulus,sparker, voltage 60.

10-

9-

8-1Aw 7.1. I

z 6-04 5.iS-I2 4-

3.0t 2-Ul

I.z

0-

A]B-

C-

U.

u4

0

2u.4

FIG. 5.-Cuff on thigh. Stimuli, hair ofstrength 1, and two-point discrimin-

TINGLING ator, the points at 2-5 cm. apart. Inthe scoring, A = correct response, with

easy discrimination. B =doubtfulresponse, with difficulty in dis-

crimination. C = wrongresponse, with complete

ility to discriminate.

O 1 .2 3 4 5 6 7 8 9 10 11 12 13 14 15MINUTES AFTER APPLICATION OF THE CUFF

CUFF APPLIED

TINGLING TINGLING AND PRICKING

O 1 2 3 4 5 6 7 8 9 10 11 12 13 1 2 3 4 s 6 7 8 9MINUTES AFTER APPLICATION OF CUFF MINUTES AFTER REMOVAL OF CUFF

CUFF APPLIED CUFF REMOVED

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P. W. NATHAN

At 5 min., " It is still very weak." The two stimulationsthat were not felt caused no sensation of any kind.At 6 min., They are quite unlike the original pricks."At 7 min., " Now they feel the same as they did

originally."At 8 min., They are exactly the same as they were

originally."At 9 min., The stimuli are slightly weaker, but they

are still painful pricks."At 10 min., " Very weak, but still painful pricks."At 11 min., three stimuli caused no sensation.During the post-ischaemic phase, all the stimuli were

felt half a minute after release of the cuff; of these, thefirst five seemed to the subject to be about half the fullstrength, the second five of full strength. Then, untilfive minutes after release of the cuff, no stimuli were felt;nine minutes after release, although the stimuli were felt,the sensation aroused was still about half normal.

It will be seen that the plotted curve closelyresembles the curves obtained when a light touchstimulus is used. A difference is that the inabilityto feel the painful stimulus during the post-ischaemicphase lasted a long time, as did the paraesthesiae.

It is not always possible to discriminate objectivelyan alteration in sensation when subjectively thealteration may be marked; this is especially likelywhen the sensation is that ofpricking pain. Although,in the next experiment, 10 out of 10 stimuli fromthe " sparker " continued to be felt as pricking painthroughout the period of ischaemia, the quality ofthe sensation changed. This change in qualityoccurred at a time when in some subjects a quantita-tive change was demonstrable.Experiment 6.-The input voltage of the " sparker"

was 72. The cuff was placed on the thigh of a healthymale aged 32. The stimuli were applied to the dorsumof the second digit. The subject reported as follows:At 3 min., "Some of the sting has gone out of the

pricks."At 4 min., "It feels the same; some of the sting has

gone."At 5 min., "Not all the stimuli have the same inten-

sity."At 6 min., " They feel definitely duller."At 7 min., " Now they all feel sharper. They feel about

the same as they did before the cuff was put on."At 8 min., " Very slightly duller; but not as dull as

they were earlier on, at about three minutes."At 10 min., " Duller, less sharp in quality."At 11 min., " Toes are slightly numb when rubbed."At 12 min., " This numbness is definite. Now some

of the spark stimuli are quite definitely not pricking atall; they have become touches."Half a minute after release of cuff, nine stimuli were

felt as touch, one as prick.One and a half minutes after release, the paraesthesiae

are marked. " I cannot really tell if the stimuli are likepricks or touches."At 2 min. after release, two stimuli felt as touch, eight

not felt at all.

At 3 min. after release, two stimuli felt as very slightpricks, eight felt as touch.At 5 min. after release, all 10 felt as the same pricking

sensation as at the beginning of the experiment.This experiment illustrates the fact that, when all

the stimulations arouse a sensation, during theperiods of paraesthesiae the quality and intensityparticularly of the sensation is altered.

Also within the modality of pain, the heavier oftwo stimuli may be felt at the time of the paraesthe-siae, while the lighter is not. This is illustrated in thefollowing experiment.

Experiment 7 (Fig. 7).-The stimuli were pins weightedwith 5 and 20 g. The cuff was on the thigh of a healthymale, aged 36, for 22 minutes. The results for the periodafter release of the cuff are shown in Fig. 7. There is theusual obliteration of sensation during the period ofintense paraesthesiae; the responses to stimulation withthe 5 g. pin are lost far longer than those with the 20 g.pin.

