Functional properties of spinomesencephalic tract (SMT) cells in the upper cervical spinal cord of the cat

Puin, 45 (1991) 187-196 ?_ 1991 Elsevier Science Publishers A DONIS

P4IN

187 B.V. 0304-3959/91/$03.50

030439599100124B

01775

Functional properties of spinomesencephalic tract (SMT) cells in the upper cervical spinal cord of the cat Robert

P. Yezierski

Deparlmenr of Neurological Surgev, (Received

and James

G. Broton

University of Miami, Miami, FL 33136 (U.S.A.)

16 July 1990. revision received and accepted

11 October

1990)

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Response and receptive field properties were evaluated for 62 spinomesencephalic tract cells in the upper cervical spinal cord (ClLC3) of cats anesthetized with sodium pentobarbital and alpha-chloralose. Recordings w,ere made from cells in laminae I-VIII and X contralateral to antidrornic stimulating electrodes positioned in the rostral, caudal and intercollicular region of the midbrain. The mean antidromic threshold for all cells was 185 f 132 PA, and conduction velocities ranged from 2.3 to 38.6 m/set. Twelve cells were backfired from both midbrain and diencephalic stimulation sites. Receptive fields ranged from simple, i.e., ipsilateral forelimb or face, to complex, i.e., excitatory and/or inhibitory responses from large portions of the body. Peripheral receptive fields included muscles, joints, cornea, dura, forelimbs, hind limbs, tail, and/or testicles. Five functional classes of cells were observed: (a) wide dynamic range (14 cells); (b) high threshold (2 cells); (c) low threshold (4 cells); (d) deep/tap (11 cells); and (e) non-responsive (31 cells). Eight cells were evaluated for responses to different doses (5-150 pg) of intravenous (i.v.) serotonin. Two of the 8 cells exhibited excitatory effects, whereas 2 cells classified as deep/tap and 4 cells classified as non-responsive were not affected. The results of this study have shown the upper cervical component of the spinomesencephalic tract is made up of a heterogenous population of cells involved in the integration of varied inputs from large portions of the body. It is proposed that the large population of SMT cells in the upper cervical spinal cord may be involved in pain mechanisms, especially those related to the affective consequences of acute and chronic pain. Key words: Nociception;

Muscle;

Viscera;

Trigeminal;

Introduction A large proportion of neurons belonging to the spinothalamic [5.11,21,23,35], spinohypothalamic [lo], and spinoreticular [12,39,51,53] tracts are located in the upper cervical spinal cord. Sensory inputs to neurons in this region of the cord have been described for cells projecting to the ipsi- or contralateral thalamus [11,28,68]. In these studies spinothalamic tract (SIT) cells were found to have varying receptive field (RF) organizations including complex excitatory and inhibitory components involving forelimbs, hind limbs and/or oral-facial structures [11,28,68]. Responses to noxious mechanical and thermal, and non-noxious mechanical

-Correspondence to: Dr. Robert P. Yezierski, Department of Neurological Surgery, University of Miami, 1600 N.W. 10th Avenue. R-48, Miami, FL 33136, U.S.A.

Serotonin

stimuli, applied to cutaneous or deep (joint and muscle) portions of RFs, have also been described [11,28,68]. Recent studies in our laboratory have shown that spinomesencephalic tract (SMT) cells in the lumbosacral cord respond to inputs from cutaneous or deep structures, including joints, muscles, and viscera [77,82,83]. Furthermore, 38% of these cells have complex excitatory and inhibitory RFs [82] similar in many respects to those described for cervical and lumbar SIT cells [11,22,28,68], and cells projecting to the brain-stem reticular formation [16,46,51]. Recent anatomical studies have also shown that SMT cells have a differential segmental distribution, with 30% of the total population located in cervical segments Cl-C4 [81]. Although the functional properties of cells in the upper cervical cord challenge the accepted dermatomal organization associated with these spinal segments [26], the large number of projection neurons [5,10,11,21,23, 35,39,53,81] and the proposed propriospinal functions

IXX

of this cord level [58] also underscore the importance of additional studies directed at this region. Considering the large number of SMT neurons in the upper cervical cord [52.74,75.81], the present study was undertaken to assehs the range of stimulus conditions affecting cells projecting to different midbrain regions. Responses to noxious mechanical, thermal and chemical, non-noxious mechanical, and deep stimuli were evaluated. Preliminary results of this study have been reported [79].

