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Figure 6-1. A cross section through the cervical

spinal cord showing the entry of the two divisions

of the dorsal roots and the routes that fibers take

into the major ascending tracts. (C rosby EC,

Humphrey T, Lauer, EW : Correlative Anatomy of

the Nervous System . New York, Macmillan, 1962)

CHAPTER 6

SOMESTHESIA - CENTRAL MECHANISMS

In this chapter, we will examine thepathways that somatic activity can takein the central nervous system, and then

we will consider the mechanisms by whichdifferent sensations can occur.

Somatosensory pathways.Once the primary afferent fibers leave

the skin, they group together into larger andlarger bundles in the cutaneous nerves. Atsome point in their course they are joined bymuscle nerves, containing sensory and motorfibers of the muscles. Nerves that innervatethe skin are termed cutaneous nerves, andthose that contain both skin and musclefibers are termed mixed nerves. The sciaticnerve is an example of a mixed nerve. Nerve fibers that carry impulses to the CNSare called afferent; those that carry themfrom the CNS are efferent. The afferentand efferent fibers are separate from eachother at the skin or muscle, but they areusually mixed together along most of thecourse of the nerve on the periphery. Nearthe spinal cord, the afferent and efferentfibers separate again, the efferent fibersgoing to the ventral (or anterior) roots andthe afferent fibers, after passing their cellbodies in the dorsal root ganglia, goingthrough the dorsal (or posterior) roots. Thisseparation of afferent fibers in the dorsalroot and efferent fibers in the ventral root isthe so-called Bell-Magendie Law. Latelythis concept of a rigid separation of dorsal,sensory and ventral, motor fibers has beenchallenged by findings that, in the cat, up to30% of the ventral root fibers are sensory. This probably would not have surprised

Magendie, who originally stated that mostfibers in the ventral roots were motor.

The dorsal roots are often divided into twoparts, a lateral division consisting mainly ofunmyelinated fibers and a medial divisionconsisting mainly of larger, myelinatedfibers (see Fig. 6-1). Upon entering thespinal cord, some of the afferent fibersbifurcate, with one collateral descendingtoward the caudal regions of the cord and theother ascending toward the rostral regions. Both myelinated and unmyelinated fibersbranch extensively and have terminals nearthe dorsal root entry zone. The collaterals ofthe unmyelinated fibers go only a shortdistance, one or two segments, before

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Figure 6-2. The course and major relay points of

the dorsal column system. (Crosby EC, Humphrey

T, Lauer, EW : Correlative Anatomy of the Nervous

System. New York, Macmillan, 1962)

terminating in the dorsal horn, but a fibermay put down several collateral branchesthat terminate in many places in the graymatter. Descending branches of themyelinated fibers generally terminate withinone segment from their entry; however,many of the ascending branches can traveluninterrupted for long distances in the dorsalwhite matter, the dorsal columns, even

reaching the lower medullary levels wherethey terminate in the dorsal column nuclei,the nuclei gracilis (lower limb) and cuneatus(upper limb).

In the dorsal column nuclei, these fibersform connections with cells that live within

the nuclei themselves. As illustrated inFigure 6-2, the axons of these second-orderneurons immediately cross over to the otherside (decussate) of the brain stem, forming abundle of fibers, called the mediallemniscus. They are soon joined by fibers ofthe trigeminal system, serving the face, andalso by fibers from the spinothalamic tract.Those fibers that send a branch into the

dorsal columns at the segment of entry alsosend branches down into the gray matter. There they join the branches of othermyelinated fibers and unmyelinated fibers toparticipate in reflexes and other spinal cordactivities. Some of these fibers terminate oncells of the gray matter (second order cells),the axons of which cross in the anteriorcommissure to the contralateral ventralgray columns at or near the segment of entryand proceed into the ventrolateral whitecolumns. In this position, they ascend thespinal cord as the spinothalamic tract, untilthey join the fibers of the already decussatedmedial lemniscus in the brain stem. It iswrong to think of the spinothalamic tract,and perhaps any other central nerve tract, asbeing a compact bundle of fibers all ofwhich have the same origin, destination andfunction. In fact, within the region occupiedby the spinothalamic tract there are axons ofmany other ascending and descending tracts,making it virtually impossible to transectspinothalamic fibers and only spinothalamictract fibers.Primary afferent fibers from the region of

the face in front of the ears group togetherinto the trigeminal nerve and have their cellbodies in the semilunar ganglion. From thesemilunar ganglion the fibers enter the brainstem as a part of the fifth cranial nerve. Asin the spinal cord, many of the sensory fibersbifurcate immediately upon entering thebrain stem, sending an ascending branch to

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the main sensory nucleus of the trigeminaland a descending branch to the nucleus ofthe spinal tract of the trigeminal, a structureanalogous with the dorsal aspect of thespinal cord gray matter. Though most of thefibers arising from the second order neuronsof the trigeminal spinal nuclei decussate inthe brain stem and soon join the mediallemniscus, a few do not cross, but join theipsilateral medial lemniscus.

The fibers of the medial lemniscus,along with those from the trigeminal nucleiand the spinothalamic tract, proceed directlyto the ventral part of the thalamus,contralateral to the primary afferent fibersassociated with them. Fibers originating inthe main sensory nucleus and the rostralparts of the spinal nucleus of the trigeminalterminate in the nucleus ventralisposteromedialis (VPM) of the thalamus,whereas those of the caudal part of thespinal nucleus terminate in the intralaminarnuclei and the medial geniculate, and a fewend in VPM. Fibers originating in the dorsalcolumn nuclei and most fibers of thespinothalamic tract terminate in the nucleusventralis posterolateralis (VPL) of thethalamus. Some spinothalamic fibersterminate outside of VPL, notably in themedial geniculate body and suprageniculatenucleus.

The third-order fibers arising from thethalamic nuclei can then be traced outthrough the internal capsule to the somaticsensory cerebral cortex. In man, the primarysomesthetic cortex is the region of thepostcentral gyrus, the region immediatelyposterior to the central sulcus, from theSylvian sulcus to a place within themidsagittal sulcus.

There are other pathways that carrysomatic information and other areas of thecortex that receive it, but they play a more

subtle and less well-understood role insensation, and consequently there is less wecan say about them.It has been customary to think of the dorsal

column-medial lemniscus pathway as themediator of touch, pressure, vibratory(pallesthesia), and joint position senses. The spinothalamic tract was usually thoughtto carry information about pain, deeppressure, temperature, and crude touch. Thedifference between the information in thetwo pathways was thought to be thesensitivity or threshold (the dorsal columnsbeing more sensitive) and thediscriminability of the spatial qualities of thestimulus (the ability to locate the site ofstimulus being much greater for the dorsalcolumns). In the trigeminal system, thecaudal part of the spinal nucleus (somepeople still maintain the whole spinalnucleus) was thought to carry informationfor pain, temperature and perhaps also crudetouch, whereas the main sensory nucleuswas thought to relay information from theface about touch, pressure and vibration.There is an increasing body of evidence

that has cast doubt on the dichotomy offunction of the systems outlined above. Some of the evidence comes from laboratoryexperiments. When recordings were madeof the discharges of single identifiedspinothalamic tract cells, it was found thatsome of them did, in fact, respond tonoxious or thermal stimuli, in much thesame way as nociceptors or thermoreceptorsdiscussed ln the last chapter. In the monkey,these made up 30% of the fibers studied. Other fibers responded to light touch,pressure, or hair movement, in much thesame manner as the mechanoreceptive fibersfound in the dorsal columns. These made up40-60% of those fibers studied. Mostspinothalamic tract fibers (60%) responded

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to both light tactile stimulation and noxiousstimulation (Trevino DL, Coulter JD, MaunzRA, Willis WD: Localization andfunctional properties of spinothalamic cellsin the monkey. In Bonica JJ (ed): Advancesin Neurology, Vol. 4 Pain. New York,Raven Press, 1974).

Conversely, some dorsal column fibersrespond to stimulation that is franklynoxious. These fibers are located primarilydeep within the columns and are second-order, rather than primary afferent neurons. These second-order neurons make up 10-30% of the dorsal column fibers by someestimates, and are comprised of fibers thatrespond to light tactile as well as noxiousstimulation (77%), noxious stimulation only(6%), and light tactile stimulation (17%)(Angaut-Petit D: Exp Brain Res 22:471-493, 1975). There appears to be somediscrepancy between the responsiveness ofsingle fibers and the roles normally attri-buted to the tracts that contain them. Thesame sort of mixture of nociceptive andtactile responses has also been found in themain and spinal trigeminal nuclei. Thus, thesupposedly complete segregation ofsubmodalities in the different pathways doesnot hold up to physiological testing. Moreover, at least 3 other major ascendingpathways have been shown in animal studiesto carry both tactile and nociceptiveinformation.