All the experiments reported so far have beenrepeated, using a clamp to occlude the circulationonly to a certain length of a single nerve. All thephenomena described above occurred, though thechanges were of a slighter degree. It may thereforebe concluded that the alteration of the sensationsof light touch, of heavy touch or skin pressure,and of pricking pain, are not the result of ischaemia

-PIN WEIGHTED AT 20G.-----PIN WEIGHTED AT 5G.

TINGLING AND PRICKING

10/

WI 2

z R

0I 2 3 7MINTESAFER EMOALOf UF

CUFFREMOVED~~~~~

FIG. 7.-Cuff on thigh. Stimuli, pins weighted at 5 and 20 g.

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ISCHAEMIC AND POST-ISCHAEMIC NUMBNESS AND PARAESTHESIAE

of the end-organs* but of the nerve itself.In considering the mechanism causing the raising

of the threshold, it is unlikely that it is due to aninability of the nerve fibres to conduct impulses, forthe period of ischaemic tingling is followed by aperiod of perfect conduction during which all stimuliare felt. Again, during the post-ischaemic phase,on release of the vascular occlusion, all or almostall of the stimuli are felt, showing an apparentrecovery of the nerve's ability to conduct, and yet afew seconds later, when recovery would be thoughtto have progressed, the threshold to stimulation israised again.Two different explanations of this raised threshold

to sensory stimulation may be considered. Oneexplanation offered is that the impulses caused bythe test stimulus cause insignificant effects withinthe central nervous system already bombarded by a

*The term " end-organ " is used not to imply any histologicallydemonstrable structure. Physiologically there is reason to believethat the termination of a nerve (the receptive element) has specialproperties, different at least quantitatively from those of the nerveitself (the conducting element). The term is used here to mean thisphysiological aspect of the receptive element.

profusion of impulses arriving from the nerve whichis discharging spontaneously. This overwhelmingof the signal could be occurring at some level in thecentral nervous system, yet it need not be conceivedas necessarily involving consciousness. Anotherexplanation offered is that the impulses caused bythe test stimulus travelling orthodromically areblocked by antidromic impulses arising spontaneous-ly within the nerve fibres in the region of ischaemia.These two groups of impulses travelling towardseach other from opposite ends of the fibre couldextinguish each other. Whether the impulses due toperipheral stimulation would get through to thecentral nervous system or not would depend on thenumber generated in a unit of time and the numberof spontaneous impulses generated; eventually someperipherally arising impulses would get through theregion of spontaneously firing impulses, if the formerare arising faster; and conversely, if they arise lessfrequently than those generated spontaneously inthe hyperexcitable nerve fibres, then they would beobliterated before they reached the central nervoussystem.

I iojiv

A B C D

FIG. 8a.-Superimposed tracings of the action potentials produced by stimulating the fourth and fifth digits recorded over the ulnarnerve at two places. The upper tracing shows the centripetal volley recorded at electrodes 3 and 4, and the lower tracing the volleyrecorded at electrodes 5 and 6. The time scales show I and 5 milliseconds. In the diagram of the upper limb, electrodes 1 and 2are ring electrodes used for stimulation, 3 and 4 are the electrodes over the ulnar nerve distal to the cuff, and 5 and 6 are the electrodesover the ulnar nerve proximal to the cuff. An earth connexion was made at the plate placed on the forearm at E. Records A, B, C,and D were taken respectively before the cuff was applied, five minutes and 25 minutes after the cuff was applied, and 2-5 minutesafter release of the cuff.

19

A v v v v , I ImowfIt

io,uvs Al-

r. .I r6 e

I A v v 9 I , 0 I pmpmt f-I v v 0 , I I

I

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P. W. NATHANFIG. 8b.-The heights of the waves of the action potentials distal and proximal to the cuff are plotted, and also the ratio of the proximal

to the distal height, expressed as a percentage.

HEIGHT OF PROXIMAL ACTION POTENTIAL EXPRESSED AS A PERCENTAGE OFHEIGHT OF DISTAL ACTION POTENTIAL TINGLINPAND PRKKING

_ HEIGHT OF WAVE OF PROXIMAL ACTION POTENTIALHEIGHT OF WAVE OF DISTAL ACTION POTENTIAL STIMULUS STIMULUS

STIMULUS TIME TO STIMULUS NOT SLIGHTLY STIMULUSFEELS WEAKER NUMBNESS NOT FELT FELT STRONGER NORMAL

STIMULUS| STIMUWSIFET JUST

FELT

1W.1-1~~~'i

1..

