The Ventral Spinothalamic Tract and Other Ascending Systems of the Ventral Funiculus of the Spinal Cord FREDERICK W. L. KERR Section of Nezrrologic Surgery, Mnyo Foundntzon, Rochester, Minnesota 55901

ABSTRACT The ascending degeneration resulting from experimental lesions of the ventral funiculus of the spinal cord of Macaca mulatta has been studied using the Nauta technique and its variants. The ventral spinothalamic tract is shown to be an independent entity with respect to the lateral spinothalamic tract; its fibers are widely distributed in the ventral funiculus and it establishes connections with the brain stem and thalamus which are analogous but not identical to those of the latter. Its role in the relay of nociceptive input is discussed in view of the similarity in hodology of the two systems and i t is proposed that i t may be responsible for the failure of anterolateral cordotomy to control pain on a long term basis. Other ascending systems in the ventral funiculus include the spino-olivary and spino-reticular tracts, as well as minor connections to the N. of Edinger-Westphal, the red nucleus and the superior colliculus. The projections from the ventral quadrant of the spinal cord to the brain stem are almost entirely ipsilateral until the rostral mesencephalon is reached, at which level the N. of Darkschewitz receives both ipsilateral and crossed input; the magnocellular nucleus of the medial geniculate body receives a small contribution which is mainly ipsilateral. I n the thalamus the VPL receives predominantly ipsilateral projections while the input to the paralaminar nuclei is only slightly less pronounced contralaterally than ipsilaterally.

The organization of ascending pathways in the anterolateral quadrant and dorsal columns of the spinal cord is known in considerable detail. However, there is virtually no information on the ascending systems in the ventral funiculus, due in part to the technical problem of producing lesions limited to this area. This study sought to provide data on several points. First, is there in fact a ventral spino thalamic tract (V S.T.T.) distinct from the well known lateral spintothalamic system (L.S.T.T.); if a V.S.T.T. is clearly identifiable, what are its relationships to the L.S.T.T., are its connections similar and can inferences be drawn with regard to its functions? Second, what other ascending tracts lie in the ventral funiculus and, what are their locations and connec tions. A review of the literature of recent decades failed to uncover any reports on ascending degeneration resulting from lesions limited to the ventral funiculus. However, J.

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NEUR.,159: 335-356

the presence of a V.S.T.T. is generally accepted and the statement usually made is that it mediates touch and light pressure, as distinct from the L.S.T.T. which, all observers agree, is concerned with the relay of information on pain and temperature and some light touch. The V.S.T.T. is diagrammed either a s a medial continuation of the L,S.T.T. or a s a distinct bundle of fibers located near the ventral surface of the ventral funiculus, lateral to the midline fissure and reaching the vicinity of the exit zone of the ventral roots (Stookey, '43; Rasmussen, '52, Crosby et al., '62). The rostral course of the V.S.T.T. is unknown or i t is assumed to accompany the L.S.T.T. Brodal ('69) and Willis and Grossman ('73) include both tracts under the single term of spinothalamic, disregarding a separation into lateral and ventral components in view of the absence of reliable data. 1

Supported in part by grant 5995 from the N.I.N.D.S.

335

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FREDERICK W. L. KERR

Because of the persistent references to a V.S.T.T. a search of the literature was carried out in an effort to identify the origin of the concept. The first reference appears to be in a study by Probst ('02) on the lemniscal system in the brain stem. He reported having transected the ventral funiculus via an anterior approach through the occipito-atlantoid ligament in a dog and stated that ascending degeneration could be followed with the Marchi technique to the lateral nucleus of the thalamus. The following year Rothmann ('03) studied the degeneration following lesions of the cord made in the same manner as Probst in dog, cat, monkey, and one chimpanzee. He confirmed Probst's findings and concluded that the tract terminated in the lateral aspect of the thalamus with projections also to the superior colliculus, nucleus of the posterior commissure and to the lateral vestibular nucleus. In the present study lesions limited to the anterior funiculus, or parts thereof, and the ensuing degeneration are described. MATERIAL A N D M E T H O D S

Four adult monkeys (Macaca mulatta) were used. Operative procedures were carried out under deep pentobarbital anesthesia and with tracheal intubation. The latter is necessary in order to maintain a satisfactory airway at all times in a procedure in which trachea and esophagus must be retracted for adequate exposure of the deeper layers.

Operation The skin was incised longitudinally on the midline over the trachea. The right sternomastoid muscle was retracted laterally together with the carotid artery, jugular vein, vagus, and sympathetic trunks. The prevertebral muscles were stripped from the anterior surface of two vertebrae. Using an electrically driven spherical burr of 3 mm diameter a window was made in the right half of one vertebral body. When there remained only a thin layer of posterior cortical bone, this was removed carefully with a combination of a smaller burr and a dental pick. A n exposure of the posterior longitudinal ligament of approximately 5 x 4 mm was obtained in this way. A pedicled flap with its base hinged on the midline was then fashioned including posterior longi-

tudinal ligament dura and arachnoid; a large amount of C.S.F. flooded the operative field at this time and was removed by suction. The flap was kept retracted by means of a 00000 silk suture; an excellent view of the anterior surface of the cord was obtained from the anterior spinal artery to a point just lateral to the site of emergence of the ventral roots. The pia-arachnoid was incised with a No. 1 1 scalpel blade parallel to the anterior spinal artery for a distance of slightly over 1 mm. From the midpoint of this incision the membranes were then transected laterally as far as the ventral root exit zone. The surface of the anterior column was thus exposed for incision and the anterior spinal artery was retracted to the opposite side with a fine hook. In one animal a complete transection of the ventral funiculus was done. Using a No. 1 1 blade a transverse incision was made beginning at an anterior rootlet and ending in the median ventral sulcus. The depth of the incision was 2.25 mm and planned so a s to have a triangular shape with the base on the surface and the apex close to the anterior white commissure. No hemorrhage or other complications were encountered. The dural-ligamentous flap was reflected back into position and a pledget of oxidized cellulose was packed gently into the vertebral body defect and the incision was closed. Partial lesions of the funiculus were made in the other three monkeys. In two of these bilateral superficial incisions were made, while in the third animal the deep portion of the ventral funiculus was transected bilaterally, leaving the superficial half intact; this was done by inserting a fine right angled hook sharpened on one edge into the median fissure to a point just ventral to the anterior gray commissure and then rotating it and moving it up and down twice for a vertical distance of 1 mm. Survival periods of 7 to 1 4 days were used at which time the animals were reanesthetized deeply and perfused with Pease's 4% phosphate buffered (pH 7.25) paraformaldehyde. Blocks of the spinal cord and brain stem were made in the transverse plane and serial frozen sections were cut at 30 M , The sections from the block containing the lesion were stained by the Luxol Fast Blue

VENTRAL SPINOTHALAMIC TRACT

method; the sections rostra1 to the lesion were stained by the Nauta-Gygax ('54) method and by the Fink-Heimer techniques. The grading system used for describing degeneration is similar to that employed by Mehler et al. ('60) and ranges from 0 to 1 for a trace of degeneration through 1 + to 4 for estimated increasing density of terminal degeneration. Nuclei which are not listed in table 1 did not receive terminal degeneration unless otherwise stated in the text (e. g., superior colliculus, posterior hypothalamus). Selected sections from successive levels of the brain stem were drawn with the aid of a microprojector. The position of the tract and of areas of terminal degeneration was marked on the coverslip of the slide using a fine pointed pen and india ink; with care the area can be exactly covered and its position and size accurately and easily represented in the projection drawing. In the drawing heavy dots indicate fibers in passage while fine dots indicate preterminal and terminal degeneration.