Methods

Experiments were carried out in 9 adult male cats (3.5 4.5 kg). The set-up and protocol for preparing animals for each experiment have been described previously [77,82]. Briefly, animals were initially tranquilized with ketamine hydrochloride (Ketaset; 35 mg/kg. i.m.). the cephalic vein cannulated, and anesthesia induced with alpha-chloralose (60 mg/kg, i.v.). A tracheotomy was performed and animals artificially ventilated during immobilization with gallamine triethiodide (Flaxedil). Rectal temperature and end-tidal CO, were maintained within physiological limits, 36.5-37.5”C and 3.5-4.5%. respectively. Anesthetic level was maintained throughout experiments with an infusion of sodium pentobarbital (2.-4 mg/kg/h). Surgery included a dorsal laminectomy from the foramen magnum to the third cervical vertebrae, craniotomy, and a bilateral pneumothorax. Recordings were made from upper cervical SMT (SMT-UC) cells, segments ClLC3, backfired from a transverse array of 3 stainless steel electrodes (Rhodes; monopolar. 0.25 mm diameter) positioned at different rostrocaudal levels of the midbrain (0.5, 1.5. 2.5 mm from midline). For each cell efforts were made to obtain the lowest antidromic threshold. This was done to ensure antidromic activation of SMT axons and not axons coursing through the lateral midbrain to more rostra1 structures [77,82]. A second array of 3 electrodes was positioned across the mesodiencephalic junction to test for collateral projections of SMT-UC axons. Search stimulus parameters used to backfire cells consisted of 100 psec pulses (10 Hz) delivered at stimulus intensities between 200 IJ.A and 600 PA. Criteria for antidromicity included constant latency, frequency following at 333 Hz, and collision of orthodromic with antidromic spikes during a critical interval [77,82]. Based on waveform configuration of antidromic spikes, somatodendritic recordings were made from all neurons studied [62]. The primary objective of the present study was to evaluate the responses of SMT-UC cells to cutaneous (mechanical and thermal), deep (joint and muscle), and genital (testicle) stimulation as described in previous reports [77,82,83]. For each cell evaluation of muscle input was carried out by direct stimulation of exposed muscles (temporalis and trapezius) or by squeezing the

biceps or hamstring. A careful examination of the sktn overlying these latter two muscles W;I~ also done II~ order to evaluate the presence of both cutaneous and deep input to each cell. Similarly. &in o\Wl~ing Joint> was systematically examined using mechanical stimuli prior to joint movement. Inputs from muscle affercnt~ were also evaluated by the injection of hypertonic MIIIIC (1 ml) directly into exposed muscles (trapeziuh and temporalis). Inputs from oral-facial structures including the tongue, soft palate. and cornea were alho tested. A cotton-tipped applicator was used to stimulate the cornea and oral mucosa. A similar technique M;I> uaetl to stimulate the dura and superior sapittal sinus. Prior to dural stimulation a loop of suture wa:, used 10 cIc\atc the dura off the surface of the brain. ‘I his wa4 done IO a\,oid stimulation of cortical blood beasels. Serrated forceps. arterial clips (large and small) were used 10 deliver mechanical stimuli to the skin, tongue and testicles. Thermal stimuli were delivered with a Peltiertype stimulator (TDI). Eight cells were tested for responses to varying dose> of intravenous 5-hydroxytryptamine (5-HT) creatine phosphate (2.5-150 I-18 in isotonic saline). In all exprriments serotonin was injected into the right hind pau (cephalic vein). contralateral to recording sites in the spinal cord. Varying volumes of test solution. followed by a saline wash. were required to administer each dose of drug. The total volume of test solution plus wash was constant for each dose of drug administered. Rehponhe profiles to different stimulus conditions were stored on a laboratory computer (Medical Systems) for later analysib. At the conclusion of each experiment, lea~r~nh were made at midbrain stimulation and spinal recording sites and animals perfused with normal saline followed hy a 1VPsolution of potassium ferrocyanidr in 107 formalin. Brains and spinal cord5 were cut at 50 ptn on ;L frecr.inp microtome and counterstained with Neutral Red or (‘resyl Violet. Midbrain stimulation site.\ were identified by the Prussian-blue reaction and reconstructed with the aid of an overhead projector. Nuclear boundaries were determined based on criteria described by Berman [Xl. A similar procedure was used to reconstruct eiectro]ytic lesions (Fig. 1) marking the locations c>f carbon filament recording electrode:, [77]. Mean valuea for recording depths, antidromic thresholds and latencies are presented with standard deviations ( + S.D.).