Finally, cells that could be responsiblefor signaling the position of a joint, themuscle and perhaps joint receptors, do notform a part of the dorsal column-mediallemniscal system (Clark FJ: J Neurobiol3:101-110, 1972). The original datasuggesting the dorsal columns carry jointposition information came from patientswith tabes dorsalis, a syphilitic infectionwhich causes degeneration of dorsal column

fibers, but tabes dorsalis is a dorsal rootdisease and more than just dorsal columnfibers are affected.Additional evidence that casts doubt on the

dorsal column-spinothalamic dichotomycomes from the clinical literature. Becausethe spinothalamic tract and the dorsalcolumns serving one side of the body are ondifferent sides of the spinal cord and becausethe dorsal columns are on the dorsal aspectand the spinothalamic tract is on the moreventral aspect of the cord, it is possible totransect one without cutting the other1. Insome patients with intractable pain, pain thatis not diminished by drug treatment or evenby cutting the dorsal roots (dorsalrhizotomy), the spinothalamic tract was cut(spinothalamic tractotomy) at theappropriate level on the side opposite thelocation of the pain. These patients usuallyreceived immediate relief from the pain aspredicted, but there were two problems: (1)pain eventually returned in patients thatsurvived longer than 6 months, and (2) therewas a reduction in tactile sensitivity(hypesthesia) as well as pain (hypalgesia)and temperature sensitivity on the oppositeside of the body. These observations, not often made

because tractotomies are seldom performedon patients who are not terminally ill, do notexactly fit the dichotomy of functionbetween the two ascending systems. Likewise, surgical lesions of the dorsalcolumns in animals may result in little or nopermanent tactile loss and little analgesiceffect. When the dorsolateral columns areincluded in the lesion, there is a temporary

1 Dorsal column fibers are spatiallydistant from spinothalamic tract fibers, butfibers in other tracts may well be cut with aspinothalamic tractotomy.

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Knowledge of dermatomes is useful indiagnosis of some neurological as wellas non-neurological disorders.

analgesia with gradual recovery of painsensation. Ventrolateral column lesions(including the spinothalamic tract) are evenless effective in producing analgesia. Inman, lesions of the dorsal columns producerelief from phantom limb pain, but painreturns in several months. The same is truefor various sorts of pain and ventrolateralcordotomy. We will have more to say aboutthis problem later.

On the other hand, damage to half of thespinal cord in man leads to ipsilateralparalysis of voluntary (as opposed to reflex)movements, loss or reduction of touch andjoint sensation ipsilaterally, and loss oftemperature and pain sensationcontralaterally, the Brown-SequardSyndrome. This is as predicted from theclassical notion of dorsal column andspinothalamic tract function, but rememberthat there are other tracts within half of thespinal cord. At this point, the classicalnotion of the function of the spinothalamictract and the dorsal columns is still widelyaccepted. However, the wise student shouldexpect this notion to be revised before toolong and sensory transmission to beattributed to multiple tracts.Dermatomes and somatotopic organization

Fibers serving particular areas of skingather together to form nerves, and the areaserved by the different cutaneous nerves canactually be mapped. Such a map is shown inlateral parts of Figure 6-3. Each area is thecombination of the receptive fields of all thefibers in that nerve, i.e., it is the receptivefield of that nerve. Despite some variationfrom person to person, the receptive fields ofnerves are constant enough in location andextent to be clinically useful.

When a peripheral nerve is cut, the resultis an area of complete lack of sensation oranesthesia. The region is called the

autonomous zone and corresponds to thearea in the central part of a nerve's receptivefield. Only a part of the total field isanesthetic, as a natural consequence of theoverlap of receptive fields of neighboringperipheral nerves. Surrounding theinsentient autonomous zone is anintermediate zone in which there is partialsensation. Sometimes the overlap is soextensive that the loss of a small nerve ishardly noticed.The receptive fields of the fibers in a dorsal

root, when combined also cover a fixed,distinct area, the dermatome ("slice ofskin"). The dermatome of each dorsal rootis illustrated in Figure 6-4. Dermatomalorganization is a constant feature of thenervous system. Dermatomes overlap in thesame way that the receptive fields of bothnerves and single fibers do. There is,however, a region in each dermatome that isnot overlapped by adjacent dermatomes. Inthe case of a transected root, one shouldexpect to see hypesthesia in the regionsindicated in the central part of Figure 6-3. This sort of map is made by tracing areas ofhypalgesia following rupture ofintervertebral disks. Note thatcorresponding areas are smaller than thedermatomes of Figure 6-4. Again, theoverlap of adjacent dermatomes may be sogreat that a deficit is hardly noticed unlesstwo or more dermatomes are denervated! This is especially true of thoracicdermatomes for which there may be little orno nonoverlapped region.

The nerves serving adjacent areas of skin

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do not necessarily enter through the same oreven adjacent dorsal roots. This isespecially true on the limbs and results fromthe pattern of development of the limb buds. For further information, consult a textbookof embryology.

Knowledge of the receptive field anddermatomal maps is fundamental inexamination of any complaint that involvesanesthesia, analgesia, hypesthesia orhypalgesia over a portion of the body. Forexample, a patient with an anesthesia on theposterior side of the leg, running from overthe buttocks down to the most lateral toemost likely has a compressed or damaged S1dorsal root, and a disk problem might besuspected. On the other hand, the patientwith an analgesia over the middle of theabdomen, in the general region of the rectusabdominis muscle, extending upward toabout the region of the clavicle cannot havedamaged a dorsal root or even a group ofdorsal roots; the damage must be to theanterior thoracic rami. In the first case, youwould look for damage somewhere betweenthe dorsal root ganglion and the spinal cordand, in the second case, somewhereperipheral to the ganglion.

Several diseases involving the dorsalroot ganglia are conspicuous because of theirdermatomal patterns of symptoms. Tabesdorsalis, a syphilitic infection of the dorsalroot ganglia, often exhibits a dermatomalpattern of hypesthesia because the spirocheteshows a preference for larger myelinatedfibers. Pain and thermal sensations arenormal in the affected area. Herpes zoster,a viral infection of the dorsal root ganglia,sometimes called shingles, is characterizedby the appearance of a vesicular rash in thedermatome of the affected root.

Knowledge of the dermatomes has otheruses besides diagnosing dorsal root damage.

In cases of spinal cord transection, the levelof section can often be determined byreference to the pattern of sensory loss. Thesame is true for tumors of the spinal cordthat result in a sensory loss. Later we willsee that the pattern of motor deficits isequally telling in the neurological exam. Many times visceral pain is felt to be on thesurface of the body (so-called referredpain). Often this pain is localized to adermatome, and knowledge of thedermatomal pattern can lead the alertclinician to the internal organ that isinvolved.One of the striking features of the

organization of the nervous system is that apicture of the body (though distorted) can bemapped onto the various tracts and nuclei ofascending systems all the way to the cerebralcortex. The tracts are formed so that spatialinformation from the periphery is preservedin the spatial arrangement of the fibersthemselves. This type of organization iscalled a somatotopic representation,referring to the organization by place,"topos," on the body, "soma." The dorsalcolumns, for example, are formed by theaddition of new fibers, at progressively morerostral segments, to the lateral aspect of the

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Figure 6-3. Receptive fields of the peripheral nerves are illustrated on the outside of both views of the figure.

Dermatomes of the dorsal roots are illustrated on the inside of both view s. Shown are the regions of hypesthesia

following nerve or root damage. (Curtis BA, Jacobson S, Marcus EM : An Introduction to the Neurosciences.

Philadelphia, WB Saunders, 1972)

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Figure 6-4. Spinal dermatomes plotted alternately on opposite sides of the body to illustrate the entire extent of

the dermatomes. This figure should be compared with Fig. 6-3. (Turek SL: Orthopaedics: Principles and Their

Application, 3rd ed. Philadelphia, JB Lippincott, 1977)

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Figure 6-5. The somatotopic organization of the dorsal

columns and the spinothalamic tract and the functions

classically attributed to each. (Brodal A: Neurological

Anatomy, 2nd ed . New York, Oxford Univ. Press, 1969)

columns. This results in an organizationsuch that the dermatomes are laminated,with the sacral segments representedmedially and lumbar segments more laterallyin the fasciculus gracilis and the thoracic andcervical segments successively morelaterally in the fasciculus cuneatus. Thisorganization is illustrated in Figure 6-5.