+

+

RESULTS

No detectable neurological deficit resulted from the operative procedure in any ani-

337

mal. The lesions in the four monkeys are illustrated in figure 1 ; in monkey No. 427 the incision has destroyed the ventral funiculus almost completely on one side, there being a small area of sparing in its most dorsal aspect at the base of the ventral horn. The lesion reaches the medial aspect of the exit point of the ventral root, but does not impinge on the anterolateral quadrant at any point, and consequently does not involve any area occupied by L.S.T.T. fibers; there is a minimal invasion of the deep aspect of the contralateral ventral funiculus. The corresponding ascending degeneration will be described in detail. The lesions in the other three monkeys were purposely restricted to portions of the ventral funiculus. There are two lesions, one superficial (No. 442) and the other similar but deeper (No. 429) which have involved both sides and a third lesion which has spared the superficial half c# the funiculus while totally destroying the deep half bilaterally (No. 399). The degeneration resulting from these partial lesions of the ventral funiculus is not described in detail but is summarized in table 1 and is the basis for the attempt at localization of tracts.

Fig. 1 Projection drawings of the lesions (stipple) in the spinal cords of the four monkeys in this study.

338

FREDERICK W . L. KERR TABLE 1

Siimmtiry of mciin projections tind relative density of termintrl degeneration following lesions of the u ent m l f i r n ic ulir s Experiment 42 7

Nucleus

442

Right

Medial Acc. Olive Dorsal Acc. Olive Centralis Vent. Supraspin alis R etroambiguu s Lateral Reticular Int. N. Cajal Gigantocellularis Paragig. Dorsalis Paragig. Lateralis

++++ ++++ ++ +++ 0 ++ ++ ++++ ++ +

Gigantocellularis Facial Subcoer. Vent. Subcoer. Dors. Proc. Teg. Gris. Lat.

+++ + ++ + +++

Periaqued. Gray Cun eiformis Darkschewitz Edinger-Westphal

++ ++ +++ +

Med. Genic. MC Vent. P. Lat. Paralaminar Nuclei

+++ +++ +++

Left

0 O+ O+ 0 0

0

O+ O+ 0

0 0 0

O+

0

0 0 0 0 0

0 0 0

0 0' O f 0

++

O+

+ + +++

0

++++ ++++ + ++

+++ 0 + 0 ++ +

0

++

+ ++ ++

+

O+ O+

0

+ +

Medulla The ascending degenerated fibers form a conspicuous superficial group along the lateral aspect of the pyramid until the medial accessory olive appears and displaces

+

0 0

+ + +

0

O f

Di enc eph alon 0

+ +

0

0

trace of degeneration;

Spinal cord In the segments rostra1 to the cordotomy, degeneration was most marked in the medial aspect of the ventral horn both ipsi and contralaterally. No degeneration entered the dorsal horn, but in all the experiments there was a mild scatter of terminal degeneration in the periependymal gray substance on both sides. The intermediate nucleus of Cajal received a moderate ipsilateral contribution. Small numbers of fine fibers were seen crossing in both the ventral gray and the most dorsal aspect of the dorsal gray commissure.

++

0

Mesencephalon 0 0 O f

0

+

399

Right

Medulla

++++ 0 + 0 ++ + ++ + + 0 0 0 O f

+,

Left

Pons

+

Key to symbols: 0, no degeneration; 0 and/or extent.

Right

+

0

429

to

Left

Right

++++ ++++ ++++ ++++ 0 +++ ++ +++ +

++ ++++ + + ++ + 0 +++ +++ ++

0

+++ ++ + +++

O+

++ ++ ++ +

+ ++ ++

+ + + 4- , clear degeneration

+ + +

0

o+

+ ++ +

0

+++

+++ +++

Left

O+

++ + + + 0 ++ ++ 0

O+ O+ 0 O f O f 0 O f

0

+ + + + +

of increasing density

them further laterally (fig. 2A). Throughout this part of their course fibers can be seen leaving the main contingent to enter the N. supraspinalis; a moderate number are distributed to the ventromedial aspect of the lateral reticular nucleus. The N . retroambiguus was free of degeneration except for the experiment (No. 399) in which the deepest part of the ventral funiculi was transected; in this instance moderate degeneration was present. Moderate numbers of fibers enter N. centralis ventralis but none are seen in centralis dorsalis or parvocellularis. A small cluster of degenerating fibers i s seen in the ophthalmic area of the spinal nucleus of the trigeminal just below the plane of the obex. The medial accessory olive showed dense terminal degeneration in its caudal ventrolateral tip and on ascending further, (fig. 2b) there is a profuse contribution to the

