Pain, 14 (1982) 247-265

Elsevier Biomedical Press

247

Cortical Responses Evoked by Tooth Pulp Stimulation in the Cat. Surface and Intracortical Responses

A. Roos, B. Rydenhag and S.A. Anderson Department of Physiology, University of GBteborg, Box 33031, S-400 33 Giiteborg (Sweden)

(Received 8 December 1981, accepted 26 March 1982)

Summary

In lightly chloralose-anaesthetized cats selective stimulation of tooth pulp affer- ents elicited responses in coronal, anterior suprasylvian and adjacent cortical gyri. In

the lateral part of coronal gyrus the potentials evoked from the contralateral canine

tooth pulps were initially positive. Such responses from the upper and lower teeth had different cortical distribution suggesting a topographical organization. In the regions adjacent to those with initially positive responses stimulation of the same

tooth pulp evoked initially negative potentials. Stimulation of ipsilateral tooth pulp afferents elicited almost exclusively initially negative potentials with a similar distribution as the responses of contralateral teeth but with longer latency. Laminar

analysis showed that the region with initial positivity in the response to stimulation of the tooth pulp coincided with an intracortical negative focal potential of maxi- mum amplitude mainly in lamina IV. In areas with initially negative responses the maximum of the focal potential following tooth pulp stimulation was obtained in superficial cortical layers.

It is postulated that the projection system underlying the initially positive cortical

responses has a topographically arranged cortical projection terminating mainly in lamina IV. The projection system eliciting the initially negative potentials, has a

widespread cortical distribution and produces excitation predominantly in the superficial laminae.

Introduction

The afferent pathways mediating tactile sensibility and projecting to the cerebral cortex with short latency are characterized by a topographical pattern at all levels. Stimulation at a certain peripheral location elicits a positive-negative potential and

0304-3959/82/0000-0000/$02.75 0 1982 Elsevier Biomedical Press

activation of single cells in a limited cortical region. Lesions in this area produce

sensory deficits in a corresponding peripheral field. Conversely, electrical atimufa-

tion at that cortical site may evoke a sensation projected to the appropriate

peripheral part of the body. In the search for the central projection of pain many investigators have been looking for similar properties in the pain pathways hut with

little success,

Electrical stimulation of the somatose~so~ cortical areas may produce sensations of tingling, numbness or electricity but not pain 169,701. Limited cortical lesions give usually no deficits in the sensitivity to pain. On the other hand. chronic pain

conditions may be eliminated by a variety of subcortical lesions althougl~ the pain

often returns, usually after a few months. Experimental lesions in the parietal cortex of monkeys have suggested that the pain sense has an extensive cortical localization and only rather iarge cortical lesions seem to influence the perception of pain [68]. A change in the reactions to painful stimuli has also been observed after bilateral

cortical lesions in cats. Lesions in SII produced an increase of the pain threshold and the effect was more pronounced when also the cortex of surrounding sulci was

damaged. Ablation of only SI increased the latency but not the threshold of the response [ 1 I].

Another type of observation suggesting a cortical involvement in pain perception has been made in studies of the neuronal potentials evoked by noxious stimuli.

Activity in the tooth pulp afferents are presumed to produce pain as the major

sensation [80] and electrical stimulation of these afferents has been reported to give

cortical surface potentials as we11 as single unit activity in a localized region of the somatosensory cortex in rat [77], cat [9,85] and monkey [ 12,83,84]. The observations

made in these experiments are in conflict with the findings made in experiments with lesions [11,68] and cortical stimulation 169,801. Thus the localized potentials ob- served on tooth pulp stimulation appear to represent only a part of the cortical

region responsible for the appreciation of pain. There is evidence from studies in awake humans that pain may have a much more

widespread cortical effect than has been supposed after experiments in anaesthetized animals, i[n the awake man electrical stimulation of the tooth pulp induces a Iong latency widespread cortical response [X]. The amplitude of parts of this response has been suggested to correlate with the intensity of the perceived pain 1251. An

involvement of extensive regions of the cerebral cortex in the sensation of pain is also suggested by the large zones of increased blood flow following a painful