Results

Sixty-two cervical SMT cells were recorded 523 4500 pm (mean 2224 f 965 pm) below the surface of the cord lo-- 15 mm caudal to obex. All 3 antidromic critena were met for 31/62 cells. Collision could not be demonstrated for 31 cells unresponsive to peripheral stimuli.

Fig. 1. Distribution of recording sites for 55 SMT cells recorded in spinal segments Cl (top row) and CZ-3 (bottom row). All recordings were made contralateral to midbrain stimulation sites. The locations of recording sites are plotted on both sides of the spinal cord to show the distribution of cells with different functional properties (see text). Line drawings were made from sections stained with cresyl violet (inset). Recordings were made at sites marked by electrolytic lesions (arrows, inset). Abbreviations: wide dynamic range (W): high threshold (H): low threshold (L): deep/tap (D): non-responsive (N). Calibration bar in inset equals 300 pm.

The distribution of recording sites for cells in segments Cl and C2-3 are shown in Fig. 1; all recordings were made on the left side of the spinal cord, contralateral to midbrain stimulation sites. Cells were recorded in laminae I-VIII and X, and 4 recording sites were located in or near the lateral cervical nucleus. Antidromic thresholds ranged from 20 to 600 PA (mean 185 1- 132 PA). The distribution of stimulation sites in the rostral, caudal, and intercollicular region of the midbrain included the periaqueductal gray (20 sites), deep layers of the superior colliculus (5 sites), and the mesencephalic reticular formation (30 sites; Fig. 2). This distribution coincided with the primary targets of cervical and lumbar projections to midbrain [74-761. A preferential distribution of antidromic sites associated with cells belonging to different functional classes was not observed (Fig. 2). Latencies of antidromic activation ranged from 0.7 to 12.0 msec (mean 2.6 * 2.0 msec). Given an average conduction distance of 27 mm from midbrain to the upper cervical cord, conduction velocities (CV) ranged from 2.3 to 38.6 m/set. Twelve cells were backfired from both midbrain and diencephalic sites with a mean antidromic threshold (rostra1 array) of 434 + 315 PA. Rostra1 stimulation sites included the central tegmental field, posterior nuclear complex, and central medial and parafascicular nuclei. The mean antidromic latencies for the 12 cells backfired from both

midbrain and thalamus were 1.8 + 0.4 msec and 1.7 + 0.7 msec, respectively. The mean CVs for cells activated from these locations were 15.0 m/set (midbrain) and 20.6 m/set (thalamus). The receptive field organizations of SMT-UC cells were characterized by responses to varied stimuli delivered to different parts of the body. Receptive fields were found to range from simple, i.e., excitation from the ipsilateral forelimb or face, to complex, i.e., excitatory and/or inhibitory effects from large portions of the body. The receptive field locations for 28 SMT-UC cells are illustrated in Fig. 3. Sixteen cells had simple RFs, whereas discontinuous or complex fields were found for 7 cells. 8 cells had RFs encompassing two or more divisions of the trigeminal nerve; four of these were bilateral. Inhibitory RFs were observed for 3 cells. A comparison between RFs for cells backfired from midbrain versus midbrain and thalamus was not possible due to the small number of cells receiving cutaneous or deep input in the latter population. In an effort to evaluate the range of receptive field sizes for SMT-UC cells, the entire body was tested with mechanical stimuli for each SMT-UC cell studied. Peripheral stimulation sites producing responses in SMTUC cells included muscles (temporalis, trapezius, biceps, hamstring), cornea. dura, joint, forelimbs, hind limbs, tail and/or testicles. Using criteria described