As a result of this somatotopicorganization, it is possible for a spinal cordtumor to disrupt transmission through onlythe medial fascicles of the dorsal column,producing sensory disturbances in the lowerlimbs, or through the lateral fascicles,producing sensory disturbances only in thearms. However, it would be extremelyunlikely that any lesion of the dorsalcolumns could produce a sensorydisturbance localized to just one dermatome.

The spinothalamic tract likewise appearsto be somatotopically organized, but becausethe fibers are crossed the organization isreversed such that fibers from caudalsegments lie laterally, being displaced thatway by the progressive addition of fibers tothe medial aspect of the tract. (Again, seeFigure 6-5). This is presumably whysuperficial cuts in spinothalamictractotomies produce immediate analgesiaand athermesthesia, i.e., the loss oftemperature sensations, only in thecontralateral lower limb, with graded, morerostral losses resulting from deeper cuts. These deficits are always contralateral to thedamage as opposed to the ipsilateral lossesthat occur with dorsal column lesions.

It should be mentioned at this point thatthe somatotopic maps are summarydiagrams and should not be taken to indicatethat within any marked zone are found onlyfibers of that type. This is a mistake madefrequently. For example, in Figure 6-5, aclosed figure surrounds the location of the

corticospinal tract; within that figure arefound many fibers that are not part of thecorticospinal tract. The same warningapplies to the somatotopic zones within thedorsal columns or spinothalamic tracts. Within the zone marked for thoracic fibersare found fibers from other levels as well,but the majority appears to be from thoracicsegments. This may be one reason whyunpredicted effects on sensation are found

following controlled tractotomies that do notencroach on the neighboring regions. In anycase, these somatotopic maps, whetherderived from physiological or anatomicalobservations, should be treated as statisticalstatements only.The somatotopic arrangement is preserved

at higher levels of the nervous system,though the orientation changes. In the dorsalcolumn nuclei, the arrangement found in thedorsal columns is preserved, with lowerlimbs represented medially and upper limbslaterally. As they course into the mediallemniscus, the fibers of the gracile nucleustake up a ventral position, and those fromthe cuneate nucleus a dorsal position. Fibers

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Figure 6-6. The somatotopic organization of

the postcentral gyrus of the cerebral cortex

and the position of somatosensory area II

Figure 6-7. A detailed somatotopic map of the

postcentral gyrus (Penfield W and Rasmussen T:

The Cerebral Cortex of Man. New York, Macmillan,

1969)

of the spinothalamic tract join the lemniscus,after it decussates, in such a way that theyform a cap on the lemniscus, with the legrepresented dorsally and the arm ventrally. Addition of fibers from the trigeminal to themost dorsal aspect results in a representation(from top to bottom) of: face, lower limb,upper limb, trunk and lower limb. In thethalamus, the lower limb fibers terminatelaterally and those of the upper limb moremedially (the opposite of the spinal cord),with the face represented most medially inVPM. The fibers again cross each otherupon leaving the thalamus with the resultthat the lower limb is represented on themedial aspect of the hemisphere, whereasthe representation of the upper limb is morelateral and that of the face most lateral. Theresulting organization is illustrated in Figure6-6. Another representation of the bodyexists on the cerebral cortex, the so-calledsomatosensory area II (SII). Its organizationis the inverse of that already described forsomatosensory area I, namely, face, arm, andleg in that order, going laterally. Area II,however, is not visible on the exposedsurface of the human cortex, but is buried inthe Sylvian fissure.

These are rough maps at best. Adjacentareas in skin are represented in adjacent

areas of the nervous system. However, it isgenerally not true (or not known to be true)that adjacent points on the skin haveadjacent representations.

This description of the organization of thesomatosensory cortex is supported byrecordings made directly from the cortex inhumans as well as animals. It is possible toopen the cranium of an awake human patientunder local anesthetics and record from orstimulate the cortex while the patient isawake. This is normally done duringsurgery to remove a tumor or to treat anepileptic condition. When recordings aremade under such conditions, it is usuallyfound that the largest amplitude responsesfor stimulation of the hand are found on thelateral aspect of the postcentral gyrus,whereas those for stimulation of the leg areon the medial aspects or buried in themidsagittal sulcus. Similarly, if the cortex is

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stimulated directly, it is possible to elicitsensations referred to a particular point onthe body, not to the cortex itself. Eventhough it is the cortex that was stimulated,the feeling is one of being stimulated on theappropriate body part. The particular pointof reference depends upon the site ofstimulation in the same orderly manner. Adetailed map of the human cortex has beenmade in this way by Dr. Wilder Penfield, thedistinguished neurosurgeon. His map isshown in Figure 6-7. Notice that the foot isrepresented on the medial aspect of thehemisphere in the midsagittal sulcus withthe leg represented on the medial part of theexposed hemisphere, and the trunk, arm andhand more laterally. The face is separateand more lateral still. The amount of tissuedevoted to the hand and face isdisproportionately large. Some investigatorsthink that this reflects the heightenedsensitivity of these parts compared to thetrunk and legs, as indicated, for example, bythe differences in two-point thresholds.

A caution should be introduced in regardto somatotopic maps like that shown inFigure 6-7. In humans, these maps areobtained in two ways. In the first, varioussites on the cortical surface are stimulated,where the patient feels a sensation to be isnoted, and a mark is made on a photographof the exposed cortical surface. Not everypoint on the surface is stimulated in such anexperiment; neither is a sensationexperienced at every point of thehomunculus in every experiment. Rather, itis assumed that if stimulation at two pointson the surface of the brain leads tosensations at two points on the body, thenstimulation between the points will lead to asensation localized to the body surfacebetween the two original points. In otherwords, it is assumed that an intermediatevalue principle holds for such maps–a fact

not known to be true.The second mapping method involves

recording from the cortex while stimulatingthe skin. Animals cannot indicate the natureor location of any sensations they have, sothis is the only method available in animalexperiments. It is assumed that the evokedpotential (the combined synaptic responsesof all active nerve cells near the recordingpoint) recorded from the cortical surface, isan indicator of the occurrence of a sensation(an assumption that is questionable andprobably incorrect). Points on thehomunculus are then indicated at placeswhere the evoked potential with largestamplitude occurs; the fact that potentials ofsmaller amplitude are evoked in wide areasof the cortical surface by the same stimulusis ignored. Activity initiated at a point onthe body surface converges upon an area ofcortex, not upon a point of cortex as thehomunculus is usually taken to imply.That this method of mapping is grossly

reliable is indicated by the rough similarityof maps made in different patients and bythe similarity of maps made by stimulatingthe skin and, in different patients, bystimulating the cortex. However, such mapsdo vary from individual to individual. Somestudies (Woolsey, Erickson, Gilson: JNeurosurg 51: 476-506, 1979) clearly showthat in some individuals the foot isrepresented within the midsagittal sulcus,whereas in others it is represented laterallyon the exposed surface. It is also importantto remember that figurine maps arecomposites from a number of patients, eachof whom was studied only to a limitedextent. Thus, the foot may be studied in onepatient, the arm in another, and so forth. Ifthere is variability in the position of therepresentation, then the amount of tissuedevoted to a particular area of skin is likely

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Primary somatosensory corticallesions produce hypesthesia anddisabilities in using somatic sensoryinformation to solve problems.

to be overestimated in composite maps.It should always be kept in mind that

these patients are undergoing surgery for anabnormality, tumor or epileptic focus, in ornear the area being studied, and theircortices are not entirely normal. Thesignificance of such maps in understandingcortical organization is also brought intoquestion by the fact that if maps are madeusing minimum latency of the evokedpotential (the time between the stimulus andthe beginning of the potential) rather thanamplitude as a measure of activity, then acompletely different homunculus map isobtained. Who can say whether latency oramplitude is more important?

Cerebral mechanisms of sensationThe precise reason for this somatotopic

representation in all of the main sensorypathways and nuclei is unknown, thoughmany are of the opinion that it provides thefunctional and anatomical substrate forcoding of spatial localization. Perhaps itdoes, but perhaps it exists as a mechanicaland architectural convenience for a nervoussystem developing through phylogeny from

a simple segmented, metameric pattern.To see something of the controversy

regarding this topic, take a look at JH Kaas.Topographic maps are fundamental tosensory processing. Brain Res. Bull. 44:107-112, 1997 and RJ Weinberg. Aretopographic maps fundamental to sensoryprocessing? Brain Res. Bull. 44: 113-116,1997.

