Comparative Study of Viscerosomatic Input Onto Postsynaptic Dorsal Column and Spinothalamic Tract Neurons in the Primate

Elie D. Al-Chaer,1,2 Yi Feng,2 and William D. Willis2

 1Department of Internal Medicine, Division of Gastroenterology; and  2Department of Anatomy and Neurosciences and Marine Biomedical Institute, University of Texas Medical Branch, Galveston, Texas 77555


    ABSTRACT
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Al-Chaer, Elie D., Yi Feng, and William D. Willis. Comparative Study of Viscerosomatic Input Onto Postsynaptic Dorsal Column and Spinothalamic Tract Neurons in the Primate. J. Neurophysiol. 82: 1876-1882, 1999. The purpose of the present investigation was to examine, in the primate, the role of the postsynaptic dorsal column (PSDC) system and that of the spinothalamic tract (STT) in viscerosensory processing by comparing the responses of neurons in these pathways to colorectal distension (CRD). Experiments were done on four anesthetized male monkeys (Macaca fascicularis). Extracellular recordings were made from a total of 100 neurons randomly located in the L6-S1 segments of the spinal cord. Most of these neurons had cutaneous receptive fields in the perineal area, on the hind limbs or on the rump. Forty-eight percent were PSDC neurons activated antidromically from the upper cervical dorsal column or the nucleus gracilis, 17% were STT neurons activated antidromically from the thalamus, and 35% were unidentified. Twenty-one PSDC neurons, located mostly near the central canal, were excited by CRD and three were inhibited. Twenty-four PSDC neurons, mostly located in the nucleus proprius, did not respond to CRD. Of the 17 STT neurons, 7 neurons were excited by CRD, 4 neurons were inhibited, and 6 neurons did not respond to CRD. Of the unidentified neurons, 23 were excited by CRD, 7 were inhibited, and 5 did not respond. The average responses of STT and PSDC neurons excited by CRD were comparable in magnitude and duration. These results suggest that the major role of the PSDC pathway in viscerosensory processing may be due to a quantitative rather than a qualitative neuronal dominance over the STT.


    INTRODUCTION
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The dorsal column (DC) plays an important role in relaying noxious visceral information to the ventral posterolateral (VPL) nucleus of the thalamus (Al-Chaer et al. 1996a,c, 1998b; Feng et al. 1998). A study done on primates has shown that a lesion of the DC blocks much of the colorectal input into the VPL nucleus (Al-Chaer et al. 1998b). Furthermore, recent results obtained using functional magnetic resonance imaging (fMRI) show that a DC lesion placed at the T10 spinal level dramatically reduces the increases in blood volume observed in thalamic and other brain areas in response to noxious colorectal distension (CRD) (Al-Chaer et al. 1998a,e). Earlier studies done on rats demonstrated that the DC-mediated colon input is largely conveyed in a newly identified component of the postsynaptic dorsal column (PSDC) system, whose cells of origin are in the vicinity of the central canal and whose axons project in the DC (Al-Chaer et al. 1996a,b, 1997b; Hirshberg et al. 1996; C. C. Wang, W. D. Willis, and K. N. Westlund, unpublished observations). Neurons of this newly identified component of the PSDC can be activated by CRD or colon inflammation (Al-Chaer et al. 1996b, 1997b).

Spinothalamic tract (STT) neurons are also known to be involved in visceral sensory processing. The spinothalamic tract arises largely from neurons in the dorsal horn of the spinal cord. The locations of these cells have been mapped in rats, cats, and monkeys using retrograde tracing and antidromic activation methods (see reviews by Hodge and Apkarian 1990; Willis and Coggeshall 1991). Most STT cells studied have cutaneous receptive fields and usually respond to noxious and often also to innocuous mechanical stimulation of the skin (Katter et al. 1996; Owens et al. 1992; Willis et al. 1974). Visceral afferent fibers can activate many STT cells (Ammons et al. 1985; Foreman et al. 1981; see Foreman 1989). STT neurons can be excited by distension of the gall bladder (Ammons et al. 1984), kidney (Ammons 1989a), ureter (Ammons 1989b), or urinary bladder (Milne et al. 1981). Milne et al. (1981) also recorded responses of STT cells in the upper lumbar and sacral segments of the monkey spinal cord to noxious testicular stimulation. These observations form the experimental basis for the assumption that the STT is the major ascending spinal cord tract that conveys information about noxious visceral events to lateral thalamic nuclei.