~~ e_.s~~~% I0

/.. 0 0

/

/

/.

I I IIII I I I I I 11I I I I I I lI

2 4 6 8 10 12 14 16 18 20 22 24 26 2Y2 4Y2 68/2 Ol 101/2 12Y2MINUTES AFTER APPLICATION OF CUFF MINUTES AFTER REMOVAL OF CUFF

CUFF APPLIED CUFF REMOVED

Thus, the question to be decided is whether thenormal pattern of impulses needed for sensation failsto arrive at the central nervous system owing tobeing blocked in the peripheral nerve, or whetherthis normal pattern does arrive and is disturbedwithin the central nervous system owing to theconcomitant arrival of impulses spontaneouslygenerated in the same nerve.

Experiments were performed to find out if theimpulses derived from electrical stimulation werearriving at the central nervous system and yet werenot giving rise to sensation at a time when paraes-thesiae were being experienced. The followingexperiment was carried out with the help of Dr.G. D. Dawson and Dr. R. W. Gilliatt, the latteron this occasion being the subject.

Experiment 8 (Figs. 8a and 8b).-The arrangement of

electrodes has been described in the section on "Methods";it is illustrated in Fig. 8a. The action potentials producedby stimulating the fourth and fifth digits were recordeddistal and proximal to the cuff, placed over the elbow.In Fig. 8b are plotted the heights of the proximal anddistal action potentials, expressed as a percentage. Duringthe early post-ischaemic period, at 2-5 minutes afterrelease of the circulation to the limb, the subject wasunable to feel the stimulus; in fact, in this actual experi-ment, he asked Dr. Dawson to look at the stimulatingelectrodes, as he felt sure that they must have slipped off.At this time it can be seen from Fig. 8a (D) that therewas a large action potential proximal to the cuff. It maythen be concluded that the impulses were passing intothe central nervous system. This inability to feel thestimulus occurred at a time when the size of the com-pound action potential proximal to the cuff was 75% ofthat distal to the cuff. During the ischaemic phase, whenthe compound action potential proximal to the cuff was

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75% to 80% of that distal to thecuff, the stimulus had been clearlyfelt; and it had been felt evenwhen the proximal action poten-tial was too small to be recorded.Further, within the first half-minute of restoration of the cir-culation, before the paraesthesiaehad begun, the stimulus was felt;and at this stage the size of theaction potential both distal andproximal to the cuff was less thanwhat it was later, when thestimulus causing this actionpotential failed to give rise to anysensation.

FIG. 9.-Cuff on arm. Stimulus, hair of strength 1.

a.

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This and other similar ex-

periments show that whenparaesthesiae are severe, strongstimulation within the cuta-neous distribution of a nerve Vwdoes not arouse a conscioussensation, although the volley CUFF APPLIEdue to this stimulation canbe shown to pass along the nerve towards thecentral nervous system. Thus, of the two hypothesesproposed, the evidence suggests that the one is truewhich states that there is a disturbance in the centralnervous system which gives rise to the failure to feelthe test stimulus. Experiments such as Experiment8 also show that, during the periods of spontaneousgeneration of impulses, the whole nerve is capable ofconducting single synchronous volleys. While thisholds true for electrical stimulation, it would appearto be justified to suppose that the same applies to theimpulses set up by stimulation with more naturalforms of stimuli, as with a hair, with the two-pointdiscriminator, and with a needle.That the masking of sensations arising in the

periphery is caused by some central disturbancemight also be deduced from two of the experimentsreported above, namely, Experiments 6 and 7. Inthese experiments, during the post-ischaemic para-esthesiae the sensation of pain was not aroused whenappropriate stimulation was applied. It is knownthat the nerve fibres concerned in the mediationof pain sensibility do not discharge spontaneouslyduring the post-ischaemic period. Thus a peripheralmechanism does not account for the obliteration ofsensation also in these two experiments.The impulses arising spontaneously do not have

to arouse a conscious sensation before obliterationof the sensation aroused by peripheral stimulationtakes place. This is seen when an experiment iscarried out on the lower limb; often in this limb noischaemic tingling is experienced. At the time whensuch paraesthesiae occur in the upper limb, namely,

2 3 4 5 6 7 8 9 10 I1 12MINUTES AFTER APPLICATION OF CUFF

ED CUFF

13

REMOVED

about one to three minutes after occlusion of thecirculation, there is in the lower limb the usualinability to feel light touches. Thus, this sensation ismasked, even though no paraesthesiae are being felt.The same thing can occur with certain lesions affect-ing sensory pathways in the central nervous system.This is shown, for instance, by the followingcase.