Many people have the mistaken idea that

the cerebral cortex is where the real businessof the nervous system is transacted and therest of the nervous system is just aconduction pathway to it. This is not thecase. For instance, removal of the hand areaof the postcentral gyrus does not produceanesthesia in the hand. What it doesproduce is an elevation of the threshold forsensation at the hand, an hypesthesia, and asevere deficit in discriminating the spatialaspects of stimulation, i.e., in using sensoryinformation to solve problems. The patient,following such a lesion, has difficulty inpointing to a site on the skin that has beenstimulated (atopognosis); has difficultyrecognizing words written on the skin(agraphesthesia); and has difficulty inidentifying objects by feeling them(astereognosis). The clinical literaturecontains some studies that indicate thatsensory defects following damage to theprimary somesthetic cortex are more severethan claimed above and some that indicatethey are less severe. The great variabilitymay be ascribed to a number of factors: (1) Naturally occurring lesions are seldomconfined to the primary somesthetic cortex;one would expect the nature of the sensorylosses to depend upon the total extent anddistribution of damage. (2) The measures of sensory capacity usedin different studies vary widely; results maydepend upon the test employed. (3) In cases of clinical ablations, the lesionswere made in tissue already damagedsufficiently to produce epileptic dischargesor already invaded by tumors; the influenceof these factors cannot be evaluated. Thisis especially important when there has beenno measure of the sensory capacity of theindividual before the surgery. (4) What is usually reported is the locationand amount of tissue the surgeon removed,

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but no information is available aboutwhat influence the surgery may have hadon surrounding tissues. This influenceshows up in cases where, after unilateralablation, deficits are seen bilaterallywhen the patient is compared to normalpeople (Corkin S, Milner B, RasmussenT: Arch Neurol 23:41-58, 1970). Without postmortem examination, therecan be no idea how extensive this effectmay have been.(5) Even when there is postmorteminformation, it is difficult to determinehow much of the damage present wasdone before, at the time of, or after thesurgery.The minimum effect of a cortical lesion

probably is not a good indicator of thefunction of the tissue because the minimallesion probably doesn't damage the tissueenough. The maximal effect probablyrepresents the function of too many tissues. Therefore, it seems likely that some middlepoint is at least a good approximation of thedeficits due to removal of this tissue. Itreally should not surprise us that the cerebralcortex is not required for sensation. Consider how well a frog can sense and actupon stimuli applied to its skin, and it has nocerebral cortex at all.

How can we account for the fact thatsensations can be evoked by stimulation ofthe human somatosensory cortex? Earlystimulation experiments resulted insensations described by the patients astingling or prickling sensations or a feelingof numbness, and so it was thought not to bepossible to evoke "real" sensations, such astouch, by direct stimulation. With improvedtechniques, such sensations have beenevoked, but it is necessary to pass currentthrough the electrodes for about 0.5 sec, atime much longer than that needed simply to

excite local neurons. Under thesecircumstances, identifiable, well-localizedsensations have been evoked. Certainly asensation does not require a cortical neuronto discharge for 500 msec, because for astimulus to the skin, the stimulus is sensedand a response is executed by a normalperson in about 200 msec. One explanationis that the sensation occurs as the result ofsome event occurring at a distance from thecortical stimulation site and thattransmission from the cortex to this elementrequires the generation of more than onespike in the cortical neurons. Anotherpossible explanation for this discrepancymay lie in the distinction between sensationand perception. It may be that a stimuluscan be sensed and acted upon at one level ofthe nervous system, but only perceived(come into consciousness) if it elicitsactivity elsewhere. Old ideas about"subliminal perception" would make sensein this context. (Experiments in “blind sight”form the visual equivalent to this. Theseexperiments are described in Chapter 7.) Itis also possible that the somesthetic cortex isnot part of the "normal" pathway by whichthe conscious sensation (perception) iselicited by a stimulus to the skin. Theobservation that cortical ablations do noteliminate but merely elevate thresholds ofsensation begin to make more sense in thelight of these considerations.

Central mechanisms of pain sensations Stimulation of the surface of the cortex

seldom leads to painful sensations. Neitherdoes removal of any portion of the cerebralcortex eliminate pain sensations; but, this isnot to say the cortex plays no role in painperception. We have already had occasionto point out that removal of the prefrontallobe, a prefrontal lobotomy or lobectomy,

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results in a dissociation between thediscriminative and affective aspects of pain. When stuck with a pin, such a patient re-ports that it hurts, but it doesn't bother him. There is also the well-known suppression ofpain sensations that occurs as an everydayevent, but is more prominent during militarybattles. A person may be wounded seriouslyand not be aware of it, or he may suppressbeing aware of it during concentration onsome other activity. Whether this sort ofsuppression is of cerebral cortical origin isunknown, but it could be.

Pain sensations can be elicited bystimulation in some areas of the thalamus. For example, stimulation in the ventral andposterior parts of VPL and VPM in awakepatients evokes excruciatingly painfulsensations localized to the appropriate areaof the body (appropriate according to thethalamic somatotopic organization). Lesionsin this area have sometimes proven effectivein eliminating, for a short time, certain formsof spontaneous pain such as causalgias,burning pain caused by damage of aperipheral nerve, and phantom-limb pain,pain experienced in a limb that has beenremoved (occurs in 5-10% of amputees,especially those with pain in the limb beforeamputation). Other areas of the thalamuscontain cells that respond to noxiousstimulation or when stimulated, lead to painsensations, or, when removed, temporarilyreduce or eliminate pain sensation, but as yetwe do not have a thorough understanding ofthis system. In cases of thalamic lesions,pain is alleviated for a short time, but soonreturns, often with even greater severity thanbefore the lesion; this condition is termedhyperpathia. To the patient this may meanan endless series of surgical lesions, he maywish had never begun, just to keep ahead ofthe advancing pain intensity. It has been

customary to think of the experience of painas occurring in the thalamus simply becauseit is the "highest" center in which it can berecorded, evoked, or blocked.Gate theory. In most sensory systems there

exists a phenomenon known as maskingwhich is an increase in the threshold forperception of a given stimulus caused by thepresence of another stimulus. In audition,tones of similar frequencies tend to maskeach other. There is only a slight increase inthe threshold for detection of a 400 Hz tonein the presence of an 800 Hz tone, but thereis considerable increase in threshold for a750 Hz tone in the presence of an 800 Hztone. In the olfactory system, strong odorstend to mask weaker odors. Similarmasking phenomena occur in thesomatosensory system. Touching the skinnear a hair will block the sensation evokedby flicking the hair with a pencil point. Also, weak cutaneous stimulation andsometimes even strong stimulation canblock or reduce cutaneous pain sensations. (All of these masking phenomena probablydo not have the same neural mechanisms,but they are similar phenomenologically.)A number of properties of pain perception

(including masking) have led to the proposalof the Gate Theory of Pain. (1) Counter-irritation, such as lightly rubbing the skinnear the painful area, can relieve the painexperienced; (2) under certain circumstances(for example, in causalgias), gentlestimulation of an injured area can produceintense pain, though it does not produce painon normal skin; (3) intense, spontaneouspain often results from pathologicalconditions, such as tabes dorsalis, in whichlarge myelinated fibers (which don't carrypain signals) are affected preferentially; (4)pain often results in the ten second periodafter ischemic pressure-block of a nerve

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Figure 6-8. The circuit diagram of the

gate-control theory of pain perception as

proposed by Melzack and Wall (1965)

while large fibers fail to conduct; and (5)stimulation of the dorsal columns ipsilateralto the pain often produces relief of pain.