On the other hand, several research groups have argued for an important role of the DC in visceral input into the VPL nucleus (Apkarian et al. 1995; Berkley and Hubscher 1995; Chandler et al. 1998). In fact, Al-Chaer et al. (1996a, 1997a,c, 1998b) have argued that the DC plays a more important role than that of the STT in relaying information about noxious and innocuous visceral activity into the VPL nucleus in rats and monkeys, because a DC lesion largely blocks colonic input into the VPL nucleus of the thalamus, whereas a lesion that interrupts the STT has much less effect (Al-Chaer et al. 1996a, 1998b).

The purpose of this study was to compare the responses of PSDC and STT neurons in the monkey lumbosacral spinal cord to visceral and somatic inputs. To do this, recordings were made from single, randomly isolated neurons in the L6-S1 spinal segments. These neurons were examined for projections in the DC or the STT and were tested with graded CRD and cutaneous stimuli. Preliminary results of this study have been reported in abstract form (Al-Chaer et al. 1998d).


    METHODS
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Experiments were done on four adult male monkeys (Macaca fascicularis) weighing between 2 and 2.5 kg. The monkeys were sedated with ketamine (10 mg/kg im) and then anesthetized with 4% halothane in a mixture of oxygen and nitrous oxide (30:70%). Tracheal and intravenous cannulae were inserted, and anesthesia was maintained initially by an infusion of alpha -chloralose (60 mg/kg iv) followed by a continuous infusion of pentobarbital sodium (5 mg · kg-1 · h-1). The animals were paralyzed with pancuronium (0.2-0.25 mg · kg-1 · h-1) and artificially respired. A lumbosacral laminectomy was performed to expose the L5-S2 segments of the spinal cord. Cervical laminectomy and removal of part of the occipital bone exposed the upper cervical spinal cord and the caudal medulla. Animals were then transferred to a stereotaxic frame in a shielded recording room, the skin flaps overlying the cord were tied back to form a pool, the dura was cut and reflected to expose the cord, and the pool filled with warmed mineral oil. A craniotomy exposed the cortex above the thalamus. The head was flexed ventrally, the muscles of the neck were retracted, and the dura was cut and reflected to expose the medulla. In one experiment, part of the cerebellum was removed by suction to gain better access to the nucleus gracilis. The adequacy of the depth of anesthesia was evaluated by the examination of the pupillary reflexes, monitoring of the electrocardiogram, and assessing the stability of the expired CO2. A pneumothorax was performed to minimize respiratory movements during recording. End tidal CO2 was maintained at 4 ± 0.5%, and body temperature was kept near 37°C by a thermostatically controlled heating blanket. The arterial blood oxygen saturation level was monitored using a laser oxymeter rectal probe and was kept at 98 ± 2%.

Stimulation

The visceral stimulus used was CRD. It was adapted from the model used in rats (Gebhart and Sengupta 1996; see also Al-Chaer et al. 1996a,b). The stimulus was applied using an inflatable balloon inserted rectally. The balloon was constructed from a latex glove finger attached to a length of a tygon tubing (10 cm). CRD consisted of consecutive inflations of the balloon to pressures ranging between 20 and 80 mmHg, applied in increments of 20 mm for 20 s every 4 min. CRD stimuli having an intensity above 40 mmHg are considered noxious in rats and painful in humans (Ness and Gebhart 1988; Ness et al. 1990).

The cutaneous stimuli employed were brushing (BR) of the receptive field using a camel hair brush, an innocuous stimulus; pressure (PR), using a large arterial clip applied to a fold of skin, a stimulus that causes a sense of near painful pressure if applied to human skin; and pinch (PI) using a small arterial clip that exerts a force of 550 gm/mm2, a distinctly painful stimulus if applied to human skin.