Experiment 9 (Fig. 9).-Mr. W. suffered from athrombosis of the left posterior inferior cerebellar artery.In addition to the loss of thermal and painful sensibilityon the right side of the body, there was a very slightabnormality of tactile sensibility of the left upper limb.This was sufficient to prevent the sensation of ischaemictingling, for slight lesions of the tactile pathway preventthe appearance of ischaemic tingling.The stimulus was the nylon No. 3 hair, strength 1,

applied to the left index finger, just proximal to the nail.Fifty applications were felt before the cuff was appliedin the standard position. Although there was no ischae-mic tingling, there was diminution in the number ofresponses to touch occurring at the time when ischaemictingling is usually experienced (see Fig. 9).

In this patient interruption of the sensory pathwaywas within the medulla oblongata; it is probablethat the lesion at this level was the cause of hisfailure to experience ischaemic tingling. Though inthis patient the impulses usually causing tinglingapparently did not enter consciousness, nevertheless,they could produce an effect which obscured thesensation due to the test stimulation. This effectpresumably was not being caused below the lesionin the medulla oblongata.

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P. W. NATHAN

DiscussionIt is usually considered that numbness results

from a diminution in the number of conductingfibres. However, following the work of Gilliatt andWilson and that reported here, it is apparent thatnumbness may also accompany an increased ex-citability of the larger nerve fibres. It may be dueto such fibres spontaneously firing off impulses intothe central nervous system; the reception of theseimpulses impairs the perception of peripheralstimulation, and this can occur even though thespontaneously arising impulses are giving rise to nosensation. Thus, numbness can be due to an inade-quate number of conducting fibres; it can also bedue to a large number of fibres firing off sponta-neously when they are in a hyperexcitable state. Nodoubt this kind of numbness occurs under abnormalbiochemical conditions. The changes occurring soonafter the onset of vascular occlusion and very soonafter the release from that occlusion are known tobe the same as those produced by an increase in pHor a decrease in calcium ion concentration. Robinson(1955) has studied sensation in patients with tetany.He found that when a cuff is placed on the upperlimbs of these patients numbness occurs twiceduring the period of occlusion; first it occurs atthe time of ischaemic tingling, which is marked insuch cases, and second when the nerve fibres ceaseto conduct, which they do after very short periodsof occlusion of the circulation.

It has always seemed curious to me how patientstend to use the terms " numb " and " tingling"indiscriminately. That there is a reduced ability tofeel peripheral, stimulation during periods ofparaesthesiae is now clear, and the more marked theparaesthesiae, the more definite the disturbance ofperipheral sensation will be.

This is not to imply that all numbness is associatedwith tingling; in fact, much of the numbness ofpathological conditions is similar to the velvetynumbness that occurs after 20 minutes or so of anoccluding cuff on the limb of normal subjects; thisform of numbness is due to the failure to conductof large numbers of the fibres.The occurrence of these central factors in the

obscuring of sensation must not lead one to accountfor all of the sensations associated with the periodsof paraesthesiae as being due to central events.Many of these phenomena are most easily accountedfor on the basis of an interaction in the peripheralnerves between orthodromic impulses and spon-

taneously arising antidromic and orthodromicimpulses. For instance, during the period of post-ischaemic paraesthesiae, there may be a short periodduring which each adequate stimulation with a haircauses a feeling like a buzz continuing till the next

application of the stimulus. This is most easilyexplained on the basis of reiterative firing and pro-longed after-discharge during a phase of greatlyincreased excitability. When excitability is furtherincreased, then each peripheral stimulus will causea little volley of paraesthesiae; it is likely that theimpulses due to peripheral stimulation, on reachingthe region of spontaneous firing of impulses, set offgroups of reiteratively firing impulses; thus theyincrease the spontaneous discharge. This is probablythe explanation of the well-known fact that pins andneedles can be increased by rubbing or pressing uponthe part in which they are felt. A similar explanationprobably underlies the fact that just before paraes-thesiae appear spontaneously, they can be inducedby rubbing or pressing the parts in which they areabout to be felt.