VENTRAL SPINOTHALAMIC TRACT

339

dorsal accessory olive where it is distributed they descend to reach the cerebellum. to all but its medial third. No degenerating Some of the latter fibers end in the roof nuendings are seen in the principal olivary clei where they are seen in small numbers nucleus. in the fastigial nucleus ipsilaterally and ocLarge numbers of degenerated fibers are casionally in the contralateral homologue. seen running into and terminating in the An occasional degenerating “en passage” N. gigantocellularis; the N. paragiganto- fiber is also seen in the N. interpositus, but cellularis dorsalis (interfascicularis hypo- not in the dentate nucleus. glossi) receives a moderate contribution, (fig. 4) while the N. paragigantocellularis Mesencephalon lateralis receives only scattered fibers. The ascending fibers are seen in the dorA few degenerating fibers are present solateral tip of the medial lemniscus, coursin the medial and lateral vestibular nu- ing progressively more dorsally a s higher clei; none were present in the solitary nu- levels are reached (fig. 2E). At the level cleus or in the N. of Roller. There were no of the medial geniculate body they pass contralateral connections and it should be along its medial aspect and give a small noted that throughout the terms contra and but dense contribution to its magnocellular ipsilateral are with reference to the lesion subdivision (figs. 2F, 5). in the spinal cord and do not refer to the At the level of the colliculi, fibers course neurons of origin. medially from the tract and, passing through the N . cuneiformis to which they Pons appear to give a moderate but quite wideThe V.S.T.T. which in the medulla oc- spread contribution (figs. 2E,F, S), reach cupied a position just lateral to the inferior the lateral and ventrolateral aspect of the olive where it was intermingled with the rostral portion of the periaqueductal gray L.S.T.T., separates quite abruptly from it substance (PAG). The fibers which reach the lateral aspect in the ponto-medullary transition area, passes around the medial aspect of the su- of the PAG enter and scatter through the perior olivary complex and travels rostrally subnucleus lateralis just medial to the mesalong the dorsal surface of the latter (fig. encephalic nucleus of V (fig. 7). At more 2c). It subsequently passes further lateral- rostral levels a contingent of fibers enters ly, (fig. 2d) and again ascends in close re- the PAG from its ventrolateral aspect and lationship to the L.S.T.T. to its termination forms a fairly conspicuous terminal network in the N. of Darkschewitz (figs. 2F,G, in the thalamus. The distribution of terminal degenera- 8); the latter is clearly outlined in this way tion in the low pons continues to be much even in sections in which it is cytologically the same a s in the medulla, with a marked poorly defined. This projection is mainly contribution to the N . gigantocellularis, ipsilateral and is present at all levels of the (fig. 2c) none reaching the N. reticularis nucleus. No degenerating fibers are seen parvocellularis or the N. pontis caudalis; a entering the interstitial nucleus of Cajal, few degenerated fibers may occasionally be but occasional degenerating fibers are seen seen in the ventromedial aspect of the fa- in and in the vicinity of the N . of Edinger Westphal (fig. 9). The red nucleus receives cial nucleus. At mid and rostral pontine levels the a small projection which is limited to its same pattern of degeneration continues, the rostral and dorso lateral quadrant (fig. 10); only additional feature being a modest pro- this is present bilaterally but is more evijection to the Processus tegmentous griseus dent in the ipsilateral side. A few degenerating fibers are seen in lateralis and moderate degeneration in the N. subcoeruleus ventralis; a mild scatter of the deep stratum of the superior colliculus; degenerating fibers is also seen in the N. none enter the inferior colliculus. No degenerating fibers are seen in the subcoeruleus dorsalis (fig. 2d). A few fibers pass laterally to the de- nucleus of the posterior commissure. scending tract of V and, continuing dorsally, pass over the dorso-lateral aspect of Diencephalon the superior cerebellar peduncle to reach The V.S.T.T. after passing along the the anterior medullary vellum in which medial aspect of the medial geniculate nu-

Abbreviations

C M., N. centrum medianum Cn S, N. centralis superior Cn V, N. centralis ventralis medulla C P, posterior commissure Col. S., superior colliculus Cu m, N. cuneatus medialis Cun, N. cuneiformis Da, N. of Darkschewitz De Pe Ce S, decussation superior cerebellar peduncles G. C., N. gigantocellularis Gr., N. gracilis H., field H of Fore1 Hab., N. habenulae L. G., lateral geniculate Le l., lemniscus lateralis Le m, l e m n i x u s medialis L. P., N. lateralis posterior L. R., N. reticularis 1at er ali s

M. D. pc, N . medialis dorsalis (parvicellularis) M. Th., T. mammillothalamicus Mm., N . mammillaris M. G. m, medial geniculate (pars magnocellularis) Om, medial accessory olive 0 1 S, superior olivary complex P A G, periaqueductal gray Pc, N. parvocellularis medulla Pe Ce S, superior cerebellar peduncle Pe Ce m, middle cerebellar peduncle Ped, pes pedunculi Pf, N. parafascicularis Pi, pineal P1, N. paragigantocellularis lateralis Po, N. pontis caudalis Po 0,N. pontis oralis

Pul, pulvinar Pul 0,N . pulvinaris oralis Pyr., pyramidal tract Ru, N. ruber S, T. solitarius Scd, N. subcoeruleus dorsalis Scv, N. subcoeruleus ventralis S Cun, N. subcuneiformis S th., N. subthalamicus Su n , substantia nigra V.P.L.C., N. ventralis posterolateralis (caudalis) V.P.M., N. ventralis posteromedialis N 111, nucleus oculomotorius Vs, T. spinalis trigemini N V, nucleus spinalis trigemini VI, nucleus abducens VII, nucleus facialis VIII m, nucleus vestibularis medialis VIII c, N. cochlearis ventralis

Fig. 2 Projection drawings of the ascending degeneration which resulted from transection of the ventral funiculus at C4.Tract fibers are represented by heavy stipple and terminal degeneration by fine stipple; description in text.

34 1

VENTRAL SPINOTHALAMIC TRACT

cleus continues further dorsally among the cells of the suprageniculate nucleus and, as it enters the caudal aspect of the diencephalon, separates into two branches. The medial branch first sends a small number of fibers to the ipsilateral postero-medial hypothalamus (figs. 2G, 11). These fibers run in a dorsal to ventral direction and can be readily followed ventrally to the N. of Darkschewitz which is still readily identifiable at this level due to the bilateral projections to it described earlier. In addition to these fibers to the posterior hypothalamic nucleus, small numbers of fibers of fine caliber are distributed to the ipsilateral posterior periventricular gray, that is to say the area dorsomedial to the posterior hypothalamic area. In one experiment (the total transection) there was a small but quite pronounced cluster of terminal degeneration in the N. centralis inferior, more evident ipsilaterally but having some contralateral projections also. The medial branch of the V.S.T.T. continues rostrally just lateral to the habenulo-interpeduncular tract and runs along the medial medullary lamina of the thalamus to end in a conspicuous cluster of terminal degeneration in the paralaminar nuclei as defined by Mehler et al. (‘60) (subnuclei multiformis and densocellularis of the N. medialis dorsalis of Olszewski’s classification); a small number of fibers were seen terminating in the subnucleus parvocellularis in some sections (fig. 2G) in experiment 427 but not in the other experiments. Interestingly, the nuclei of the lamina itself (centralis lateralis and paracentralis) do not receive any terminal degeneration. The projections to the paralaminar nuclei are bilateral and of equal density on each side (figs. 12, 13); a small but distinct projection is also seen reaching the N . centralis superior lateralis in some sections, again only in experiment 427. There was no degeneration in the N. parafascicularis or in the N. centrum medianum though degenerating fibers passed through the latter and the dorsomedial aspect of its capsule. The lateral branch of the V.S.T.T. leaves the rostral mesencephalon by coursing transversely into the field H1 of Fore1 to reach the N. ventralis posterolateralis pars caudalis where it ends in small “bursts” in the same manner described by Mehler et al.

(‘60),for the L.S.T.T. In its lateral course a few fibers appear to leave it to enter the zone incerta (fig. 2G); whether they terminate in the latter could not be established. The projection to the N. ventralis posterolateralis is both ipsi and contralateral, the latter being much less marked than the former. It was not possible to determine the course of the crossed component and for this reason it is represented by a n interrupted line in figure 3 which summarizes the course and main connections of the ascending systems of the ventral funiculus.