Central stimulation consisted of electrical pulses (200 µs in duration and up to 500 µA in intensity) at a frequency of 2 Hz applied to the CNS to activate projection neurons antidromically. The VPL nucleus was stimulated to identify STT cells. The upper cervical DC or the nucleus gracilis (NG) was stimulated to identify PSDC cells. For VPL nucleus stimulation, a tungsten microelectrode was introduced stereotaxically into the VPL nucleus while recording from the electrode. The tip of the electrode was advanced ventrally while tapping on the perineal area of the body until multiunit activity became distinctly audible on an audio monitor. The coordinates were noted and the electrode was then connected to the stimulator. For stimulation of the upper cervical DC, a ball electrode was placed on the fasciculus gracilis (FG) near the midline, under view through a surgical microscope. Viscerosensitive cells in the sacral cord were isolated and checked for projection in the DC. In one preparation (11 PSDC cells), an extra fine (25 µm tip) tungsten microelectrode was used to map the DCN for terminals or fibers of passage of PSDC cells. This was done to ensure that these neurons were indeed PSDC cells. The stimulating electrode was systematically moved laterally from the midline in increments of 100 µm at different transverse planes separated by 100 µm and spanning a rostrocaudal length of 8 mm centered at the obex. The electrode was advanced ventrally in 100-µm steps until a minimal antidromic threshold was recorded. The antidromic threshold at each site in the penetration was defined as the current that produced an action potential in ~50% of the trials. The electrode was moved until the PSDC unit was activated antidromically with currents <= 30 µA. Current pulses of 30 µA spread <400 µm (Ranck 1975). The locations from which PSDC neurons were activated antidromically with currents <= 30 µA were marked by an electrolytic lesion. Responses were considered to be antidromic if they fulfilled three criteria: constant stimulus-response latency, following of high-frequency stimuli (300-500 Hz), and collision of the evoked spike with orthodromic spikes at appropriate intervals.

Recordings

Recordings were made from single units isolated at the L6-S1 segmental level using carbon fiber glass microelectrodes. Small holes were made in the pia mater, under view through a surgical microscope and using fine forceps to facilitate the introduction of the recording microelectrode. All units were examined for projections into the DC or the VPL nucleus and also for peripheral somatic and visceral inputs. During the search process, the recording electrode was driven into the spinal cord while electrical stimuli were simultaneously applied in the VPL nucleus (to activate STT neurons antidromically) and to the DC (to activate PSDC neurons antidromically). Every neuron encountered was examined for possible antidromic activation from either the VPL nucleus or the DC separately. All neurons recorded in this sample were checked for input from the colon using CRD as the stimulus. Then all neurons were examined for cutaneous input using three different modalities (Brush, Press, and Pinch). Units that responded to CRD were classified as viscerosensitive, units that were antidromically activated from the DC or the DCN were considered to be PSDC neurons, and units antidromically activated from the VPL nucleus were regarded as STT neurons. Units that were not activated antidromically from either the DC or the VPL nucleus were considered to be unidentified neurons.

The extracellular action potentials recorded were fed into a window discriminator and displayed on an oscilloscope screen. The output of the window discriminator was led into a data collection system (CED 1401+) and a personal computer to compile rate histograms or wavemark files using the Spike 2 software program. The response to each intensity of CRD was stored separately. Twenty seconds of baseline activity preceded the application of a distension stimulus. Each stimulus lasted 20 s. Four minutes were allowed to elapse between two consecutive CRDs. The responses are expressed as the average rate of firing of the cell during a particular stimulus minus the average baseline rate.

Histology

At the end of each experiment, a continuous current (1 mA for 20 s) was passed to mark the stimulation sites in the VPL nucleus and in the NG. The tip of the carbon fiber glass microelectrode was cut off and left at the recording site. The spinal cord at the level of the recordings and the brain were removed and put into a neutral Formalin solution (4%). The tissues were stored in 20% sucrose before frozen sectioning at 50 µm. The recording and stimulation sites were later identified histologically.

Statistics

The CRD data were analyzed using a repeated measures ANOVA. A model with the repeated factor of intensity, group, and the (intensity × group) interaction showed that there was a significant intensity effect (P < 0.001), no group effect (P = 0.67) and no (intensity × group) interaction (P = 0.12). The interpretation of these results is that there was a significant increase in the magnitude of neuronal responses across levels of CRD for all three groups. The nonsignificant group and interaction effects mean that responses in all three groups increased in a similar fashion.