190

previously [82], 5 functional classes of cells were encountered: (1) cells responding best to noxious mechanical stimuli, but also to innocuous stimuli, i.e., wide dynamic range, accounted for 22% (14 cells) of the cells: (2) cells responding exclusively to innocuous (low threshold) stimuli represented 7% (4 cells); (3) noxious stimuli (high threshold) 3% (2 cells); (4) 18%’ (11 cells) responded exclusively to deep inputs (muscle, joint) or

A 2.5

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Fig. 2. Distribution of stimulation sites used to antidromically activate cells in the upper cervical cord. The functional class of each cell backfired from sites of lowest antidromic threshold in the caudal (P0.9) to rostra1 (A3.3) midbrain is indicated by W (wide dynamic range). H (high threshold), L (low threshold), D (deep/tap), or N (non-responsive). Abbreviations: MG, medial geniculate; SC, superior colliculus; BIN, brachium inferior colliculus; P, periaqueductal gray; IC. inferior colliculus; FTC, central tegmental field; A, cerebral aqueduct; 3. oculomotor nucleus: 4. trochlear nucleus.

tap stimuli (3 cells responded to noxious squeering of the testicles): and (5) 31 cells (50%) were unresponsive to any form of peripheral stimuli, e.g.. cutaneous 01 deep. An example of responses indicative of a SMT-1i<’ cell with a complex RF is shown in Fig. 4. This cell WH backfired from the intercollicular region of the midbrain at a stimulus intensity of 260 PA (1.9 mscc latency); the recording site was located in lamina V. Varying intensities of mechanical stimuli (PRESS.. PINCH and SQUEEZE) applied to the ipsilateral forepaw and hind paw produced graded responses to increasing stimulus intensities. The response to oscillating movements of a camel hair brush across the hairy skin (BRLJSH) was greater than that produced by ;t large arterial clip (PRESS.) applied to glabrous skin (Fig. 4A. C). Noxious thermal stimuli (55°C’: 30 set duration) evoked responses from both forepaw and hind pau (Fig. 4B, D). The thermal threshold for responses to hoth forepaw and hind paw stimulation was 50°C. In addition to cutaneous stimuli, SMT-UC cells were also tested for responses to chemical stimuli and stimulation of deep tissues. Examples of responses to these stimuli for two SMT-UC cells are shown in Fig. 5. Both of these cells were of particular interest as they illustrate input to SMT cells not previously reported. First, eucitatory-inhibitory input from different muscles ix shown in Fig. 5A-C. This cell was backfired from the periayueductal gray at a stimulus intensity of 1X0 PA (2.2 msec latency). The recording site was located in lamina VII. Excitatory responses were produced hy squeezing the exposed ipsilateral trapezius muscle (Fig. 5A, C); injections of hypertonic saline directly into the muscle (1 ml) produced a similar response (Fig. 5B). Inhibitory components of the cell’s RF were found when mechanically stimulating the dura around the superior sagittal sinus (Fig. 5A) or when squeezing the exposed temporalis muscle (Fig. 5C). The second response illustrated in Fig. 5 shows the excitatory effects of i.v. 5-HT on an SMT-UC cell recorded from the marginal zone of the first cervical segment. The antidromic stimulation site was located in the periaqueductal gray at the intercollicular level of the midbrain. The antidromic threshold was 100 PA (1.5 msec latency). The cell’s cutaneous RF was restricted to the middle toes on the ipsilateral forepaw. Responses were obtained to both non-noxious (BRUSH) and noxious (SQUEEZE) stimuli (Fig. 5D); no detectable input was obtained from deep structures, i.e., muscle or joints. In addition to mechanical stimuli, the effects of 7 doses of i.v. 5-HT (2.5-150 pg) were also evaluated against the cell’s spontaneous discharge. The responses in Fig. 5E and F show the excitatory effects of 30 pg and 100 pg of i.v. 5-HT. Following 30 pg there was an increase in the cell’s discharge (41 set latency) which lasted 49 sec. During this excitatory