Decussations Fibers can be seen entering commissural systems at various levels, but always in small numbers. In the spinal cord they are present in both dorsal and ventral gray commissures rostral to the spinal lesion and a few fibers cross in the commissure of the superior colliculus and in the posterior commissure. Experiment 427 in which the lesion was almost exclusively unilateral, emphasizes the predominantly ipsilateral nature of the ascending projections of the ventral funiculus to the brain stem until mesencephalic and diencephalic levels are reached, where crossed projections appear for the first time and end in the N. of Darkschewitz, the VPL and the paralaminar nuclei (fig. 2, table 1); it is again noted that ipsilateral refers only to the ventral funiculus and not to the location of the cells of origin of the tracts. DISCUSSION

The existence of a V.S.T.T. separate from the well known L.S.T.T. has never been satisfactorily resolved. A s noted earlier, the evidence for a V.S.T.T. is fragmentary and inconclusive and, in general, almost nothing is known regarding ascending tracts in the ventral funiculus. The present experiments indicate that this portion of the spinal cord contains a number of ascending systems which reach all levels of the brain stem including the mesencephalon and thalamus. It is interesting to note that these ascending connections are similar in many respects to those of the anterolateral quadrant of the cord and that the connections of the L.S.T.T. are replicated in almost every way by the V.S.T.T. which has some

342

FREDERICK W. L. KERR

additional connections not present in the former. Probst’s (’02) lesion was located in the spinal cord just below the pyramid and had transected the left ground bundle as far as the anterior horn; since it was not illustrated, comparison of results is somewhat uncertain, particularly if the anterolateral quadrant of the cord was involved also. The course of the tract as he reported it was comparable to that seen in the present study, though he did not note that it passed dorsally to the superior olivary complex and, because of the limitations of the Marchi technique, many of the connections now revealed by the Nauta method were not observed, while some connections (to the lateral vestibular nuclei for example) appear to have been due either to species differences (Mehler, ’69) or to artefacts, since they are of neglible proportions in the present experiments. He observed the contribution to the N. gigantocellularis of the medulla and pons and commented that he could not be certain regarding connections to the magnocellular component of the medial geniculate nucleus, but clearly the possibility was considered. At the thalamic level terminal, degeneration was limited to the ventrolateral nucleus. Rothman’s (’03) studies, as noted earlier, confirmed Probst’s observations and added a number of connections which appear to have been artifactual or due perhaps to extensive damage to the cord, since he stated that his animals were quite severely ataxic, whereas the present observations indicate that complete transection of the ventral funiculus is not associated with any objective evidence of motor deficit. The possibility of confusing fibers of the Fig. 3 Schematic representation of the course and connections of the main ascending systems of the ventral funiculus. T h e asterisk at the pontine level indicates the position of the lateral spinothalamic tract which is separated from the V.S.T.T. by the superior olivary complex. 1, dorsal (and ventral) accessory olives. 2 , lateral reticular nucleus. 3,N. gigantocellularis medullae. 4, N. paragigantocellularis dorsalis. 5, N. gigantocellularis pontis. 6 and 7, Nn. subcoerulei ventralis and dorsalis. 8 and 14,N. cuneiformis. 9, subnucleus lateralis of periaqueductal gray. 10, magnocellular N. of medial geniculate N. 1 1 and 17, N. of Darkschewitz. 12,N. of Edinger Westphal. 13, Red.N.15, N. ventralis posterolateralis. 16, N. medialis dorsalis p. densocellularis and multiformis. 18, posterior hypothalamic area.

V E N T R A L SPINOTHALAMIC T R A C T

L.S.T.T. with those of the V.S.T.T. in lesions at the spinal cord level must be considered in view of the diagrams of Hyndman and van Epps (’39) and of Walker (’40) which show the medialmost fibers of the L.S.T.T. lying in a position ventromedial to the ventral roots in their course through the white matter. This source of error was excluded in this study because on the one hand, three of the four lesions (Nos. 427, 442, 399) completely spared the area where the most medial fibers of the L.S.T.T. are diagrammed by these authors and, on the other hand, the two tracts can be readily distinguished at the pontine level where they are separated by the superior olivary complex, a position that was confirmed in each of the four experiments reported here. The connections and functional significance of the ascending fiber systems of the ventral funiculus are of particular interest with regard to central transmission of nociceptive input in view of the similarity of the V.S.T.T. to the L.S.T.T. Significance of the V.S.T.T Before discussing this tract it is necessary to establish what components are to be regarded as belonging to the V.S.T.T. itself and which are unrelated but ascend in close association with it. In some instances this differentiation is readily made, as in the case of the spino-olivary tracts for example, which are functionally not related though invariably transected when the spinothalamic systems are severed. The spinoreticular input appears to be predominantly, or possibly exclusively, of ipsilatera1 origin in the cord (Kerr and Lippman, ’73, ’74); this suggests, but does not prove, that the bulbar reticular formation is not concerned with nociceptive mechanisms and, in this respect, the observations of Casey (’69) and of Casey et al. (‘74) must be considered. They have found neurons in that area which respond strongly to noxious stimuli and also, that stimulation of the same area leads to escape behavior. This issue will be discussed in more detail in a forthcoming report. The crossed systems, with the exception of the spino-olivary tracts, have few connections to the medulla and pons as demonstrated by the experiments referred to above in which degeneration was traced after uncomplicated midline myelotomy

343

had been performed. It is only when the mesencephalon is reached that any significant crossed spinal projections begin to terminate. Whether all such connections are to be regarded as dependencies of the spinothalamic tract or not cannot be stated in a definitive manner, but there is a significant volume of evidence from physiological studies to suggest that most of the nuclei at this level and rostrally which receive crossed spinal input are concerned with either nociceptive mechanisms or with modalities such as light touch mediated by the spinothalamic system. Whether these connections to mesencephalic and diencephalic nuclei are established by collaterals or by separate fibers running to each nucleus is also a n issue which has not been settled; however, it would seem likely, in view of the relatively small number of spinothalamic fibers which are present a t the mesencephalic level (Glees and Bailey, ’51), that most of the connections between that plane and the termination in the thalamus are provided by collateral branches of the tract. Mesencephalon The two main connections to be considered here are those to the N. cuneiformis and to the PAG area; in addition, the projection to the N . of Edinger-Westphal is of interest. The N. cuneiformis of Olszewski and Baxter (’54) is coterminous with the rostrocaudal extent of the colliculi and, though it is one of the less obvious subdivisions of the mesencephalic reticular formation, it is of interest because of its possible relationship to nociceptive integration. The present study suggests that it receives a low density diffuse network of fibers from the spinal cord; what proportion of these fibers terminate in the nucleus relative to the number of fibers which are “en passage” to the PAG is difficult to determine. However, a significant number run in an irregular and haphazard manner through the nucleus and evidently are not directed to the PAG; since many appear to not travel beyond the confines of N. cuneiformis it seems reasonable to conclude that they terminate within it. Ascending degeneration following midline myelotomy also leads to similar fiber degeneration in the N. cuneiformis, thus favoring a crossed