To account for these observations,Melzack and Wall proposed that theperception of pain depends not only uponpain signals in small fibers, but also uponthe balance of activity in large myelinatedmechanoreceptive fibers (A" and Aßfibers) and small myelinated andunmyelinated nociceptive fibers (A* and Cfibers). It is important to remember that notall small fibers are nociceptive–some aremechano- or thermoreceptive. Melzack andWall proposed that, under normalconditions, anything that increases theactivity of the large mechanoreceptive fiberstends to reduce pain, and anything thatincreases the activity of small nociceptivefibers tends to increase pain by changing thebalance. Specifically, they proposed themodel illustrated in Figure 6-8. Accordingto the theory, the transmission cells [Tcells; originally thought to be cells of thespinothalamic tract] activate neuralmechanisms that produce pain perception,i.e., T cell activity is interpreted by thecentral nervous system as pain. A gate cell,or G cell (originally thought to be cells ofthe substantia gelatinosa), is capable of

modulating the activity in afferent pathways(of both large and small fibers) to the T cell,before it gets to the T cell. The G cellactivity is, in turn, modulated by activity inboth large and small primary afferent fibers. Specifically, volleys in both large and smallfibers excite the T cell (drive its membranevoltage toward the critical firing level),whereas the same volleys in large fibersexcite the G cell to discharge and the samevolleys in small fibers inhibit the G celldischarge (drive its membrane voltage awayfrom the critical firing level). Activity in theG cell inhibits (reduces or blocks)transmission from both large and smallfibers to T cells. Cortical and subcorticalinfluences on the gate control mechanism,called “Central Control” in the figure, areindicated in the diagram of Figure 6-8. Thisdiagram is just one module of many; thereare many T and G cells and, of course, amillion or so afferent fibers.How does this theory account for the

observations above? (1) Lightly rubbingthe skin increases the discharges of largemyelinated fibers and, in turn, the dischargeof the G cell. This results in a decreasedtransmission through both large and smallafferent fibers to the T cell which, of course,is perceived as a reduction in pain sensationbecause the severity of pain sensation isproportional to the frequency of firing of theT cell. (2) In causalgias, there can be aselective destruction of the large fibers in theaffected nerve. This will result indiminished G cell activity caused by reducedexcitation from large fibers and theunopposed inhibition from small fibers,thereby opening the gate and letting the Tcell receive excitation through the large andsmall fiber pathways. The result will bepain evoked by even the lightest touch. (3)Many C fibers are slightly spontaneouslyactive and, when the gate is open due to

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According to the Gate Theory,perception of pain depends not onlyupon pain signals in small fibers, but alsoupon the balance of activity in largemyelinated mechanoreceptive fibers andsmall myelinated and unmyelinatednociceptive fibers.

large afferent fiber damage, these C fibersare free to excite the T cell. When theexcitation builds up enough to bring themembrane potential of the T cell to thecritical firing level, spontaneous pain will beexperienced. (4) After an ischemic block ofa peripheral nerve, the large fibers recovermore slowly than the small fibers. Therefore, there is a period of time when thegate is open due to the absence of the largefiber activity. (5) The dorsal column fibersare branches of the large myelinated fibersof the medial division of the dorsal root. Stimulation of the dorsal columns sendsimpulses up (orthodromic) and down(antidromic) the fibers of the columns. When the antidromic impulses reach thepoint of bifurcation near the dorsal rootentry zone, action potentials are set up inboth the dorsal root (antidromic) and in thebranch that descends into the spinal graymatter (orthodromic). The orthodromicimpulses act just like those from theperiphery in closing the gate by activatingthe G cell; thus, the pain is reduced. Smallstimulating devices have been implanted inthe dorsal columns or sewn to the dura overthe dorsal columns of patients with chronicpain. The patient can activate the devicehimself when the pain recurs. Some successhas been reported using this technique.

There was a flurry of excitement whenthis theory was introduced and with it a greatdeal of research. The original specificationsof the theory assigned to specific cells in thespinal cord the roles of G and T cells. Thesespecific cells do not seem to have all of theproperties of G and T cells. In addition,there are some examples of clinicalsyndromes that do not seem, at first glance,to fit the gate theory. In Friedrich's ataxia–ahereditary disease, symptoms of which areataxia, speech impairment, lateral curvature

of the spine, swaying, irregular movements,and muscle paralysis–there is a preferentialloss of large fibers without pain. Similarly,the polyneuropathy associated with renalfailure in adults is not associated withcomplaints of pain, although there isdestruction predominantly of large fibers. Nor do some other neuropathies make anysense in any current theory of peripheralnerve involvement in pain sensation. Fabry's disease–a rare phospholipid storagedisease–is associated with both pain and theloss of small myelinated fibers, and onehereditary sensory neuropathy is associatedwith loss of myelinated fibers, preserved Cfibers, and analgesia. One should bear inmind that none of these is a disease ofperipheral nerves alone. Friedrich's ataxiaalso involves sclerosis of dorsal and lateralcolumns of the spinal cord, including thepyramidal tract, and Fabry's disease involvespathological conditions of the cardiovascularand renal systems as well as skin and musclelesions. The effects on pain of these formsof polyneuropathy are not explained byreference to which peripheral nerve fibersare present or absent. Therefore, it may bethe involvement of central pain mechanismsthat makes these diseases appear to fit noexisting theory.

It should be kept in mind that not all pain isof peripheral origin, i.e., some pain does notarise from activity in nociceptors. Causalgias are a class of disorders involving

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Figure 6-9. The location of stimulus sites

within the periaqueductal gray matter

(shaded area) at the level of the superior

colliculus from which analgesia can be

produced in the cat

burning pain due to peripheral nervedamage, not receptor damage. Theimportance of the separation of "central" and"peripheral" pain is indicated by theobservation that patients often obtain relieffrom spontaneous pain of causalgias whenthe dorsal columns are stimulated, but thesame stimulation does not elevate thethreshold for pain induced by pinching theskin in the referral area of the causalgias. The stimulus also does not elevate touch andvibration thresholds. It appears thatcausalgias may have mechanisms differentfrom those of peripheral pain, but how theydiffer is as yet unknown.

A further indication of this differencebetween "normal" and "pathological" pain isthe result of attempts to close the gate byperipheral stimulation. In patients withcausalgias, stimulation of large-diameterfibers has been used to attempt to activatethe G cells and close the gate. In 1/3 ormore of such patients, partial to completerelief has been obtained, but the samestimulation has no effect on pain due tonoxious stimulation of the hand. Pain due tosqueezing the Achilles' tendon can berelieved by large fiber stimulation,suggesting that all sorts of "normal" painmay not be the same either. Similarly,morphine can decrease postsurgical tonicpain, but has less effect on acute pain ofmovement or removal of stitches. Nitrousoxide, on the other hand, depresses both andis perhaps the only true analgesic agent.

Endogenous pain suppression system. It is doubtful that the gate control theory,

as it was originally proposed, is adequate toexplain all types of pain, but it seemsreasonable that some similar gatingmechanism(s) are active in pain perception,either in the spinal cord or at some otherlevel of the central nervous system. In fact,

there is some evidence for such amechanism at the brain stem level. Stimulation of the periaqueductal graymatter of the brain stem (Fig. 6-9) producesanalgesia in rats sufficient to do abdominalsurgery and equivalent to a dose of 50 mg/kgof morphine, but without the muscularrigidity that accompanies such high doses. Itblocks withdrawal reflexes due to skinpinch, noxious heat, tooth pulp stimulation(supposedly evoking pure pain sensations),and chemical irritants. The analgesiainduced by a few minutes of high frequencystimulation lasts minutes, hours or days butis not a total analgesia because some parts ofthe body are unaffected. Again, pathologicalpain is blocked more easily than normalpain.

Injection of minute amounts of opiatedrugs into the region of the periaqueductalgray matter induces strong general analgesiasimilar to that obtained with systemic

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Figure 6-10. The endogenous pain suppression theory

includes a negative feedback system in which

spinothalamic tract cells (1), activated by noxious

input, activate cells of the periaqueductal gray

matter (2), which in turn activate descending

pathways from the nucleus raphe magnus (3) and the

locus ceruleus or nuclei subceruleus and

parafascicularis (4). At the segmental spinal cord,

interneurons (5 and 6) activated by these descending

impulses inhibit further activation of sp inothalamic

tract cells. Also shown are the sites of action of dorsal

column influences and morphine (Basbaum AI and

Fields HL: Ann Neurol 4:451-462, 1978).

morphine. The opiate-antagonist drug,naloxone, blocks the analgesic effects ofsystemic and microinjected morphine andreduces the effects of periaqueductal graymatter stimulation. The effects of morphineand stimulation are also reduced or blockedby depletion, with parachlorophenylalanine,of serotonin (5 hydroxytryptamine, 5HT), aputative excitatory transmitter substance,and blocked by lesions of the ipsilateraldorsolateral funiculus of the spinal cord. These latter observations prompted a searchfor a pathway descending to the spinal cordin the dorsolateral funiculus from the regionof the periaqueductal gray matter andcontaining serotonin. Such a pathwayoriginates in the nucleus raphe magnus ofthe medullary reticular formation. Stimulation within this nucleus alsoproduces analgesia similar to that seen withperiaqueductal gray matter stimulation. Subsequently, a synaptic link between theperiaqueductal gray matter and the nucleusraphe magnus has been demonstrated, andcells in both nuclei have been shown to beresponsive to noxious inputs as well as lighttactile stimulation.