stimulus to the skin as compared to a localized increase of the blood flow in the postcentral gyrus after a tactile stimulus [54]. Whether the widespread cortical

activation seen after a painful stimulus is due to the sensation of pain or due to

arousal cannot be settled [ lS,lS]. The present study is the first in a series of investigations aimed to analyze in some

detail the neuronal activity induced in the cortex by noxious stimuli. This paper deals with the gross cortical potentials elicited by electrical stimulation of tooth pulp afferents in the lightly anaesthetized cat. Special attention is focussed on differences between activity evoked via the non-specific system compared to neuronal activity

with lemniscal properties.

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Methods

The experiments were performed on cats, anaesthetized with cx-chloralose, 60 mg/kg given iv. The upper and lower canine teeth on both sides were prepared for selective electrical stimulation of tooth pulp afferents. Small holes were drilled into the dentine on opposite surfaces of each tooth. Thin silver wires, insulated except at their tips, were inserted into the cavities and firmly fixed with dental amalgam. During this procedure the effectiveness of the electrical stimulation of the tooth pulp afferents was controlled by stimulation with single electrical pulses (0.5 msec duration) from a constant current pulse generator. The electrode position was considered adequate when a jaw opening reflex was elicited at a current strength less than 100 PA; usualty the threshold for producingjaw opening was about 20 PA. The teeth were then covered with dental cement to prevent short circuiting by saliva and spread of current to the gingiva. During the experiment the tooth pulps were stimulated with short trains consisting of 3-4 pulses at an interval of 1.25 msec and a pulse duration of 0.5 msec. Low threshold afferents in the infraorbital nerves were stimulated electrically via pairs of needle electrodes inserted into the upper lip bilaterally. In some experiments the infraorbital nerves were dissected for direct electrical stimulation. Electrical stimulation of afferents from the forelimbs was performed via bipolar electrodes inserted into the skin. Low threshold mechanore- ceptors were stimulated with a hairbrush or a jet of air operated via electromagnetic devices.

Craniectomy was performed and the coronal gyrus and the adjacent cortex were exposed and covered with warm mineral oil. To avoid pulsations during the microelectrode recordings a closed chamber [S] was fixed to the bone surrounding the trepanation. Unintentional nociceptive stimulation was minimized by treating the wound surfaces with a local anaesthetic (Xylocaingel @). The animals were immobilized with gallamine triethiodide and artificially respired with air. End tidal pC0, was continuously monitored during the experiment and kept at the same level as when the cat was breathing spontaneously, usually 4.555%. In some experiments a small cortical area was cooled by a metal probe with a contact surface of 20 mm2. The probe was perfused with alcohol at - 15°C. An Ag-AgCl electrode was mounted in the centre of the cooling surface which allowed recording of the activity of the cooled cortex. The effect of strychnine on the cortex was tested by application of a piece of filter paper (1 mm X 2 mm) soaked in 0.1% strychnine sulphate solution.

The cortical surface responses were recorded with ball-tipped Ag-AgCl electrodes. The potentials were amplified in a conventional amplifier and displayed on an oscilloscope. The responses to consecutive stimuli could be averaged on an HP 5480A averager. Usually 16 responses were averaged.

The following abbreviations are used: CUT, contralateral upper canine tooth; IUT, ipsilateral upper canine tooth; CLT, contralateral lower canine tooth; ILT, ipsi- lateral lower canine tooth; CIN, dissected contralateral infraorbital nerve; CL, contralateral upper lip; IL, ipsilateral upper lip; CFL, contralateral forelimb; IFL, ipsilateral forelimb.

Results

Surface potentials evoked by tooth pulp stimulatwn

To test if the method of tooth pulp stimulation used in the present series of experiments elicited cortical activity related only to excitation of tooth pulp afferents

the amplitude and latency of the cortical evoked responses were measured during

increasing strength of the electrical stimulation of CUT and the evoked potentials

were compared to the responses obtained by stimulation of low threshold facial

afferents (CIN). The evoked potentials were recorded at the cortical points of

maximum amplitude of the initial positivity produced by the respective stimuli. Graphs representing the relation between the amplitude of this potential and the

intensity of the stimulus to CUT and CIN are shown in Fig. I. Examples of the

cortical potentials are shown in the insets. The tooth pulp evoked responses were always of small amplitude compared to the responses evoked by stimulation of CIN.