The responses to cutaneous stimuli (Brush, Press, and Pinch) were first analyzed using an overall test (Hotelling's T2 test) to assess the extent to which the distributions of these three variables differed across all three groups (PSDC, STT, and Unidentified), when considered simultaneously. This test showed a significant difference across groups (P = 0.038), and subsequent one-way ANOVAs showed that only the variable Press showed an overall difference among the three groups (P = 0.002). Tukey's Studentized range test showed that groups STT and PSDC differed significantly, with a difference of means of 33.6 spikes/s (95% CI: 12.9, 54.2).


    RESULTS
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

A total of 100 neurons were isolated in the L6-S1 segments of the spinal cord. The neurons were distributed between 400 µm and 2 mm in depth measured from the surface of the spinal cord. The mediolateral distribution extended from near the dorsal median septum to the edge of the dorsolateral funiculus. The recording sites were reconstructed by extrapolating their locations from distance parameters recorded in relation to marked sites as shown in Fig. 1.



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Fig. 1. Drawing of a cross-section through S1 illustrating recovered recording sites. , postsynaptic dorsal column (PSDC) neurons that responded to colorectal distension (CRD); open circle , PSDC neurons that did not respond to CRD; , spinothalamic tract (STT) neurons that responded to CRD; , STT neurons that did not respond to CRD.

Neuronal characteristics

All isolated neurons were tested for projections into the DC and into the VPL nucleus. They were also tested for responses to cutaneous stimulation and to CRD. The neurons were then grouped into three categories based on whether they could be antidromically activated by DC stimulation, by stimulation of the VPL nucleus or by neither. The responses of neurons within each category were analyzed separately. Table 1 illustrates the number of neurons in each category according to their responses to CRD.


                              
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Table 1. Types and responses of neurons recorded in this study

Neurons activated by CRD exhibited an increase in their responses that correlated with the increase in stimulus intensity. The population stimulus response curve was approximated by a linear regression for all the neurons in each category. These regression lines show that the rate of change (slope) was similar across neuronal types (Fig. 2: PSDC, STT, and Unidentified). This graded response was observed regardless of the threshold of activation of the VPL unit by CRD. The threshold of activation was defined as the lowest intensity of CRD that evoked a neuronal response and was determined with increasing steps of 20 mmHg of intracolonic pressure for the cells tested. The accuracy is estimated to be 10 mmHg across the pressure spectrum (20-80 mmHg). The average thresholds of activation for neurons of each category are illustrated in Fig. 3.



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Fig. 2. Approximation of the population stimulus response by a linear regression for all the excited PSDC neurons (A; n = 21; r = 0.3), STT neurons (B; n = 7; r = 0.5), and unidentified neurons (C; n = 9; r = 0.6). The linear regressions indicate a correlation between the response and the stimulus intensity; r is the correlation coefficient. r2 is sometimes called the coefficient of determination and is a measure of the closeness of fit of a scatter graph to its regression line. Confidence intervals, also called the confidence interval for regression, describe the range where the regression line values will fall 95% of the time for repeated measurements. Prediction intervals, also called the confidence interval for the population, describe the range where the data values will fall 99% of the time for repeated measurements.



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Fig. 3. Graph illustrates the distribution of threshold intensities of CRD for excited PSDC, STT, and unidentified neurons. The mean thresholds were 34 ± 3.9 mmHg for PSDC neurons (n = 24), 31 ± 5.9 mmHg for STT neurons, and 43.4 ± 3.4 mmHg for unidentified neurons (n = 30); (mean ± SE; range 20-80 mmHg). The vertical box plot displays the median, 10th, 25th, 75th, and 90th percentiles as the boxes with error bars and the 5th and 95th percentiles as small circles (the percentile increases downward).