At about the same time that stimulation-produced analgesia was being discovered,pharmacological investigations wererevealing the presence of receptors in thebrain to which opiates bind specifically. This suggested that there were naturallyoccurring morphine-like compounds in thebrain that could bind to these receptors. Subsequently, two pentapeptides, theenkephalins, and certain other peptides, theendorphins, were isolated from brain tissueand shown to have analgesic effects likemorphine when injected systemically or intothe ventricle. These compounds are found atmany places within the central nervoussystem, but, notably, they occur in theperiaqueductal gray matter and the area of

the spinal cord from which thespinothalamic tract has been shown tooriginate. The opiate receptors have alsobeen seen on the terminals of primaryafferent neurons in the dorsal horn; someinvestigators believe these are the terminalsof nociceptive axons.From the preceding observations, Basbaum

and Fields (1978) proposed what they calledan endogenous pain suppression system. The model, shown in Figure 6-10, proposesthat noxious stimulation excites nociceptors,which, in turn, excite cells of thespinothalamic tract, giving rise to pain

sensations. Spinothalamic fibers excite cellsof the periaqueductal gray matter, which, inturn, excite cells of the nucleus raphemagnus. The latter cells can also be excited

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The endogenous pain suppressionsystem proposes that activity thatleads to painful sensations also leadsto the prevention or reduction offurther pain sensations.

by nociceptive inputs via other pathways. Axons of raphe magnus neurons descend inthe dorsolateral funiculus, and their activityexcites interneurons in the spinal cord thatcontain endorphins as a transmittersubstance. When released, the endorphinsblock the release of transmitter substance(possibly substance P, another peptidecompound) onto spinothalamic tract cells,preventing or reducing further nociceptivedischarges in them. This is an example of anegative feedback loop in which the outputof a group of cells, in this case thespinothalamic tract cells, is used to reduceits input, in this case the amount ofnociceptive input. The effect of the systemis to reduce subsequent pain sensation. Themodel suggests that morphine acts byexciting the system at the periaqueductalgray matter.

This model explains the effects ofmorphine (systemically and locally injected),of periaqueductal gray matter and nucleusraphe magnus stimulation, and ofendorphins on pain sensitivity, at least inpart. However, naloxone administration andserotonin depletion only partially block theeffect of periaqueductal gray matterstimulation, implying that there must be anadditional mechanism for this effect.

This model requires that periaqueductalgray matter stimulation and morphineadministration actually result in inhibition ofnociceptive activity in spinal cord neurons. Studies have indicated that, in the rat,

injection of morphine into theperiaqueductal gray matter leads todecreased responsiveness to noxiousstimulation in some lumbar spinal cordneurons; others increase their activity or arenot influenced. In some of the inhibitedcells, naloxone returned the cell discharge tonormal despite continued noxiousstimulation. Periaqueductal gray matterstimulation does not influence the dischargeof most cells that respond to mechanical,non-noxious stimulation. The situations inthe monkey and cat are similar, but not quiteas neat. Stimulation of the raphe magnusnucleus inhibits both nociceptive and non-nociceptive, tactile activity in spinothalamicneurons. Thus, it is clear that not allnociceptive activity is inhibited bystimulation in regions that produceanalgesia; however, not all nociceptiveactivity is necessarily associated with painperception. As we shall see when wediscuss synaptic transmission (Chapter 13),it is not necessary to reduce nociceptiveinputs to a cell to zero in order to bring themembrane potential below critical firinglevel, preventing its discharge. Still, the linkbetween the cellular events in the spinal cordand the analgesia observed has yet to beestablished, so the model is tentative, but ithas already led to new pain treatments.

Referred pain. It is customary to classify visceral

sensations as either organic sensations or aspain sensations. Organic sensations arethose that signal a bodily need and thatusually lead to an activity designed to satisfythat need. Hunger sensations are anexample. All fibers that carry visceralsensation travel the viscera in the companyof autonomic efferent fibers and enter thespinal cord through the deep nerve trunksand the ventral ramus of the dorsal root.

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Referred pain probably occursbecause visceral pain fibers convergeonto the same pain pathways as donon-visceral or cutaneous fibers.

Figure 6-11. Schematic diagram

showing convergence of input from

pain fibers originating in skin and

visceral organs onto cells that signal

pain to the central nervous system.

Visceral pain is peculiar in that it is oftenfelt to be coming from the surface of thebody, not from the organ that contains thepain receptors. We say that the pain isreferred to the site on the skin. The area ofthe referral is always in the dermatomeinnervated by the same dorsal root(s) asthose supplying the irritated structure in theviscera. This is a case where knowledge ofthe dermatomes becomes an importantdiagnostic tool. Angina pectoris is a classicexample in which pain caused by anoxia ofthe myocardium is referred to the chest andarm. The pain fibers from the myocardiumoriginate in the dorsal root ganglia T1-T5,which have dermatomes on the chest frombelow the nipple up to about the level of theclavicle and also down the posterior aspectof the arm. It serves a clinician well tomemorize this distribution, because chancesare he will see it again.

There are a number of other examples ofreferred pain. Regurgitation of acid into theesophagus is sensed as burning painlocalized to the region of the lower end ofthe sternum ("heart burn"), whereas referredpain for inflammation of the appendix isexperienced in the lower right abdominalquadrant. It should be noted that not allvisceral pain is referred. Appendicitis isalso accompanied by diffuse pain near themidline at the epigastric level, and amyocardial infarction is usuallyaccompanied by deeper aching in the chestin the vicinity of the heart.

Referral of pain is not limited to visceralorgans. Pain in some nonvisceral organssuch as the peritoneum and the diaphragm is

also referred to the appropriate dermatomes. The pain fibers from the central region of thediaphragm travel in the phrenic nerve toenter the spinal cord at C3 and C4. Thus,pain in the diaphragm, for example, caused

by subphrenic abscess, is referred to theregion of the neck and shoulders. Referralof pain from the diaphragm also occursfollowing a gynecological test to determinethe patency of the fallopian tubes, Rubin'stest. In this test, CO2 is forced into theuterus and out through the tubes, and if theyare patent, the bubble of gas escapes past thefimbria into the peritoneal cavity. It causesno sensation in the horizontal position, butupon rising the patients often report pain inthe shoulder caused by the localization ofthe bubble beneath the diaphragm. The painsubsides, of course, as the gas is absorbed.The mechanism of the referral is probably

the same for visceral and other somatic pain. The visceral pain afferent fibers likelyterminate on the same central cells andinfluence them in the same way as thecutaneous and muscle pain fibers of thatdermatome (Fig. 6-11). Throughexperience, the discharge of those centralcells has become associated with pain of thebody surface, visceral pain being aninfrequent event. The brain thus interprets

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activity in those cells as pain at the body surface, not deep pain. Whatever the natureand the location of the central painmechanism, it “knows” only that the centralcell has discharged; it does not know whatmade it discharge.

Pain treatment. The most common treatment for pain is

the administration of so-called analgesicdrugs. This is, perhaps, an unfortunate term,because few of these drugs produceanalgesia in the sense of insensitivity topain. In most cases, they produce painrelief–aspirin relieves headaches–but painsensitivity is not lowered. The patient stillresponds with the same sensitivity tonoxious heat, damaging mechanical orchemical stimulation or electricalstimulation. As already mentioned, evenmorphine does not produce analgesia. General anesthetics may produce analgesia,or they may not. We only know that thepatient does not report experiencing painunder the influence of a general anestheticagent, but withdrawal reflexes and reflexchanges in blood pressure still occur inresponse to painful stimulation. Perhaps thepatient felt pain, but just didn't remember. No one can say with certainty. We will seethat most surgical treatments for pain alsoproduce pain relief, not analgesia, but, ofcourse, that is what the patient really wants.