At supramaximal stimulation strength the amplitude of CIN evoked responses was 7-8 times larger than that of responses obtained at stimulation of CUT. The threshold intensity to evoke a cortical response by CUT stimulation was 23 uA. With increasing stimulation strength the amplitude of the initial positivity increased

w YV

Input output relation

>”

500

450

400

350

300

!50

!OO

150

CO

50

Fig. 1. Peak amplitude of initially positive cortical surface potentials at increasing stimulation strength of

CUT (dashed line) and CIN (continuous line). Potentials l-IV and A-D are examples of averaged

responses obtained at different stimulation strengths of CUT and CIN respectively. Positivity downwards

in this and following figures. X-axis: stimulation strength. Left Y-axis: amplitude of CUT evoked

responses. Right Y-axis: amplitude of CIN evoked responses.

251

rapidly to reach a maximum at about 50 yA. A further increase of the stimulation

strength to 10 mA gave no additional increase of the amplitude neither did any potentials of shorter or longer latency appear. The latency of the response to CUT stimulation was about 10 msec at all stimulation strengths. Small changes of the latency were observed only at intensities close to the threshold value. At stimulation

of CIN the latency was about 4 msec and only 10 uA were required to elicit a threshold cortical response. The amplitude of the initially positive cortical response

increased until the stimulation intensity was about 80 p,A. These observations

indicate that the technique used for stimulation of the tooth pulp exclusively activates the tooth pulp afferents without activating low threshold peridental affer-

ents.

Distribution and configuration In the exposed cortical area large surface responses were evoked by stimulation of

cutaneous afferents. In particular positive-negative potentials of short latency were

evoked in the coronal gyrus on stimulation of low threshold afferents in the face. Within the same cortical area small responses were evoked also on stimulation of

tooth pulp afferents. In contrast to the results reported in some earlier investigations [9,12,83-851, stimulation of tooth pulp afferents elicited surface potentials also in areas outside the coronal gyrus including the anterior suprasylvian and the sigmoid gyri and responses were obtained from both contralateral and ipsilateral teeth.

In most experiments a systematical mapping with surface electrodes revealed responses with an initial positivity by stimulation of CUT and CLT (Figs. 2A and 3). These responses were found in a limited region of the coronal gyrus in front of and

slightly lateral to the anterior part of the suprasylvian sulcus. In some animals initially positive responses to stimulation of CUT and CLT were found in an area

lateral to the ansate sulcus and in the posterior part of anterior ectosylvian gyrus in

Fig. 2. Distribution and appearance of averaged cortical surface potentials evoked by stimulation of CUT (A) and IUT (B). Localization of investigated cortex shown as hatched in the inset. G.S.S.A: gyrus suprasylvius anterior; G.E.S.A: gyrus ectosylvius anterior; G.S: gyrus sigmoideus; G.C: gyrus coronarius.

/

Fig. 3. Distribution and appearance of averaged cortical surface potentials elicited by tooth pulp

stimulation. Upper trace in each pair: CUT: lower trace: CLT. Areas showing initially positive surface

potentials are encircled. upper region represents CUT and lower area CLT. Investigated cortex hatched in

the inset. Abbreviations as in Fig. 2.

area A of Carreras and Andersson [22]. The detailed characteristics of the tooth pulp

projection to these latter areas have not been investigated. Stimulation of the ipsiiateral teeth generally gave rise to negative surface potentials (Fig. 2B). In a few cases responses with a small initial positivity were found at stimulation of IUT or ILT. Such potentials were found within the same region of the coronal gyrus as that of the positive-negative potentials elicited from CUT and CLT respectiveiy.