PSDC NEURONS. Of 100 neurons isolated, 48 were antidromically activated by stimulation of the DC. In one preparation, nine PSDC neurons were antidromically activated by low-intensity stimulation in the NG (as low as 10 µA). The PSDC neurons could be classified into two clearly separable populations. One group of relatively shallow neurons (n = 24; <1,400 µm in depth) located mostly near the lateral edge of the pia hole was unresponsive to CRD. A second group of relatively deep neurons (n = 24; >2 mm) located mostly near the midline responded to CRD. Twenty-one neurons were excited and three neurons were inhibited (Table 1). Of the 24 viscerosensitive PSDC neurons, 22 had cutaneous receptive fields located on the inner and posterior aspects of the thigh, on the rump, or on the scrotum. Two PSDC neurons excited by CRD could not be activated by skin stimulation. Of the 24 PSDC neurons that did not respond to CRD, 12 neurons had cutaneous receptive fields located over the outer aspect of the leg, the upper thigh, and the rump, and 12 could not be activated by somatic stimulation. The responses of viscerosensitive PSDC neurons to CRD were graded with stimulus intensity (Fig. 2A). The mean threshold for activation of PSDC neurons was 34 ± 3.9 (SE) mmHg (Fig. 3). The average response to 20 mmHg was 4.6 ± 1.9 spikes/s, and the average response to 80 mmHg was 17.4 ± 3.5 spikes/s (Fig. 4). The average responses to cutaneous stimulation did not show any major differences between types of stimuli, although there was a trend for the responses to Brush stimuli to be greater than those to Press or Pinch stimuli (Fig. 5). Figure 6 illustrates the site of recording of a PSDC neuron, the site of stimulation for antidromic activation in the NG, the antidromic spikes, and the responses of the PSDC neuron to CRD and cutaneous stimulation.



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Fig. 4. Line graphs illustrating the average responses, in spikes/s, of 13 PSDC neurons, 8 STT neurons, and 9 unidentified neurons excited by CRD. No significant differences were seen between the 3 groups.



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Fig. 5. Bar graphs illustrating the average responses, in spikes/s, of 13 PSDC neurons, 12 STT neurons, and 4 unidentified neurons to cutaneous stimulation of their respective receptive fields. * Significant difference between the responses of PSDC and STT neurons to pressure.



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Fig. 6. A: rate histograms of the responses of a PSDC neuron to cutaneous stimulation (BR, brush; PR, press; PI, pinch). The stimuli were applied for 10 s each. B: trace of the antidromic spike triggered by stimulation within the dorsal column nuclei. C: collision of the antidromic spike with an orthodromic spike evoked by stimulation of the receptive field. Dot indicates the predicted time of the antidromic spike. D: traces of spikes illustrating a constant latency and following high-frequency antidromic stimulation. E: drawing of a cross-section through the lower medulla showing the gracile nuclei. Dot indicates the site of antidromic stimulation. F: drawing of a cross-section through the lumbosacral spinal cord at S1 illustrating the recording site of a PSDC neuron. G: rate histograms of the responses of a PSDC neuron to graded colorectal distension (CRD). H: trace of the spike recorded.

STT NEURONS. Seventeen isolated neurons were antidromically activated by stimulation in the VPL nucleus. The depth of these neurons ranged between 1 and 2 mm from the surface of the pia hole, and most of them were best isolated at the lateral edge of the pia hole near the dorsolateral funiculus. Of the 17 STT neurons, 7% were excited by CRD, 4% were inhibited, and 6% did not respond to CRD. Fifteen STT neurons could be activated by cutaneous stimulation applied to the back and inner aspect of the thigh, to the scrotum, and to the perineal area. The responses of viscerosensitive STT neurons to CRD were graded with stimulus intensity (Fig. 2B). The mean threshold for activation of STT neurons was 31.4 ± 5.9 mmHg (Fig. 3). The average response to 20 mmHg was 6.8 ± 4 spikes/s, and the average response to 80 mmHg was 20.6 ± 7.2 spikes/s (Fig. 4). The STT cells responded better to Press or Pinch than to Brush stimuli applied to the cutaneous receptive field (Fig. 5). Figure 7 illustrates the site of recording of an STT neuron, the site of stimulation for antidromic activation in the VPL nucleus, the antidromic spikes, and the responses of the STT neuron to CRD and cutaneous stimulation.