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FREDERICK W. L. KERR

nature of spinal input to this area (unpublished observations). The projections to the PAG appear first at the plane of the inferior colliculus and, as noted, are limited at this level to the subnucleus lateralis. This connection ceases when the N. of Darkschewitz appears and degeneration is present in the latter as far as its termination at the level of the posteromedial hypothalamus. Thus, from a lateral position caudally, the spino-annular projections become ventrolateral at more rostra1 levels where they are located on the border between the central gray and the mesencephalic reticular formation. Spinal projections to the PAG were first described by LeGros Clark ('36) and confirmed by a number of investigators since then (Johnson, '54; Mehler, '57; Bowsher, '57; Mehler et al., '60; Mehler, '69). This projection was uniformly described as ending in the lateral aspect of the PAG but input from the spinal cord to the N. of Darkschewitz was not reported. From a functional standpoint there is considerable evidence, both in animals and man, that the PAG is significantly concerned with nociceptive mechanisms. Magoun et al. ('37) showed, both in the cat and the monkey that stimulation of the PAG over a long caudo-rostral extent resulted in cries, screeches and barks associated with grimacing, increases in respiratory rate, pupillodilatation, urination and struggling, all of which suggested activation of a system concerned with pain. Furthermore, the area from which these responses could be obtained extended into the tegmentum lateral to the PAG at the level of the superior colliculi; this area corresponds to the N. cuneiformis as depicted in the atlas of Olszewski and Baxter ('54). In fact the loci from which behavioral responses suggestive of nociceptive activation are elicited superimpose almost exactly with the degeneration pattern in the mesencephalon nuclei as observed in this study. It is important to note also, that none of the points from which the nociceptive responses were obtained were situated in the area occupied by the spinothalamic tracts themselves. Further evidence that the PAG and adjacent dorsolateral tegmentum is concerned with pain mechanisms has been provided by the investigations of Spiegel et al. ('54), Halpern ('68), Hunsperger ('56), Reynolds

('69), Liebeskind and Mayer ('70) and Liebman et al. ('70) who have shown that responses indicative of nociceptive activation or, interestingly, the production of analgesia, can be elicited by electrical stimulation of this zone. Some discrepancy in the rostrocaudal extent of the area from which these effects can be obtained is noted; thus Magoun et al. ('37) and Spiegel et al. ('54) describe it as extending the entire length of the PAG whereas in the more recent studies, the effects were obtained from more caudal levels. Of particular interest are the studies of Nashold et al. ('69a,b) in which both stimulation and lesion studies of the mesencephalon were carried out in conscious patients. They showed that stimulation of the PAG elicited pain and burning sensations referred to the center or core of the body, associated with strong emotional effects and autonomic reactions, while stimulation of the tegmentum lateral to the PAG evoked noxious sensations (pain, burning) referred to the contralateral half of the body with a much less pronounced emotional response. Lesions which they placed in the dorsolateral mesencephalic tegmentum at the level of or below the posterior commissure produced satisfactory relief in 11 of 15 patients suffering from severe intractable pain. The cumulative evidence from anatomical investigations which show that both the L.S.T.T. and the V.S.T.T. project into the N. cuneiformis and the lateral PAG and from physiological studies in animals and man, indicates that the area is concerned with nociceptive mechanisms and supports the view that this is an important and possibly the first level of integration for pain, a suggestion that was first made by Walker ('43). The reciprocal connections between the PAG and areas such as the orbitofrontal cortex (Beyer et al., '62) and the hypothalamus, (Guillery, '57; Nauta, '58; Cowan et al., '64; Olds and Frey, '71) whose roles in affective responses including those to pain are recognized as described at a later point, are in good accord also with the concept of this being an important integrative center for the emotional aspects of nociception.

N.of Edinger Westphal Reflex dilatation of the pupils is one of

VENTRAL SPINOTHALAMIC TRACT

several autonomic phenomena associated with noxious stimulation; for a detailed review the reader is referred to the article by Loewenfeld (’58). Two ascending systems from the spinal cord have been shown to mediate this response in the cat (Loewy et al., ’73). One of these could be activated by electrical stimulation of the area of the lateral spinothalamic tract in the brain stem but no evidence of degeneration ending in the N. of Edinger-Westphal has been reported in studies in which this tract has been transected in the spinal cord and in our own anterolateral cordotomy material in the monkey there has likewise been no sign of degeneration in this nucleus. However, when the ventral funiculus was transected a few fibers could be seen in almost every one of serial sections through this nucleus; degenerating pericellular baskets were not present, again raising the issue of actual terminating or “en passage” nature of these fibers, but since they could not be followed beyond the confines of the nucleus, it is concluded that they most probably do terminate within it. Reference to table 1 indicates that in the spinal cord these fibers appear to be confined to the intermediate or deep layers of the anterior funiculus. Dienc ephalon The V.S.T.T. projection to the magnocellular component of the medial geniculate nucleus (MGm) is small and consists of one to three small “bursts” of terminal degeneration. There was no evidence of degeneration in the closely associated N. suprageniculatus or other cell groups belonging to the PO complex. A detailed discussion of the area is not appropriate in view of the paucity of input to it from the V.S.T.T. The projection of the V.S.T.T. to the VPL is similar to that established by the L.S.T.T. both in terms of the area of termination and the terminal “bursts” which are characteristic of the extralemniscal projections (Mehler et al., ’60). The question of a somatotopic organization at this level for the V.S.T.T. has not been examined in this study but it would seem probable that it does exist. Finally it should be noted that the density of V.S.T.T. projections to VPL is considerably smaller than from the L.S.T.T. The connections of the V.S.T.T. to the

345

medial thalamus differ in several respects from the corresponding L.S.T.T. projections. The V.S.T.T. sends no fibers to the N. centralis lateralis whereas L.S.T.T. projections to this nucleus are well established (Mehler et al., ’60; and others). The connections of L.S.T.T. to the paralaminar portion of the N. medialis dorsalis (NN. densocellularis and multiformis) are replicated by the V.S.T.T. and in addition, in some sections the subnucleus parvocellulark of MD received a scatter of terminals from the V.S.T.T. The centrum medianumparafascicular complex did not appear to receive any input from the V.S.T.T.; this is comparable to the observations on the L.S.T.T. made by Mehler et al. (’60) and Mehler (‘69). The presence of degenerating fibers in the posteromedial aspect of the hypothalamus is of interest in view of suggestions which have been made that the hypothalamus may participate in pain mechanisms. Karplus and Kreidl (’28) were the first to present evidence that stimulation of the hypothalamus elicited responses suggestive of noxious activation and Spiegel et al. (‘54) have proposed that the hypothalamus may play a significant role in the Dejerine-Roussy thalamic syndrome. In a recent report Olds and Frey (’71) have reported that lesions throughout the medial hypothalamus and in the middle or posterior lateral hypothalamus are effective in blocking escape reactions elicited by stimulation of the PAG in rats. These observations together with the evidence of a minor direct input from the spinal cord to the posteromedial hypothalamus, suggest that this area may be activated both monosynaptically via the latter projection and polysynaptically by way of the spino-annular connections. Clinical neuroanatomy The control of intractable pain by transection of the L.S.T.T. in the anterolateral quadrant of the cord has been highly successful on a short term basis, that is to say, for periods of six months to a year (White and Sweet, ’69; White, ’63). Return of pain after this period has limited the usefulness of this otherwise excellent procedure to patients with short life expectancy. The reasons for the return of pain have not been clarified and various possibilities