Chronic pain has been treated with anumber of destructive surgical interventions. Dorsal rhizotomies have been performed forchronic pain owing to malignancies,vertebral disk disease, spinal trauma andother causes, but the success rate (completepain relief) is less than 30%. There are, ofcourse, fibers other than nociceptive fibersin the dorsal roots, and losses occur in otherthan pain sensations. The use of thisprocedure is further complicated by the fact

that, even though a nerve block by localanesthetics may alleviate pain totally,subsequent rhizotomy of the same roots maybe without effect. A similar treatment fortrigeminal neuralgia or tic douloureux (asevere, episodic pain in the face associatedwith large-fiber damage and triggered bygentle but not intense stimulation of theface), involving thermocoagulation of thetrigeminal roots or ganglia within theforamen ovale, has achieved a success rateof 90% to 100%, though up to 17% requiredmore than one treatment. This treatment hasthe advantage of preserving touch sensationin the analgesic field in many cases, but painstill recurs in 22% of cases. The cause ofthe relief may not be destruction ofnociceptive fibers in every case, because amistaken coagulation of the wrongtrigeminal (the one contralateral to the pain)led to pain relief for two years in one patient.The notion that the spinothalamic tract was

the pain pathway provoked a great manyanterolateral cordotomies (or spinothalamictractotomies) for the relief of chronic pain. Initially, these were done surgically, but laterthey were done percutaneously by insertingmetal electrodes into the spinal cord(without a laminectomy) and coagulating aportion of the anterolateral quadrant. Asmentioned before, this procedure neverproduces permanent pain relief. Adysesthesia, a persistent, painful sensationproduced by gentle stimulation, usuallydevelops sometime after a cordotomy, and itworsens with time. For these reasons,cordotomies are seldom done except interminal-disease cases.It is possible to make small lesions in

specific structures within the brain bypassing a small amount of current throughan electrode placed in that structure. Thecurrent produces heat that destroys the

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nearby cells. Such electrodes can be placedaccurately using stereotaxic coordinates, aCartesian coordinate system, read from anatlas and referenced to particular points onthe head. The position of the electrode canbe checked using known properties of thecells in the region, e.g., the cells of thenucleus ventralis posterolateralis of thethalamus are known to discharge in responseto skin stimulation, and by X-ray imaging. Lesions have been made in the variousrelays for nociceptive information in thethalamus or mesencephalon. But, everyonewho has used this type of intervention hasfound the same result: there is initial relieffollowed by rapid return of pain. Even largeand bilateral lesions fail to relieve pain, andusually lead to exacerbation of preoperativepain or a dysesthesia, that is worse than theinitial complaint. At present, there is littlejustification for thalamotomy in paintreatment.

The causalgias are burning painsassociated with peripheral nerve damage,often associated with penetrating wounds,and they are frequently exacerbated ortriggered by emotional and thermalstimulation. These pains can also betriggered by light touch or any stimulus thatelicits a startle reflex. The involvement ofemotion suggests that the sympatheticnervous system may play a role in causalgia;in cases where pain is exacerbated by suchstimuli, sympathectomy has produced atleast some pain relief. Paravertebralsympathetic nerve blocks are goodindicators of the success of sympathectomy. This form of treatment has also been usedfor pain relief in disease confined to thevisceral capsule, e.g., angina pectoris, aorticaneurysms, and postcholecystectomyneuralgia, but seldom is effective for paindue to malignancy. For causalgia with

emotional exacerbation, good, long-termpain relief has been obtained in up to 83% ofcases where sympathectomies have beenperformed. The mechanism of the painrelief is not known, but (1) abolition ofvasomotor and sudomotor efferentdischarge, with relief from ischemia, and (2)interruption of accessory sensory pathwayscarrying pain discharges from blood vesselshave been suggested as explanations. Pain due to hormone-dependent tumors is

usually not responsive to surgical or nerve-block treatments, because the tumors arecommonly metastatic and distributed overwide areas or in different organs. Somepatients suffering from this sort of chronicpain have been treated by chemicalhypophysectomy. A small amount ofethanol injected in the region of the pituitaryproduced complete, immediate and long-lasting relief in 88% of the patients in onestudy, and some of the remaining patientsalso received relief when the procedure wasrepeated. The treatment not only results inpain relief, but there is usually an arrest orregression of the metastasis. Twohypotheses suggest that (1) hormonespotentiate transmission through sensorypathways, and removal of hormones reducespain discharge transmission, and (2) ethanolworks not only on the pituitary, but alsodiffuses to surrounding tissues that are in thepain pathway. Hormones are known topotentiate sensory transmission, butpotentiation of nociceptive sensorytransmission has not been studied.Percutaneous stimulation and dorsal

column stimulation to activate large-diameter fibers have already been mentionedfor pain treatment. Stimulation of aperipheral nerve, central to nerve damage ina patient with causalgia, produces immediatepain relief that outlasts the duration ofstimulation. Two minutes of stimulation at

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Figure 6-12. Stimulation sites in human patients from

which pain relief has been obtained. Electrode tracks are

shown, along which the stimulation sites are marked with

different symbols for each patient. These tracks traverse

the periventricular gray area along the medial aspect of

the nucleus parafascicularis of the thalamus (Richardson

DE, Akil H: J Neurosurg 47:178-183, 1977).

100 Hz has produced relief lasting up toseven hours; eventually pain returned,sometimes with an overshoot (it was worsethan before stimulation), but repeatedstimulation produced repeated relief. Suchstimulation has been effective in 70-85% ofthe patients in different clinics. Percutaneous stimulation has been used totreat headache and pain due to burns andabrasions; relief is more frequent for thistype of new pain than for chronic pain. In agroup of patients with chronic low backpain, 39% obtained complete relief, 28%obtained some relief, but 33% obtained norelief. There are three hypotheses advancedto explain pain relief by percutaneousstimulation. Closure of the pain gate in thegate control theory is one explanation. Blockage of transmission in small fibers as aresult of repeated, high-frequencystimulation is another. Masking of painsensation by evoked paresthesias is yetanother explanation. This last alternativedoes not seem to explain all cases, becausepain usually fades out gradually duringstimulation and gradually reappears, whereasthe paresthesias appear abruptly withstimulation and disappear before pain recurs.

Dorsal column stimulation has been usedmost often in treatment of spinal columndisk pain. Some patients experienceparesthesias and pain relief duringstimulation, but both disappear whenstimulation ends. In others, paresthesiasmay last up to 30 minutes longer thanstimulation, and pain relief up to four hourslonger. Pin-prick pain, light touch, andvibration sensation, and stereognosis areunaffected by dorsal column stimulation, asthey are by dorsal column lesions (Friedman,Nashold, Somjen, 1974). Dorsal columnstimulation cannot relieve postoperative paincaused by implantation of the stimulator or

pain due to long-bone fracture, but it hasbeen effective in 81% of the cases of diskpain.

The experimental observations of theeffects of stimulation of the periaqueductalgray matter in rats have now been extendedto cats and monkeys and, finally, to man. Inpain patients, various forms of chronic pain,including disk pain, tumor pain andphantom-limb pain, have been relieved bysuch stimulation, without any apparentinfluence on other sensory modalities(vision, etc.) or submodalities (light touch)or changes in motor or intellectual activity. In some cases, acute experimental pain hasalso been blocked, but usually with moredifficulty and for shorter times. Thediencephalic periventricular gray matter, thepretectal nucleus, and some hypothalamicsites have also produced analgesia whenstimulated (Fig. 6-12). Medialperiventricular thalamic structures arepreferred targets for stimulation in humans,because periaqueductal stimulation usuallyproduces unpleasant sensations, includingnystagmus and nausea. Chronic pains

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beginning after implantation of stimulatingelectrodes may not be influenced bystimulation; electrically induced, radiantheat-induced, and ischemic exercise-inducedpains may also be unaffected. Whenpatients are allowed to control stimulation, atolerance, which generalizes to opiate drugs,may develop in 4-5 weeks, but if use islimited, this tolerance does not develop. Bilateral pain relief occurs with unilateralstimulation. About 75% of the patientstreated with this kind of stimulation (in onestudy) received at least some relief frompain; many received complete relief. In 5 of6 patients, naloxone administration reversedthe relief that resulted from stimulation(Richardson and Akil, 1977). In anotherstudy, similar stimulation had no effect onpain sensation in any patients (Mazars,Merienne, and Cioloca, 1979). This form oftreatment is not much used because of theadvent of intraspinal and intraventricularadministration of opioids. It is, however,still used in treatment of deafferentation painwhere it successfully yields long-term reliefin about 30% of patients (Gybels, Kupersand Nuttin, 1993).