Fig. 3. Excitatory and inhibitory receptive fields for 28 SMT cells in the upper cervical spinal cord. Areas of the body or face producing excitatory responses to noxious and/or innocuous mechanical stimuli (black) or deep inputs from muscle and/or joints (cross-hatched) are shown on the figurines. Inhibitory receptive fields are also shown (horizontal lines). Receptive fields of cells backfired from both midbrain and thalamus are indicated

with asterisks.

IPSI FOREPAW

IPSI HINDPAW

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Fig. 4. Responses of a wide dynamic range SMT-UC cell to mechanical and thermal stimuli. A-B: responses to BRUSH (1). PRESSURE (2). PINCH (3) and SQUEEZE (4) stimuli applied to the ipsilateral forepaw (A). The cell also responded to noxious thermal stimuli applied to the glabrous skin (B). The 30 set heat pulse increased from an adapt temperature of 35%55’C. C-D: responses to the same stimuli in A and B applied to the ipsilateral hind paw. Note similarity of responses to those obtained from the forepaw. The cell was backfired from a stimulation site in the reticular formation at the intercollicular level of the midbrain (inset), and the recording site was located in the neck of the dorsal horn (lamina V). Durations of stimuli in A-D are represented by the stimulus bars: bin width in A-D is 720 msec.

A

DURA

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Fig. 5. Inhibitory and excitatory responses of two SMT-UC cells. A: inhibitory response to mechanical manipulation of the dura around the superior sagittal sinus. Note constant rate of spontaneous activity that decreaxed and slowly recovered to baseline during the stimulus. Excitatorb responses to squeezing the ipsilateral trapezius muscle are also shown. B: excitatory response of same cell in A to injections (arrows) of 79, sahne (1 ml) into the trapezius muscle. C: inhibitory and excitatory responsea of cell tn A to squeezing the ipsilateral temporalis or trapeztus muscles. respectively. D: excitatory responses of second SMT-UC cell to brushing (BRUSH) or squeezing (SQUEEZE) the skin on the ipsilateral lorepau. E-F: excttatory responses of same cell in D to intravenous injections (arrows) of 30 pg (E) and 100 pg (F) of S-HT. Note elevated background discharge after initial excitation following both doses of drug. Durations of stimuli in A, C. and D are represented by the stimulus bars. Bin width 720 msec in A-F.

period the activity level increased 80% over pre-drug levels (Fig. 5E). The cell’s discharge remained elevated for approximately 2 min before returning to pre-drug levels. In Fig. 5E and F the first 36 set of the histograms were used to compute pre-drug activity levels. Prior to injecting the 100 pg dose of 5-HT the cells spontaneous discharge had increased to the level shown in Fig. 5F. Following the 100 pg dose of 5-HT there was a 70% increase in the cell’s discharge relative to the pre-drug control period. This initial increase was followed by a 10 min interval where the cell’s discharge remained elevated before returning to pre-drug levels (Fig. 5F). Volume matched controls of isotonic saline (vehicle) had no effect on the background activity of this cell. Eight cells were tested for responses to i.v. 5-HT. Two of the 8 cells exhibited excitatory effects and the remaining 6 cells were not affected; 4 of these were also unresponsive to cutaneous or deep input and 2 were classified as deep/tap units. The threshold dose for

excitatory effects of i.v. 5-HT was 5.0 pg. The 2 cells responsive to 5-HT had wide dynamic range response properties with ipsilateral cutaneous RFs on the distal forelimb. i.e., contralateral to the site of drug injection.