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Fig. 7. A: rate histograms of the responses of an STT neuron to cutaneous stimulation (BR: brush; PR: press; PI: pinch). The stimuli were applied for 10 s each. B: trace of the antidromic spike triggered by stimulation of the VPL nucleus of the thalamus. C: collision of the antidromic spike with an orthodromic spike evoked by stimulation of the receptive field. The dot indicates the predicted time of the antidromic spike. D: traces of spikes illustrating a constant latency and following high-frequency antidromic stimulation. E: drawing of a cross-section through the lumbosacral spinal cord at S1 illustrating the recording site of the STT neuron. F: rate histograms of the responses to graded colorectal distension (CRD). G: trace of the spike recorded.

UNIDENTIFIED NEURONS. Thirty-five neurons encountered could not be activated antidromically from either the VPL nucleus or the DC and were classified as unidentified neurons. Twenty-three of these neurons were excited by CRD, seven were inhibited, and five did not respond to CRD. The responses of these neurons to CRD were comparable to the responses of PSDC and STT neurons. Twenty-four of these neurons could be activated by cutaneous stimulation applied to the back of the leg, the inner thigh, the rump, or the perineal area. The responses of the viscerosensitive unidentified neurons to CRD were graded with stimulus intensity (Fig. 2C). The mean threshold for activation of these neurons was 43.4 ± 3.9 mmHg (Fig. 3). The average response to 20 mmHg was 3.3 ± 1.4 spikes/s, and the average response to 80 mmHg was 21.6 ± 3.8 spikes/s (Fig. 4). There was a tendency for the responses to Press and Pinch stimuli to exceed those to Brush stimuli (Fig. 5).


    DISCUSSION
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The results obtained in this study do not reveal any major differences between the nature and characteristics of the responses of PSDC, STT, and unidentified neurons to CRD. The average responses and the threshold for activation of each neuronal category were not significantly different. Individual responses were stimulus-bound and graded with stimulus intensity. The only major difference noticed was the number of neurons isolated within each category. The neurons were isolated on a random encounter basis during simultaneous search stimulation of the DC and of the VPL nucleus. They were then tested for visceral and cutaneous responses and for specific projections into the VPL nucleus or into the DC. No neurons with double projections were encountered. The PSDC neurons isolated at L6-S1 spinal levels outnumbered the STT cells and the unidentified neurons. This numerical predominance of PSDC neurons that respond to CRD may underlie the greater role of the DC in transmitting colonic input into the VPL nucleus than the STT as was shown in a recent study by Al-Chaer et al. (1998b). A lesion of the DC at the T10 segmental level dramatically reduced the responses of VPL neurons to CRD, whereas the effects of anterolateral or dorsolateral spinal lesions were not as consistent and dramatic as those of a DC lesion. Earlier observations in the rat (Al-Chaer et al. 1996a) showed that the visceral input in the DC is conveyed largely by the axons of PSDC neurons (Al-Chaer et al. 1996b), whose cell bodies are located mainly around the central canal (Hirshberg et al. 1996). These axons converge onto gracilothalamic neurons (Al-Chaer et al. 1996b), which presumably relay the majority of pelvic visceral input from the colon to the VPL nucleus (Al-Chaer et al. 1997a).

In most mammalian species, the VPL nucleus receives sensory information arising from stimulation of the skin, deep tissues, and viscera and conveyed over two major ascending tracts: the dorsal column pathway and the spinothalamic tract. Some of this information can also be conveyed through the spinocervical tract and also other indirect pathways relaying through neurons of the brain stem reticular formation that receive input from fibers traveling in the ventrolateral quadrant (Willis and Coggeshall 1991). Although spinoreticular neurons may respond to visceral stimuli (e.g., Blair et al. 1984), it is not known whether visceral input can be transmitted indirectly by this pathway to the VPL nucleus.

A considerable amount of research has been done on the response characteristics of STT neurons and of PSDC neurons and neurons of the DC nuclei (Willis and Coggeshall 1991). However, very little has been done to characterize potential differences in the response properties of these different populations of projection neurons (Brown et al. 1986; Chandler et al. 1998). In a recent study in monkeys, Chandler et al. (1998) described differences in the evoked discharge rates, latencies to activation and duration of peristimulus histogram peaks between cuneothalamic and STT neuronal responses to cardiopulmonary sympathetic input. They suggested that dorsal and ventrolateral pathways to the VPL nucleus of the thalamus play different roles in the transmission and integration of nociceptive cardiac information. Cuneothalamic neurons are not the anatomic equivalent of STT neurons. Therefore the differences seen by Chandler et al. may be due to different organizations of a spinal pool of neurons (STT) and a supraspinal pool (DCN). In this study, we compare two different populations of projection neurons, both of which are located in the spinal cord, at the level of convergence of colon afferents. In addition, there may be differences in the nature of the input received by each pathway. These may arise out of differences between the stimuli used (natural colon stimulation vs. electrical stimulation of cardiothoracic afferents) or differences in the type of receptors innervating the colon and the heart.