The initially positive potentials elicited by stimulation of the contralateral canine teeth occurred exclusively within the cytoarchitectonic area 3b. Initially negative responses were found both in parts of, area 3b and in adjacent cytoarchitectonic areas. Stimulation of CUT and CLT (Fig. 3) elicited positive-negative potentials in two partially overlapping areas of the coronal gyrus. At some locations a small negativity representing the incoming volley preceded the initial positive deflection. The positive-negative potentials evoked from CLT were located more laterally in the

253

coronal gyrus compared to the response at stimulation of CUT. Stimulation of each

contralateral tooth gave potentials of maximum amplitude in a certain region. With increasing distance from this area the amplitude of the response decreased.

In large areas adjacent to those exhibiting initially positive responses stimulation

of contralateral teeth elicited negative or negative-positive potentials. There was no strict borderline between the areas giving initially negative and initially positive

responses and the size of the areas showing these types of responses varied slightly

between animals. In the border zone initially negative and initially positive responses could occur intermingled. It was also noted that in this zone the negative responses sometimes had a pronounced late positivity as illustrated in Fig. 2A in the records

obtained in the anterior parts of the coronal gyrus. The initially negative responses were rather similar in appearance, amplitude and distribution whether contralateral or ipsilateral afferents were stimulated (Fig. 2A, B) indicating that this potential had

no topographical pattern. The negative potentials were often of long duration and showed usually two

successive components. These waves were most pronounced in responses to stimula-

tion of the ipsilateral teeth but were seen also in contralateral responses without an

initial positivity. Only one negativity occurred, however, if the tooth pulp stimula- tion elicited a pronounced initial positivity.

negation to responses from cutaneo~ affereents

Stimulation of face and forelimbs elicited surface potentials of short latency within the investigated area, indicating that this part of the cortex received input also from low threshold cutaneous afferents. Fig. 4 illustrates surface potentials evoked at 5 different cortical locations. Responses were evoked by stimulation of CUT, IUT, CL, IL, CFL and IFL. The records are taken from the same experiment as that illustrated in Fig. 2. The positive-negative potentials evoked from the contralateral tooth pulp afferents are closely related to locations with potentials of similar

CUT

lb %A

IUT CL IFL

Fig. 4. Appearance of averaged cortical surface responses elicited by stimulation as indicated at locations as shown in the inset. Amplification bars for CUT and IUT and for CL to IFL respectively. Abbrevia- tions as in Fig. 2.

appearance but with much larger amplitude evoked by stimulation of low threshold afferents in the contralateral lip. Such a relation did not exist with regard to the initially negative potentials which were found also in areas with large initial

positivities from the contralateral forelimb and face (Fig. 4, location V). Fig. 4 also illustrates that there was a striking similarity between the initially negative responses

whether they were elicited by any contralateral or ipsilateral stimulation. lpsilateral

stimulation evoked a response with two negative components at most locations

where the contralateral stimulation produced an initial positivity except at the area of maximal amplitude of the contralateral response. At such a location (fV in Fig. 4)

the ipsilateral response was often small. in the response to stimulation of the afferents from the lips similar negativities with two successive waves were obtained

provided that the current applied via the intracutaneous stimulating needles was

sufficiently strong ( b 5 mA) and the responses did not exhibit a large initial positivity. In the areas of specific projection the response was positive-negative

without a second negative component. Conseyucntly this type of negative response was found in a more extensive area when ipsilateral afferents were stimulated.

Latencies

The appearance of the initially positive potentials at each recording site was rather constant on consecutive stimulations of contralateral teeth and the onset

latency varied less than 2 msec. In a recording site within the region of initially

positive responses, the range of onset latencies was 8.5512.5 msec with a mean of 9.8 msec. Within this area there was no location with the shortest latency but rather the

short and long latency responses were intermingled throughout the region. In the few experiments where ipsilateral tooth p&p stimulation elicited initially positive re-

sponses, these potentials showed similar latency as the contralateral responses but the ipsilateral evoked potentials were less constant in amplitude and latency on successive stimulations.