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FREDERICK W. L. KERR

have been proposed. Regeneration of transected fibers or crush injury without actual transection of the axons have been suggested by White and Sweet. However, secondary and even tertiary cordotomies at higher levels have generally been unsuccessful in alleviating recurrent pain (White, '63). Furthermore, anterolateral cordotomy elevates the threshold for pain some 40 or 50% (King, '57; Papo and Caruselli, '70) but does not abolish pain sensation. It is also of interest that certain types of pain are either unaffected by this procedure or only partially improved. Since cord transection abolishes all somatic pain sensation below the level of the lesion, it is evident, therefore, that a significant alternate pathway for nociceptive relay to higher centers must be present in the cord in an area other than the anterolateral quadrant. In this respect, Schiff (1854) over a century ago believed that pain transmission occurred via fibers which ascend in the gray columns of the cord; this alternative was also considered by Mott (1895) for example and recently by Basbaum ('73). In myelotomy material I have specifically looked for degenerating fibers ascending in the gray matter above the level of the lesion; myelinated fibers of very small caliber were seen in the dorsal gray with characteristics of degeneration, but they were so infrequent that it is doubtful that they are significant. The possibility that unmyelinated fibers, which are abundant in the spinal gray, may play some role in the relay of pain to higher levels cannot, however, be completely ruled out. Also, consideration should be given to the possibility of complex crossing of the afferent system in the gray substance of the cord, particularly in the rat (Basbaum, '73). The possibility of significant species differences in the organization of spinal pathways of primates and subprimates is emphasized by reports such as that of Jane et al. ('64) on motor function in the cat with hemisection of the spinal cord. The demonstration that the anterior funiculus contains another independent spinothalamic tract with all the connections at rostra1 levels which are known for the L.S.T.T. with some additional projections to areas concerned with nociception

that are not projected on by the L.S.T.T. provides a new anatomical basis for the relay of nociception by pathways outside of the anterolateral funiculus; the latter is defined as that portion of the white matter extending from the insertion of the dentate ligament on the cord to the exit of the medialmost ventral root filaments and in depth to the gray substance. If, as is proposed here, the ventral spinothalamic tract relays nociceptive input in addition to tactile and pressure sensations, the satisfactory short term results of anterolateral cordotomy which transects the L.S.T.T. must be accounted for. While a definitive answer cannot be given at this time, it was noted above that anterolateral cordotomy produces an elevation of threshold but not abolition of pain sensation below the level of the lesion. It may well be that transection of the L.S.T.T. is sufficient to abolish the level of nociceptive input produced by metastatic and other disease syndromes which are responsive to this type of surgery or, in other words, the afferent nociceptive barage they provide is within the 40 to 50% elevation of threshold provided by tractotomy of the L.S.T.T. Possibly, the subsequent breakthrough of pain six or more months after a successful cordotomy result is due to increase in nociceptive input relayed via the V.S.T.T. as the pathologic process progresses. Failure to relieve pain by additional incisions of the anterolateral column would be due to the far medial position of the V.S.T.T. which has a significant proportion of its fibers in the depths of the ventral funiculus. The possibility that specific types of pain sensation may be preferentially mediated by one or the other spinothalamic tract may also be considered. Thus, transection of the L.S.T.T. is particularly effective in controlling the pain of metastatic malignancy and in certain forms of neuralgia, but results are much less satisfactory in postherpetic neuralgia, in pain of tabetic crises, in phantom limb, in root avulsion pains and in pain of visceral origin. It is possible that these varieties of pain are relayed predominantly by the ventral spinothalamic tract. The significantly better results obtained by White and Sweet ('69) in pain of this type may be due to their earlier recognition

VENTRAL SPINOTHALAMIC TRACT

of the fact that the classical dictum that the cordotomy incision should reach only as far as the level of emergence of the motor rootlets from the cord is often unsatisfactory and that an incision carried further medially may be more effective. In fact, a major portion of the spinothalamic system will be missed by a “classical” incision, and even if the incision is extended well medially to the ventral root exit zone, with the corresponding possibility of damage to the anterior spinal artery, the majority of the spinothalamic fibers of the ventral funiculus will still be unaffected since they are located more deeply in the ventral funiculus. It should also be remembered that Hyndman and van Epps (’39) advocated transecting the ventral funiculi as well as the anterolateral quadrant for control of pain.

Other ascending tracts of the ventral funiculus (VF) In view of the similarities in their course and connections to those of the anterolatera1 quadrant (ALQ) which have been reviewed in detail by Mehler (’69) they can be discussed briefly. Whereas the V.S.T.T. has characteristics such as divergence in course and some difference in connections with the L.S.T.T., the spino-olivary system of the VF terminates in the same portions of the medial and dorsal accessory olives as the tract located in the anterolateral quadrant (ALQ), the only difference being that the projections from the VF to the dorsal accessory olive reach further medially. It would seem appropriate therefore to consider the spinoolivary tract to be a single fairly extensive system of fibers which occupies both the VF and the ALQ and there would be no reason to suggest dividing it into lateral and medial components. Spinoreticular projections of the VF (table 1) are also similar in almost all respects to those of the ALQ the only obvious difference being their lesser abundance. With regard to their.functiona1 role, this subject has been discussed briefly in a recent report (Ken and Lippman, ’74) in which it was noted that most of these connections appear to originate in the ipsilateral spinal gray and are, therefore, unlikely to be concerned with pain mechanisms.

347

Minor connections Facial nucleus Spinofacial fibers were first described by Johnson (’54) and by Nauta and Kuypers (’58) in the cat and by Mehler (’57, ’60, ’69) in the monkey following anterolateral cordotomy as low as C7. Mehler (’69) reviewed the subject in detail and pointed out that the spinal input to the facial nucleus reached the phyletically old medial and ventral component and that the density of input from spinal sources becomes progressively weaker with ascending phylogenetic development. In this study the few degenerating fibers observed in the facial nucleus were also located in its ventromedial aspect; recently, electrophysiological evidence for monosynaptic activation of facial neurons following stimulation of the lateral funiculus of the spinal cord has been reported by Tanaka et al. (’71).