It is surprising to find from experiments such asExperiment 8 that single synchronous volleys canget through to the central nervous system, and,under certain circumstances, give rise to no sensa-tion. It is even more surprising to anyone who hasfelt the stimulus used for it is only just bearable;if it were made stronger, it would be impossible torelax the limb. If such a massive stimulus can beobliterated during the period of post-ischaemicparaesthesiae, it is likely that the same occurs forlighter and more usual kinds of stimulation.Normal sensation depends on more complicated

events than those arranged in Experiment 8. Sucha single volley derived from a short stimulus, appliedmidway on the course of a nerve through the skin,is an artificial affair, and unlike the natural stimula-tion from everyday stimuli applied to end-organs.Impulses, in fact, are never single but come inbattalions; trains of impulses are set off when thestimulus is applied and trains are set off when thestimulus is removed, and both are followed by anafter-discharge. To alter sensation, it may be enoughto alter the after-discharge or it may be enough toprolong the relatively refractory period of somefibres, so that alternate impulses, for instance, do notget through. It is unknown how much interferencewith the normal pattern of impulses arriving at theneurological substratum of sensation can be toleratedwithout there being an interference with normalsensation.

SummaryDuring the periods of ischaemic and post-ischae-

mic paraesthesiae, stimuli applied to the territoryof the nerve spontaneously discharging are eithernot felt or they are felt in a diminisheddegree.

This interference with the perception of stimuliis enough to cause a real disturbance of sensation,

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and it is described as "numbness" by thoseexperiencing it.The forms of sensibility obliterated during these

periods are touch, pressure, and pain. (Thermalsensations have not been investigated.)

It was found that this " numbness " is not due to afailure of the impulses to reach the central nervoussystem; it is, therefore, due to some process takingplace within the central nervous system.

It is concluded that numbness is not only due to alarge number of fibres ceasing to conduct impulses,but it can also be due to fibres being hyperexcitableand firing off spontaneously; in such a case peri-pheral stimulation is not felt.

I take this opportunity of thanking Dr. George Dawsonand Dr. Roger Gilliatt who performed a great many ofthe experiments with me and helped throughout byuseful discussions, and Dr. E. Arnold Carmichael for his

interest and the opportunities he provided for doingthis work.

REFERENCESBazett, H. C., and McGlone, B. (1929). Amer. J. Physiol., 90, 278.

(1932). Arch. Neurol. Psychiat. (Chicago), 28, 71.Bishop, G. H. (1943). J. Neurophysiol., 6, 361.

(1944). Ibid., 7, 71 and 185.Cobb, W., and Marshall, J. (1954). J. Neurol. Neurosurg. Psychiat..

17, 183.Dawson, G. D. (1956). J. Physiol., (Lond.), 131, 436.

, and Scott, J. M. (1949). J. Neurol. Neurosurg. Psychiat., 12.259.

Gilliatt, R. W. (1955). Ibid., 18, 145.and Wilson, T. G. (1953). Lancet, 2, 595.

(1954). J. Neurol. Neurosurg. Psychiat., 17, 104.Kugelberg, E. (1944). Acta physiol. scand., 8, Suppi. 24.

(1948). Arch. Neurol. Psychiat. (Chicago), 60, 140.and Cobb, W. (1951). J. Neurol. Neurosurg. Psychiat., 14, 88.

Lehmann, J. E. (1937). Amer. J. Physiol., 119, 111.Lewis, T., Pickering, G. W., and Rothschild, P. (1931). Heart. 16, 1.Marshall, J. (1952). J. Neurol. Neurosurg. Psychiat., 15, 242.

(1953). Ibid., 16, 19.Merrington, W. R., and Nathan, P. W. (1949). Ibid.. 12. 1.

Poole, E. W. (1956a). Ibid., 19, 148.(1956b). Ibid., 19, 281.

-(1957). Ibid., 20, 225.Robinson, P. K. (1955). Neurology, 5, 461.Sinclair, D. C. (1948). J. Neurophysiol., 11, 75.

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