The initially negative potentials on stimulation of contralateral teeth were more variable both in onset latency and amplitude. On consecutive stimulations the tatency range was 9--20 msec. Due to this insecure activation there were difficulties to measure latency on single responses and ail latency measurements of these potentials were made on averaged recordings. Mean onset latency of the initially

negative average responses was 10.0 msec. The latency and amplitude differences of the ipsilateral evoked responses were

even more pronounced than in the contralateral response. In the averaged potential the mean onset latency was 14.0 msec indicating that the cortical activation from the

ipsitateral teeth was about 4 msec delayed compared with the contralateral re-

sponses.

Intrucorticul focal potentials

The regional difference in the appearance of the evoked response on tooth pulp stilnulation was further elucidated by recordings of the field potentials at different depths below the cortical surface during peripheral stimulation. There were consider- able variations in the polarity and amplitude of the field potentials evoked by

255

A

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‘... ! “” 1.0 ‘;-‘\; :

4 :: 2.0

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0 = CL

A=CUT

C - A.

D ,’

P’ ,.I’ CT “,’ 1.0

6. I.

. . . .

-2.0

250 &

Fig. 5. Amplitude and polarity of intracortical responses evoked by stimulation of the contralateral upper

tooth pulp and contralateral upper lip respectively at different depths. Recording locations as indicated in

the inset.

A F d

I I c :I;

BJ+ D ;:

4 L--- l i d_r 125vV

25 msec Fig. 6. Focal potentials and nerve cell action potentials recorded with microelectrode in cortical lamina IV. Responses were evoked by electrical stimulation of: A: CUT, B: IUT, C: CL and D: IL.

30

stimulation of tooth pulp afferents in neighhauring penetrations. Some systematic regional differences were, however, observed. Thus, in the lateral region of the coronal gyrus where stimulation of contralateral teeth evoked an initially positive surface response the intracortical potential became negative below the surface and attained its maximal amplitude deep in the cortex (below I mm: Fig. SC). Outside

this region in areas with initially negative surface responses at tooth pulp stirn~ll~~tion the intracortical responses were negative throughout the cortex hut had their maximal amplitude more superficially (Fig. SA). The depth profile of the intracorti-

cal potential was rather similar at stimulation of (‘1. and CUT at locations where the surface responses were similar. If stimulation of the tooth pulp elicited a surface

negativity and the afferents from the lip gave an initially positive potential, stimula-

tion at CL produced a maximal negativity deeper in the cortex than the CUT

response (Fig. 5B). In the intracortical recordings stimulatioil of the teeth frequently elicited complex

and long lasting focal potentials with superimposed spikes. Fig. 6 shows examples of potentials recorded in the coronal gyrus at a depth of 1 mm in a penetration in the transitional region between initially positive and initially negative surface responses

evoked by stimulation of the contralateral canine teeth. Stimulation of CUT (A) evoked a relatively short latency, steeply rising focal potential with superimposed spikes which were followed by a second peak also with spikes. Stimulation of the IUT (B) evoked a slowly increasing potential with longer latency. The peak ampli- tude of the ipsilateral response had a similar latency as had the second peak in the contralateral response. Stimulation of contralateral or ipsilateral low threshold afferents in the face, C and D respectively, produced responses with much shorter latency and with only one peak. The time course of the two components in the

intracortical response was closely related to the presence of two negative waves in

the surface response (cf. Figs. 2 and 4).

The simultaneous existence of responses with different appearance after tooth pulp stimulation raised the question whether they were elicited by the same or different thalamo-cortical projection systems. In 5 experiments the cortical responses were studied during local cooling of the region with initially positive responses or

during application of 0.1% strychnine sulphate solution locally on the eortex exhibiting initially positive or initially negative responses.

Fig. 7A shows averaged recordings of potentiais evoked at locations I and I1 as indicated in the schematic drawing of the cortex. The cortex was cooled via a probe with a contact surface as indicated and applied on the region with initially positive response. During the cooling of the probe with - 15°C alcohol the responses to stimulation of CUT were recorded. In the cooled cortex the potentials could be recorded via an electrode mounted in the surface of the probe (location I). Shortly after starting of the cooling the response in the cortex underlying the probe began to decrease. The initially negative response evoked in cortex outside the region showing initially positive potentials did not change during the cooling. At rewarming of the cortex there was a period with a strong augmentation of the initially positive

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0 1% StQdxm

?\,’ /I------ “r‘\--_-- Fig. 7. Effects of cooling (A) and strychnine application (B) on initially positive (AI and BI) and initially negative (Al1 and BII) averaged cortical surface responses. Abbreviations as in Fig. 2.

response. This effect was only local and there was no influence on the initially negative responses outside the cooled region.