Cerebellar nuclei Considerable doubt had prevailed regarding direct spinal projections to the cerebellar nuclei. However, Mehler (’69) describes bilateral projections to the fastigial nuclei following anterolateral cordotomy in all the species he investigated. These arise as collaterals from the ventral spinocerebellar tract and have been discussed by Eccles et al. (’67). The input from the ventral funiculus is of very minor proportions and reaches the cerebellum in the same manner as the V.S.C.T. It seems likely that this is not a separate connection but due only to interruption of the most medial fibers of the V.S.C.T. Localization of tracts in the ventral funiculus One of the objectives of this study was to try to determine whether the ascending systems of the V.F. are parcellated into well delimited areas; it was hoped that the combination of superficial, deep and complete transection would resolve this point. Table 1 indicates that this hope was only partially realized; the following comments are to be regarded only a s an approximation. The superficial aspect of the V.F. contains almost no fibers of the spinothalamic system a s shown by the paucity of input to nuclei rostra1 to the medulla in experiment

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FREDERICK W. L. KERR

442; this is in marked contrast to what would have been expected from the diagrams in those standard texts which indicate that the V.S.T.T. occupies a superficial position along the ventral surface of the funiculus, as noted earlier. The largest concentration of V.S.T.T. fibers appeared to be present in the deep and intermediate layers of the V.F. (Exp. 399). Fibers to the dorsal accessory olive were apparently present in all layers of the V.F., though the medial accessory olive fibers appeared to be confined to the intermediate stratum (Exps. 427, 442, 429, 399). Spino -reticular fibers were present throughout the V.F. The degeneration pattern for experiment 427, summarized in table 1, emphasizes the ipsilateral pattern of projection to medulla and pons following a lesion confined to one V.F. and the bilaterality of connections to mesencephalic and especially, diencephalic levels. Also, it is noted that the results obtained in experiment 429 must be regarded with caution, since it clearly involves the medial aspect of the anterolateral quadrant. The conclusions reached are, as noted earlier, based primarily on the experiments which affected the V.F. alone, either totally or in part. Summary The V.S.T.T. is a system of fibers distributed throughout the ventral funiculus of the spinal cord. Its course and connections are very similar to those of the L.S.T.T. but it is of considerably smaller volume than the latter. Based on preliminary studies of midline myelotomy material (Kerr and Lippman, ’74) its input-as distinguished from that of the ventral funiculus - to the reticular nuclei of the medulla and pons is probably of minor proportions. The main connections can be summarized as follows. In the mesencephalon and diencephalon it divides into lateral and medial “currents.’’ The lateral component provides small dense clusters of terminal degeneration to the magnocellular part of the medial geniculate nucleus and to the n. V.P.L.; some very minor crossed projections to the same nuclei are present. The medial projections are to the periaqueductal gray where the ipsilateral subnucleus lateralis receives input 0ver.a short

caudo-rostra1 distance at the level of the inferior colliculus; thereafter the P.A.G. projection is limited to the n. of Darkschewitz which receives mainly ipsi as well as contralateral projections. A diffuse low density projection appears to end in the ipsilateral n . cuneiformis. In the thalamus bilateral projections reach the paralaminar nuclei but do not end in the nuclei of the lamina itself. It is suggested on the basis of the connections made by these two ascending fiber “currents” and the extensive studies on stimulation and ablation in the literature, that the medial component of the V.S.T.T. is concerned mainly but not exclusively with the affective motivational aspects of nociception and that the lowest level of integration is in the mesencephalon. The lateral component of the V.S.T.T. should be related mainly to discriminatory function in view of its projections to VPL, but in addition it may mediate nociceptive input via its connection to MGm. The similarities between the ascending projections of the ventral funiculus and those of the anterolateral quadrant of the lateral funiculus extend also to the spinoolivary and spinoreticular tracts. Some minor connections are limited exclusively to the ventral funiculus and include those to the N. of Edinger-Westphal, to the N. of Darkschewitz, red nucleus, posteromedial hypothalamus and N . centralis superior lateralis of the thalamus. LITERATURE CITED Basbaum, A. 1973 Conduction of the effects of i ~ o x i o u sstimulation by short-fiber multisynaptic systems in the spinal cord of the rat. Expl. Neurol., 40:699-716. Beyer, C., J. S. Tindal and C. H. Sawyer 1962 Electrophysiological study of projections from mesencephalic central gray matter to forebrain i n the rabbit. Expl. Neurol., 6: 4 3 5 4 5 0 . Boivie, J. 1971 T h e termination of the spinothalamic tract in the cat. An experimental study with silver impregnation methods. Expl. Brain Res., 12: 331-353. Bowsher, D. 1962 The topographical pro.jection of fibers from the anterolateral q u a d r a n t of the spinal cord to the sub-diencephalic brain stem in man. Psychiat. Neurol. Basel., 1 4 3 : 75-99. Brodal, A. 1969 Neurological Anatomy in Relation to Clinical Medicine. Second ed. Oxford University Press, New York, London, Toronto. Casey, K. L. 1969 Somatic stimuli, spinal pathways and size of cutaneous fibers influencing

VENTRAL SPINOTHALAMIC TRACT unit activity in the medial medullary reticular formation. Expl. Neurol., 25 : 35-36. Casey, K . L., J. J . Keeney and T. Morrow 1974 Bulboreticular and medial thalamic unit activity in relation to aversive behavior and pain. I n : Advances in Neurology. J. J. Bonica, ed. Raven Press, New York, pp. 197-205. Clark, W. E. LeGros 1936 T h e termination of ascending tracts in the thalamus of the macaque monkey. J . Anat. (London), 71 : 7-40. Cowan, W. M., R. Guillery and T. P. S. Powell 1964 T h e origin of the mammillary peduncle and other hypothalamic connexions from the midbrain. J. Anat. (London), 98: 345-363. Crosby, E. C., T. Humphrey and E. W. Lauer 1962 Correlative Anatomy of t h e Nervous System. MacMillan Co., New York, 731 pp. Eccles, J . C., M. Ito and J . Szentagothai 1967 T h e Cerebellum a s a Neuronal Machine. Springer, New York. Glees, P., and R. A. Bailey 1951 Schichtung und Fasergrosse des tractus spino-thalamicus des Menschen. Mschr. Psychiat. Neurol., 122: 129141. Guillery, R. W. 1957 Degeneration in the hypothalamic connexions of the albino rat. J . Anat. (London), 91 : 91-115. Halpern, M. 1968 Effects of midbrain central gray matter lesions on escape-avoidance behavior in rats. Physiol. Behav., 3: 171-178. Hunsperger, R. W. 1956 Role of substantia grisea mesencephali in electrically-induced rage reactions. In: Progress in Neurology. J. Ariens Kappers, ed. Elsevier, New York, pp. 289-292. Hyndman, 0. R., a n d C. van Epps 1939 Possibility of differential section of the spinothalamic tract. A clinical and histological study. Arch. Surg., 38: 1036-1053. Jane, J . A,, J. P. Evans and L. E. Fisher 1964 An investigation concerning the restitution of motor function following injury to the spinal cord. J. Neurosurg., 21: 167-171. Johnson, F. H. 1954 Experimental study of spinoreticular connections in t h e cat. Anat. Rec., 118: 316 (abstract). Karplus, J. P., and A. Kreidl 1928 Gehirn und Sympathicus. VIII Mitteilung Pfluger’s Arch. Physiol., 219: 613-618. Kerr, F. W. L. 1974 The ascending tracts of the ventral funiculus of the spinal cord with special reference to a spinothalamic system. Anat. Rec., 178: 389 (abstract). Kerr, F. W. L., and H. H. Lippman 1973 Ascending degeneration following cordotomy and midline myelotomy in the primate. Anat. Rec., 175 : 356-357 (abstract). 1974 The primate spinothalamic tract a s demonstrated by anterolateral cordotomy and commissural mvelotomv. In: Advances in Neurology. J. J . Bonica, ed. -Raven Press, New York, 4 : 147-156. King, R. B. 1957 Postchordotomy studies of pain threshold. Neurology (Minn.), 7 : 610-669. Liebeskind, J. C., and D. J. Mayer 1971 Somatosensory evoked responses in the mesencephalic central gray matter of the rat. Brain Research, 27: 133-151. Liebman, J. M., D. J . Mayer and J. C. Liebeskind 1970 Mesencephalic central gray lesions and