The treatment of choice for pain is notalways clear; nor is it clear that a singletreatment is good for all types of pain. Earlyattempts at treating pain with a newprocedure are often more effective than laterattempts. One should guard against beingoverly optimistic about the effectiveness ofnew treatments. In a review, Shealy (1974)concluded that "traditional destructive pro-cedures–cordotomy, cingulumotomy,rhizotomy–are not only almost useless(except in cancer) but they cause far moreharm than good, and they interfere withsuccess of other procedures." In cancer, thepatient usually does not survive long enoughto suffer the harm of these procedures. Themechanism of action is not known for any

pain treatment. Most do not produce trueanalgesia but only pain relief. Manyproduce only transient relief and, for none,has an appropriate control procedure beendone to allow evaluation of the effectivenessof the treatment itself. For example,trigeminal coagulation produces pain reliefin most cases of trigeminal neuralgia, butsimple manipulations without destructioncan also produce relief. Pain is, indeed, acurious phenomenon!Acupuncture. The practice of

acupuncture in treatment of disorders isvery old in China, but interest in it has beenstirred in this country by demonstration thatit can be used for analgesia. The techniqueessentially is to insert metal needles throughthe skin at certain critical points and then toeither manipulate them or stimulate throughthem using mild electrical currents. Exactsites and number of sites are determined bythe position in which the analgesia isdesired. The patient usually reports atingling, pricking or numbing sensation dur-ing stimulation of the needles with astimulus strength that is great enough toexcite A" fibers and perhaps the largest A*fibers. Under this intervention, everythingfrom minor dental work to major abdominaland thoracic surgery is performed withoutanesthetic agents or their side-effects. Twoadvantages of the procedure are a more rapidrecovery and the absence of any need forclose supervision during recovery.One is at first tempted to interpret the

acupuncture phenomenon in terms of thegate theory. This temptation is brought onby the rather selective excitation of largemyelinated fibers by the needles and theirstimulation. However, in the gate theory,the large and small myelinated fibersoperating the gate supposedly enter the samespinal cord segment. Conversely, the

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acupuncture needles are often placed in thehand or ear lobe for procedures in the lowerabdomen, a separation of many segments forentry of the appropriate afferent fibers. Indeed, some variation of the gate theorycould be invoked to explain thephenomenon, but pathways which might beinvolved are not known at this time.

In China, acupuncture is used in about30% of the hospital surgical procedures. Ifthe procedure is so useful, why isn't it usedin 100%? The most likely answer is that itonly works in 30% of the cases. This isabout the same proportion of cases thatreceive relief from placebo treatments orhave surgical procedures under hypnosis. Itis reasonable to suggest that the monotonousstimulation has a somewhat hypnotic effectupon the patient. On the other hand,acupuncture has been reported to beeffective on animals and small children,suggesting that hypnosis is not the onlyexplanation, if it is an explanation at all.

We should recall that some superficialpains can be blocked by intense stimulationor counter-irritation. This intensestimulation can be in the form of dryneedling, intense cold or injection of normalsaline. Treatment with mustard plasters andblistering agents may also be considered thesame form of treatment, sometimes calledhyperstimulation analgesia. It seemsparadoxical that intense stimulation shouldrelieve pain from intense stimulation, but, insome cases, it works. Some investigatorshave suggested that acupuncture may be justanother case of hyperstimulation analgesia. The acupuncture needles apparently have noeffect on pain unless they are moved or anelectrical current is applied, implying asignificant input to the CNS is required forthe analgesia. However, analgesia is usuallyproduced by hyperstimulation near the area

of injury; acupuncture needles are effectiveat a distance.

Summary.Afferent fibers enter the spinal cord

through the dorsal roots and enter the majorascending pathways by synapsing atsegmental levels or by ascending directly inthe dorsal columns or both. Some second-order neurons at the segmental level cross tothe contralateral ventral white matter andascend as the spinothalamic tract. Fibersfrom the face enter through the trigeminalnerve and synapse in the trigeminal nuclei. Second-order neurons in the dorsal columnsystem arise from the dorsal column nuclei. Third-order neurons in all three pathwaysarise from the thalamus and ascend to thecerebral cortex. Sensory submodalitiesusually associated with the dorsal columnsystem are touch, pressure, vibration, andposition sense; those usually associated withthe spinothalamic system are pain, crudetouch, deep pressure, and temperature. Fibers in both the dorsal columns and thespinothalamic tract can respond to lighttactile stimulation, noxious stimulation, orboth light tactile and noxious stimulation. Sensory fibers do not distribute randomly inany part of the nervous system, but orderthemselves in such a way as to preservespatial information in their position; this issomatotopic organization. Dermatomes arethe composite receptive fields of all primaryafferent fibers entering a given dorsal rootand knowledge of their distributions isimportant in physical diagnosis. Corticallesions do not abolish somatic sensation, butelevate thresholds and interfere with use ofsomatic information in solving problems. The gate control theory of pain suggests thatwhether pain is experienced in a givensituation depends upon the balance ofactivity between large myelinated

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mechanoreceptive fibers, and smallmyelinated and unmyelinated nociceptivefibers. An endogenous pain suppressionsystem has been suggested to involve theperiaqueductal gray matter, the raphemagnus nucleus and descending pathways tothe spinal cord. Pain relief does followstimulation at these sites, but the mechanismis still being studied. Pain has been treatedsuccessfully with drugs, surgery, and stimu-lation techniques.

Suggested Reading:

1. Angaut-Petit D: The dorsal columnsystem. II. Functional properties andbulbar relay of the postsynaptic fibresof the cat's fasciculus gracilis. ExpBrain Res 22: 471-493, 1975.

2. Basbaum AI, Fields HI: Endogenouspain control mechanisms: review andhypothesis. Ann Neurol 4: 451-462,1978.

3. Clark FJ: Central projections ofsensory fibers from the cat knee joint. JNeurobiol 3: 101-110, 1972.

4. Corkin S, Milner B, Rasmussen T: Somatosensory thresholds. Contrastingeffects of postcentral-gyrus andposterior parietal-lobe excisions. ArchNeurol 23: 41-58, 1970.

5. Dennis SG, Melzack R: Pain-signallingsystems in the dorsal and ventral spinalcord. Pain 4:97-132, 1977.

6. Friedman H, Nashold BS Jr, Somjen G:Physiological effects of dorsal columnstimulation. In Bonica JJ (ed):Advances in Neurology, Vol. 4, Pain.pp. 769-773, New York, Raven Press,1974.

7. Gybels J, Kupers R, Nuttin B:Therapeutic stereotactic procedures onthe thlamus for pain. Acta Neurochir

(Wien) 124:19-22, 1993.8. Iggo A (ed): Handbook of Sensory

Physiology, Vol II, SomatosensorySystem. Berlin, Springer, 1973.

9. Kaas JH: Topographic maps arefundamental to sensory processing.Brain Res. Bull. 44:107-112, 1997.

10. King RB: Principles of painmanagement. A short review. JNeurosurg 50:554-559, 1979.

11. Mazars G, Merienne L, Cioloca C: Effets des soi-disant stimulations de lasubstance grise peri-acqueductale. Neurochirurgie 25: 96-100, 1979.

12. Melzack R, Wall PD: Pain mechanism:a new theory. Science l50: 971-979,1965.

13. Nathan PW: The gate-control theory ofpain. A critical review. Brain 99: 123-158, 1976.

14. Nathan PW, Rudge P: Testing the gate-control theory of pain in man. J NeurolNeurosurg Psychiat 37: 1366-1372,1974.

15. Richardson DE, Akil H: Pain reductionby electrical brain stimulation in man. I.Acute administration in periaqueductaland periventricular sites. J Neurosurg47: 178-183, 1977.

16. Shealy CN: Six years' experience withelectrical stimulation for control ofpain, In Bonica JJ (ed): Advances inNeurology, Vol. 4, Pain. pp. 775-782,New York, Raven Press, 1974.

17. Trevino DL, Coulter JD, Maunz RA,Willis WD: Location and functionalproperties of spinothalamic cells in themonkey, In Bonica JJ (ed): Advances inNeurology, Vol. 4, Pain. pp. 167-170,New York, Raven Press, 1974.

18. Weinberg RJ: Are topographic mapsfundamental to sensory processing?Brain Res. Bull. 44: 113-116, 1997.

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19. Woolsey CN: Cortical localization asdefined by evoked potential andelectrical stimulation studies, InSchaltenbrand G, Woolsey CN (eds): Cerebral Localization andOrganization, pp. 17-26, Madison, WI,Univ of Wisconsin Press, 1964.