To obtain further evidence of separate mechanisms underlying these two types of potential a strychnine sulphate solution was applied locally via a small piece (2 mm2) of filter paper to the cortex during the recording of the responses evoked from the tooth pulp.

Fig. 7B illustrates an experiment where strychnine was applied to the cortical area giving initially positive responses at stimulation of CUT. Shortly after application of strychnine both the positive and the negative component of the response were strongly augmented. At locations with initially negative responses the amplitude and latency remained unchanged during the period of strychnine action. Application of strychnine at sites with initially negative potentials did not markedly change the appearance of the negative response nor did the initially positive response to tooth pulp stimulation increase in the appropriate area. At locations with initially negative response to tooth pulp stimulation an initially positive potential elicited by stimula-

tion of low threshold afferents in the contralateral face or forelimb at the area of

strychnine application was strongly augmented. This observation and the presence ttl strvchnine spikes indicate that the drug exerted :I proper action,

Discussim

In a study of the central effects of activity in tooth pulp afferents it is essential that the stimulation does not activate low threshold periodontal receptors or

afferents. In some earlier studies a spread of current to include such afferents has given erroneous results [vide X2]. The constant latency and configuration of the responses indicate activation of tooth pulp afferents exclusively. The tooth puip afferent nerve seems to contain not only A6 but also C fibres [5.6] but a late col~ponent due to C fibres was not disclosed in the cortical response.

In previous studies a cortical projection from the tooth pulp has been found in

the somatosensory area corresponding to the topographical projection from the jaws [9.12,55,82-853. Initially negative potentials of small amplitude have been obtained

when tooth pulp afferents were stimulated in cat. The present results have confirmed a projection of the tooth pulp afferents to parts of the coronal gyrus as previously

reported. In addition tooth pulp evoked potentials were found in a large cortical region including the entire coronal and adjacent gyri. This finding is in contrast to the earlier studies [9,12,83-851 but is in conformity with findings of evoked cortical

potentials on tooth pulp stimulation in awake humans 1261 and suggests that the restricted area of cortical responses observed previously on tooth pulp stimulation in animals may be an effect of anaesthesia. An increased blood flow in large cortical areas indicating increased neuronal activity has been reported on noxious stimula- tion of the skin in awake humans [54]. It is tempting to suggest that any painful stimulus excites cells in a wide cortical region. It is not possible, however, to

conclude whether this activity is concerned with the sensation of pain or reflects increased cortical activation due to arousal but these phenomena may have neuronal

circuits in common [ 15.18,78].

The appearance of the cortical potentials evoked from the teeth differed from those of previous studies in cat. In contrast to the initially negative responses usually

found in the area with topographical projection from the face 1851 many of the experiments of our investigation showed initially positive responses in this region. Thus, tooth pulp stimulation elicited a response similar to that evoked by stimula- tion of low threshold afferents contralaterally in the face. The wave form was simitar but the latency was 2-3 times longer and the amplitude much smaller when the

response was elicited from the tooth. The initially positive response did not appear in all experiments. This type of

potential was the first to decrease in amplitude and could eventually disappear during the course of an experiment. It appears therefore to be rather sensitive to the condition of the animal. It is at present not possible to conclude if this fragility is due to peripheral factors such as injury or blockade of certain types of nerve fibres in the tooth pulp or to decreased efficiency in synaptic activation at central levels.

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We consider, however, the lack of initially positive responses in some experiments as due to technical difficulties rather than to functional differences.