In the present study, the location of viscerosensitive PSDC neurons corresponded well with the location of viscerosensitive PSDC neurons observed previously in the rat (Honda 1985; Ness and Gebhart 1987). The vast majority of these neurons were in and around the central canal. PSDC neurons isolated elsewhere in the spinal cord, mainly in more superficial layers of the dorsal horn, were not responsive to CRD. The distributions of visceroceptive PSDC neurons correlate with the site of convergence of pelvic nerve terminals (Nadelhaft et al. 1983). The STT neurons encountered were not as abundant as PSDC neurons. The distribution of STT neurons corresponded with findings of previous studies from this laboratory (Willis et al. 1979). Unidentified viscerosensitive neurons were also distributed throughout the area of gray matter explored.

Careful analysis of the response characteristics of each group of neurons to CRD did not reveal any differences in the attributes of these responses. The responses were stimulus bound and graded with the stimulus intensity. No significant differences in the amplitude of the responses to each individual stimulus were seen; in addition, the slopes of the stimulus-response curve for each type of neuron were not significantly different. These observations reduce the likelihood that the predominant role of the DC in visceral input into the thalamus can be attributed to stronger responses of individual viscerosensitive PSDC neurons and argues for a stronger collective input of the PSDC system compared with other ascending spinal pathways. Even though the characteristics of the neuronal responses could differ were we to use a different stimulus (Chandler et al. 1998), the effect of a DC lesion remains consistent with a stronger DC input.

Putative roles for each system

These various pathways may be anatomically separate, but they are by no means independent (Zhang et al. 1996). Disruption of the information flow in one of them may alter the function of the other (Saadé and Jabbur 1984). So how could one extrapolate a limited physiological function into a global sensory role? In a situation where the perceived stimulus is localized in time and brief in duration, a linear flow of information is a plausible hypothesis even though it may be incomplete. However, when dealing with situations of chronic pain or sensory loss, many variables come into play, among them the dynamic interplay between the various neuronal components (Berkley et al. 1993; Chandler et al. 1996; Le Bars et al. 1979; see also Bouhassira et al. 1998), the wind-up of activity within each component (Al-Chaer et al. 1996c, 1997a,b; Roza et al. 1998); and the rewiring of the nervous hardware when necessary. The abundance of PSDC neurons in lumbosacral segments of the cord affords the PSDC system the ability to manage the peripheral input at that level and to relay it to other neurons within those segments and to higher neuronal structures.

In summary, the results of this study show that the PSDC system plays an important role in the processing of innocuous and noxious colorectal information in the monkey. This role may be based largely on the number of viscerosensitive PSDC neurons encountered at L6-S1 segments. This is not to discount the role of other ascending pathways such as the STT, but the data obtained suggest that STT cells are less abundant in those segments than PSDC cells. We can only speculate about the role of unidentified neurons. Therefore similar to what we have seen in rats (Al-Chaer et al. 1996b), we conclude that the neuronal basis for the role of the DC in colon pain (Al-Chaer et al. 1998b) rests largely on the PSDC system.


    ACKNOWLEDGMENTS

The authors thank K. Gondesen for assistance with the surgical procedures and G. Gonzales for assistance with the artwork.

The experiments were supported by National Institute of Neurological Disorders and Stroke Grants NS-11255 and NS-09743.


    FOOTNOTES

Address for reprint requests: W. D. Willis, Dept. of Anatomy and Neurosciences, Marine Biomedical Institute, 301 University Blvd., Galveston, TX 77555-1069.

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 29 January 1999; accepted in final form 29 June 1999.


    REFERENCES
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

0022-3077/99 $5.00 Copyright © 1999 The American Physiological Society