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fear motivated behavior in rats. Brain Research, 23: . 353-370. - .- - . . Loewenfeld, I. E. 1958 Mechanisms of reflex dilatation of the pupil: historical review and experimental analysis. Documenta Ophthalmol., 12 : 185-448. Loewy, A. D., J . C. Araujo and F. W. L. Kerr 1973 Pupilodilator pathways in the brain stem of the cat: anatomical and electrophysiological identification of a central autonomic pathway. Brain Research, 60: 65-91. Magoun, H. W., D. Atlas, E. H. Ingersoll and S. W. Ranson 1936 Associated facial, vocal and respiratory components of emotional expression. An experimental study. J. Neurol. Psychopath., 17: 241-255. Mehler, W. R. 1957 T h e mammalian “pain tract” in phylogeny. Anat. Rec., 127: 332 (abstr ac t). Mehler, W. R. 1969 Some neurological species differences - a posteriori. New York Acad. Sci., 167: 424-468. Mehler, W. R., M. E. Feferman and W. J. H. Nauta 1960 Ascending axon degeneration following anterolateral cordotomy. An experimental study in the monkey. Brain, 83: 718-750. Mott, F. W. 1895 Experimental inquiry upon the afferent tracts of the central nervous system of the monkey. Brain, 18: 1-20. Nashold, B. S., W. P. Wilson and D. G. Slaughter 1969a Sensations evoked by stimulation in the midbrain of man. J. Neurosurg., 30: 14-24. 1969b Stereotaxic midbrain lesions for central dysesthesia and phantom pain. J . Neurosurg., 30: 116-126. Nauta, W. J. H. 1958 Hippocampal projections and related neural pathways to the midbrain in the cat. Brain, 81: 319-340. Nauta, W. J . H., and H. G. J. M. Kuypers 1958 Some ascending pathways in the brain stem reticular formation. In: Reticular Formation of the Brain. H. H. Jasper, ed. Little, Brown Company, Boston, pp. 3-30. Olds, M. E., and J. H. Frey 1971 Effects of hypothalamic lesions on escape behavior produced by midbrain electric stimulation. Am. J. Physiol., 221 : 8-18. Olszewski, J., and D. Baxter 1954 Cytoarchitecture of the h u m a n brain stem. Lippincott, 199 PP. Papo, I., and G. Caruselli 1970 T h e pain threshold after spinothalamic tractotomy. Neurochirurgie, 16: 513-524. Probst, M. 1902 Zur Kenntnis der Schleifenschicht und iiber centripetale Riickenmarksfasern zum Deiters’schen Kern, zum Sehhiigel und zur Substantia reticularis. Mschr. Psychiat. Neurol., 11 : 3-12. Rasmussen, A. T. 1932 The principal nervous pathways. Macmillan Company, New YorkLondon. Reynolds, D. V. 1969 Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science, 164: 4 4 4 4 4 5 . Rothman, M. 1903 Zur Anatomie und Physiologie des Vorderstranges. Neurol. Cnbl., 22: 744-746. Schiff, M. 1854 Sur l a transmission d e s impressions sensitives d a n s la moelle Cpiniere. C. R. Acad. Sci., 38: 926-930.

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Spiegel, E. A . , M. Kletzkin and E. G. Szekely 1954 Pain reactions upon stimulation of the tectum mesencephali. J. Neuropath. Exp. Neurol., 1 3 : 212-220. Stookey, B. 1943 The management of intractable pain by chordotomy. Res. Publ. Ass. nerv. ment. Dis., 23: 4 1 6 4 3 3 . Tanaka, T., H . Y u and S. T. Kitai 1971 Trigeminal and spinal inputs to the facial nucleus. Brain Research, 33: 504-508.

Walker, A. E. 1943 Central representation of pain. Res. Puhl. Ass. nerv. ment. Dis., 23. 63-85. White, J. C. 1963 Anterolateral cordotomy - its effectiveness in relieving pain of non-malignant disease. Neurochirurgia, 6 : 83-102. White, J. C., and W. H. Sweet 1969 Pain and the neurosurgeon. C. C Thomas, Springfield, Ill., 1000 pp. Willis, W. D., and R. G. Grossman 1973 Medical neurobiology. C. V. Moshy, St. Louis, 457 pp.

PLATE 1 E X P L A N A T I O N OF F I G U R E S

All figures are from the experiment with total transection of the ventral funiculus and all are stained by the Nauta Gygax method. 4

Fine terminal degeneration in the ipsilateral N. paragigantocellularis dorsalis. X 265.

5

Terminal degeneration in magnocellular division of ipsilateral medial geniculate body. X 500.

6

Degeneration i n the ipsilateral N. cuneiformis.

X

7

Subnucleus lateralis of periaqueductal gray.

500

X

500

VENTRAL SPINOTHALAMIC TRACT Frederick W. L. Kerr

PLATE 1

351

PLATE 2 E X P L A N A T I O N OF F I G U R E S

352

8

Terminal degeneration in the ipsilateral N . of Darkschewitz. X 500.

9

Degenerating fibers in N. of Edinger Westphal.

X

665

10

Dorsolateral aspect of rostra1 part of the red nucleus showing low density terminal degeneration. X 265.

11

Postero-medial hypothalamic area showing degenerating fibers running through it and some which appear to be terminating. X 500.

VENTRAL SPINOTHALAMIC TRACT Frederick W. L. Kerr

PLATE 2

353

EXPI.ANA1ION

354

OF F I G U R E S

12. 13

Terminal degeneration in the pars muliformis of t h e N. medialis dorsalis ipsilaterally (12) and contralaterally (13); this is representative of t h e relatively symmetrical bilateral projections of t h e V.S.T.T. to this area. X 265.

14, 15

“Bursts” of terminal degencxation in ipsilateral (14) and contralateral (15) N . ventralis posterolateralis. The degeneration in t h e Iattcr is considerably less pronounccd. X 265.

V E N T R A L SI’INOTIIALAM IC , T R A C T Frederick W I> Krrr

355