The initially positive surface responses evoked by tooth pulp stimulation were found in the cytoarchitectonic area 3b of the coronal gyrus according to Hassler and Muhs-Clement [35], thus in a region where low threshold cutaneous afferents from perioral regions and whiskers project [32,53]. Both the upper and lower canine teeth evoked initially positive surface potentials in this region. Although the projection areas were slightly overlapping, a constant finding was that the mandibular teeth evoked a maximum response more laterally in the region of 3b. It is also known from studies of the projection from low threshold cutaneous afferents that the inferior alveolar nerve and the mental nerve evoke maximum responses more laterally than the maxillary nerve in this region 1531. Intracortical recordings in those areas showed cellular discharges and focal potentials of short latency and maximal amplitude in deep cortical layers. Thalamo-cortical fibres arising in VPL and VPM have a topographically arranged termination in the cortical laminae IIIb and IV of the somatosensory cortex of both cat [SO] and monkey [46]. This type of projection is considered to constitute the specific thalamo-cortical connexions. Stimulation within the appropriate thalamic nuclei gives rise to a characteristic positive-negative ‘aug- menting’ cortical response. We suggest that the positive-negative response elicited from the tooth pulp is mediated via a similar thalam~cortica1 projection system as that giving the initially positive responses from low threshold receptors via the specific nuclei, therefore the underlying thalamo-cortical projection will be denoted the specific tooth putp projection.

It has previously been suggested that the tooth pulp afferents primarily mediate the sensation of pain [19,80] and in humans electrical stimulation of the tooth pulp at intensities used in the present experiments is perceived as pain [59]. Electrical stimulation of the tooth pulp in unanaesthetized cats produces nocifensive reactions; these behavioural reactions increase when the stimulation is given as short trains of pulses [86]. This correlates well with our results showing an increased amplitude of the cortical response to tooth pulp stimulation when a short train of pulses was used instead of a single pulse. It has been reported that weak electrical stimulation of teeth can evoke non-painful sensations 158,591, sometimes referred to as pre-pain [65,663. Such sensations are often described as throbbing or pricking and are unpleasant although not really painful [58]. It is not settled if this type of sensation is produced by the artificial electrical activation of a few tooth pulp afferent fibres or if it represents other modalities such as touch or temperature. In the latter case the specific cortical response could represent the projection of non-pain fibres with a similar afferent path as from low threshold peridental receptors. Since the dominat- ing sensation from tooth pulp afferents is pain it appears most likely that the positive-negative potentials represent a specific component in the neuronal mecha- nism underlying pain rather than an input from low threshold tooth pulp receptors. A specific component in the pain projection system may be important in the perception and mediate specific characteristics such as localization and quality typical of the epicritic sensibility [36].

It may be argued that the initially positive response is the primary one and that

261)

the initiahy negative potentials are secondary, due either to eIectrotonic spread of current or to synaptically activated intracortical connexions. The depth profiles make an electrotonic spread from subcortical structures unlikely and the results suggest that a more likely explanation is that the initially positive and the initially negative responses are due to different thalamo-cortical projection systems. The initially negative responses have simitar distribution and wave form whether elicited

by stimulation of ipsiiateral or contralateral teeth, which suggests that they are induced via a final common path. i.e., a thalamo-cortical system which has a bilateral input. The shorter latency of the contralateral cortical response may reflect

latency differences which are found already at the thalamic level [40,8X]. The

findings in the cooling experiments suggest that there was no direct relation between responses with an initial positive potential and the initially negative responses

obtained in other cortical areas. The different action of strychnine on the initially

positive and the initially negative potentials also suggests that the underlying

synaptic activation is different. It has been assumed that strychnine facilitates the responses due to removal of inhibition [7]. The present findings therefore suggest

that the initially negative responses are due to excitation rather than to a sequence of excitation and inhibition which may occur in cellular potentials in the area of initial positivities.

The existence of thalamo-cortical connexions, different from the specific ones, was suggested long ago by Morison and Dempsey [63] who concluded that *there exist between thalamus and cortex at least two systems with very different physio- logical properties.’ They considered the other system, which usually is referred to as

‘ the unspecific tha~amo-cortical projection,’ to have a diffuse cortical termination.