Discussion In recent years the results of anterograde [7,74-763 and retrograde [29,45,52,72,74,75,81] tracing studies have provided evidence to establish the spinomesencephalic projection as a multi-component pathway with varied origins. spinal trajectories and sites of termination. The results of these studies have been complemented by reports related to the functional properties of cells antidromically identified from different SMT projection targets [30,31,51,77,78,82,83]. and support the involvement of the SMT in the relay of nociceptive information from cutaneous, muscle, and visceral structures. These conclusions are based exclusively on stud-

193

ies carried out in the lumbosacral spinal cord. To date, no studies have been carried out in the upper cervical cord, a region where nearly 30% of the total SMT cell population is located [81]. In the present study mechanical, thermal and chemical stimuli were used to determine the adequate stimuli required to excite or inhibit SMT cells in the first 3 cervical segments. The results of this study complement and expand those of previous reports related to STT cells [11,28,68] and interneurons [1,59,60] in the upper cervical cord of the cat. In those studies cells were found with cutaneous and deep RFs that often included the hind limbs, tail and oral-facial structures. In the report by Carstens and Trevino [ll], 33% of the cells were classified as ‘widefield’ (spanning more than 2 limbs), whereas 22% had smaller RFs (spanning less than 2 limbs). Trigeminal inputs to upper cervical STT cells were not described in this report [ll]. This is in contrast to the present results as well as other studies [28,68] where oral-facial components of RFs were observed. The presence of trigeminal inputs to upper cervical SMT cells are consistent with the results of Kerr [38] who first described the convergence of trigeminal and spinal volleys on interneurons in the first and second cervical segments. Convergence of trigeminal and neck muscle afferents has also been reported for cells in these segments [1,2]. These reports confirm the overlap between trigeminal afferents and dorsal root projections of the first two cervical segments [2,36-381 and suggest that such convergence may account for atypical craniofacial pain syndromes [37,38]. Furthermore, ‘reports of the favorable effect of blocking the auriculotemporal nerve or upper cervical dorsal roots in tic douloureux may be accounted for on the basis of reduction of afferent stimulation to neurons which receive convergent fibers from both cervical and trigeminal systems’ [361. As described in the present report, and by others [11,28,68], widespread inhibitory RFs are observed for SMT and SIT cells in the upper cervical cord. It is not known if these effects are due to descending influences involving supraspinal structures, spinal mechanisms or both. Previously, it was shown that the complex inhibitory and excitatory responses of lumbosacral SMT [77] and SIT [20,22] cells involve both spinal and supraspinal pathways. Whether the same is true for SMT-UC cells remains to be determined. The present report is the first to describe the responses of SMT cells in the upper cervical cord. As described above, the results are comparable with those reported for cat and primate STT cells, possibly reflecting the general functional organization of this cord level. From these results it is evident that upper cervical SMT and SIT cells are involved in the integration of sensory input that extends beyond the dermatomal organization of the upper cervical cord [26]. Although

the functional significance of these cells in unknown, it is not unreasonable to propose a link between their functional properties and clinical observations following commissural myelotomies in the upper cervical cord. Following this procedure, which potentially disrupts crossing fibers of several ascending pathways, e.g., SIT, SMT, cervicothalamic, post-synaptic dorsal column, and spinoreticular, sensory deficits, including loss of pain, over large portions of the body have been described [27,61]. In addition to the complex RF organization of SMTUC cells, another important issue concerns the anatomical substrate responsible for the relay of input to cervical segments from lower cord levels. Two possibilities include: (a) collaterals of ascending axons; and (b) a spino-bulbo-spinal loop as proposed for lumbosacral SMT [77] and STT [20,22] cells. Consistent with the former possibility are the observations that the responses of cervical SIT cells remained unchanged after spinal lesions sparing the ipsilateral lateral and/or ventral funiculi [ll]. A third alternative that should not be excluded is the existence of an ascending multisynaptic relay. Such a pathway has been shown to have a role in producing vasomotor and respiratory reflexes as well as conditioned responses to visceral and somatic stimuli [6,13,34.40]. The importance of a ‘sensory’ propriospinal relay, however, has been largely ignored due to the focus on the ‘motor’ component of this pathway [33,44,67]. Although not specifically addressed, the present results related to hind limb, tail and genital input to SMT-UC cells suggest that propriospinal circuits may have an important role in the relay of sensory information from lumbar to cervical levels of the cord. Furthermore, reports that cells in the lumbosacral cord are influenced by afferent input to cervical and thoracic segments [9,18,20,22,58,66,77] suggest that this multisynaptic network may have a complementary descending component. In the present study, the convergence of dural input and the responses of cells to i.v. 5-HT are two responses that have not been previously described for projection neurons in the upper cervical cord. Previous studies have shown afferent inputs from the dura, dural vessels, and sagittal sinus to converge on interneurons in the spinal trigeminal complex and cervical cord [14,15,42, 59,711. Furthermore, although these reports emphasize the excitatory effects of dural stimulation, the present results are the first to show that inhibitory effects are also possible. The responses observed in the present study are consistent with dural afferents traveling in the trigeminal nerve [47,57,70], and the termination of trigeminal input in the first 3 cervical segments [36-381. These results also typify the complex convergence and varied origins of inputs to SMT cells at this level of the cord. The responses of SMT-UC cells to i.v. S-HT are

194

particularly interesting in light of the recent report that i.v. 5-HT is a potent noxious visceral stimulus which activates vagal afferents [49]. Supportive of this hypothesis are descriptions of the depolarizing effects of 5-HT on afferent cell bodies in the nodose ganglion [19,65,69], A8 and C fibers in the cervical vagus and inferior cardiac sympathetic nerves [55.56], and extrasynaptic 5-HT receptors on the main vagal trunk [63]. Recently, it was also reported that activation of vagal afferents by i.v. 5-HT produces a vagally mediated bradycardia and hypotension. pseudaffective reactions indicative of pain, and aversive behavior [48-501. lntracoronary injections of 5-HT are also known to produce pseudaffective responses in lightly anesthetized dogs [24.32]. There is. therefore. considerable evidence to support the role of 5-HT in the activation of nociceptive afferents from the heart. Although visceral responses have not been described previously for cells in the upper cervical cord, the present results support the hypothesis that nociceptive information from the heart may converge on SMT cells at this level of the cord. Consistent with this is the similarity of doses used to elicit responses in SMT cells (threshold dose -- 5 pg) and those capable of activating vagal afferents [43,49,50] and fibers in the inferior cardiac nerve [56]. Furthermore. the present excitatory responses to putative vagal afferent activation by 5-HT are similar to effects reported on cells in the thoracic [4,73] and lumbosacral [64] spinal cord following electrical stimulation of vagal afferents. One caveat that should be mentioned, however, is that intra-arterial injections of 5-HT are known to excite cutaneous [25] and group IV muscle afferents [17,41,54]. and craniofacial muscle afferents that converge on neurons in the medullary dorsal horn [3]. Even though the responses of SMT-UC cells were obtained by injections contralateral to excitatory RFs. caution should be used in attributing the action of 5-HT solely to activation of visceral afferents. Additional studies will be needed to identify the afferent population(s) responsible for the action of i.v. 5-HT on SMT-UC cells. In conclusion, results of the present study have shown that the upper cervical component of the cat SMT is made up of a heterogeneous population of cells involved in the integration of varied afferent inputs from different parts of the body. By virtue of the response and RF properties of these cells. it is proposed that the upper cervical cord may constitute an important spinal relay for nociceptive information from cutaneous, muscle. joint and visceral structures.

her time and patience in preparing the manuscript. anti Drs. R. Davidoff, G. Gebhart and .I. Vicedomini for their critical comments. This work was supported by NS19509 (RPY) and by funds from The Miami Project to Cute Paralysis.

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Acknowledgements

The authors wish to thank Carol Mendez for her expert technical assistance, Theresa Whittingham for

I1

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