According to the theory advanced by Morison and Dempsey [30,64] the main function of such an unspecific system was to regulate the rhythmic activity in

thalamus and cortex. It was supposed to originate in the intralaminar nuclei

[41-43,451. Activity in this system gave rise to the initially negative waxing and

waning recruiting cortical response. There are now indications that the intralaminar nuclei are of importance in the

perception of pain. Lesions of the medial and intralaminar nuclei in cats profoundly

reduce or eliminate escape behaviour to tooth pulp stimulation or electric grid shock [5 1,611. Similar lesions in man have been reported to relieve intractable pain temporarily [57,87] although the somatosensory discriminative capacity is preserved. It was suggested that the cortex was influenced via a series of intrathalamic connexions [41]. A direct projection exists, however, from some intralaminar nuciei to superficial layers in a wide cortical area. Thus, there is evidence of connexions

from centralis lateralis (Cl) to cortex [49,52], and a certain degree of topography seems to exist in this projection with a relation between the motor cortex and the anterior parts of Cl and between the sensory cortex and the posterior parts of Cl [39,81]. Cells in Cl and in the anterior part of centrum medianum (CM)-parafascicu- far (pf) complex can be antidromically discharged from the sensorimotor cortical

areas [2]. There is also morphological evidence of a scanty projection from CM-Pf to the sensory and motor areas [ 16,29,49]. Spinothalamic fibres terminate in these thalamic nuclei [ 13- 15,47,60] which contain a number of cells responding to noxious

261

stimuli [1,23,24,31,71]. Thus, anatomical evidence suggests that not only a mukisyn- aptic but also a direct cortical projection from medial thalamic nuclei could give rise to the recruiting response as well as to the widespread initially negative potentials at noxious stimulation [ 151.

The posterior group (PO) of thalamic nuclei have been suggested to relay noxious input to the cerebral cortex [72]. Anatomically [20,34,37,48,62,67] there are connex- ions from PO to the posterior part of the anterior ectosylvian gyrus (area A and part

of area B) [22] where cells can be driven by noxious stimuli. There seems, however, not to be evidence of a projection from PO nuclei to the area investigated in this

study. At least part of the nociceptive information may be mediated to the cortex via

intrathala~c connexions to the ventrobasal complex [79]. Such a possibility is

supported by the finding that electrical stimulation medially in thalamus influences

cells in the specific nuclei [56,75,76]. Recent evidence from studies of the nociceptive input to VPL and VPM suggests that these nuclei may have more complex

connexions than has been assumed [ 171. The earlier studies indicated that the VB

neurones only have ‘lemniscal’ properties responding only to innoxious stimuli [73].

There have, however, also been findings of cells in VPL and VPM with bilateral wide

receptive fields and convergence of different modalities including responses to

noxious mechanical stimuli or stimulation of AS and C fibres [10,17,33,40,88]. A number of cells responding to thermal or to strong mechanical stimulation but not

to light touch have also been found in VPM [74] and VPL [21,38]. Thus the ‘dendritic’ character of the recruiting response with a long time constant and associated with superficial excitatory synaptic potentials rather than discharges of action potentials [27,28,44] may partly be generated via projections arising in the specific thalamic nuclei. It should also be noted that the cortical projection from

these nuclei participate both in the transmission of information from peripheral recordings and in the generation of rhythmic activity [3,4].

The significance of the cortical responses with regard to the sensation of pain is a matter of speculation. The wide and bilateral distribution as well as other characters

of the initially negative responses suggest that it is caused by unspecific projection system leading to depolarization of many cells. The increased excitability may result

in discharges of cells in large parts of the cortex. Hypothetically this effect could be

counteracted by the inhibitory action of the specific projection system from both low and high threshold afferents. Pain may occur when the inhibition is overruled by

excitation. This hypothesis will be subject to analysis in forthcoming papers on the cellular activity following tooth pulp stimulation.

Acknowledgements

This work was supported by the Swedish Medical Research Council (Project No. 55) Magnus Bergvalis Stiftelse and The Medical Faculty, University of Goteborg.

Excellent technical assistance was given by Miss Ewa Lignell and Mrs. Kerstin OIson.

262

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