through the dorsolateral funiculus (DLF) and the ventrolateral quadrant (VQ) of the ... ventral posterior lateral nucleus (VPL) of the thalamus. Their locations ...
JOURNALOFNEUROPHYSIOLOGY Vol. 64, No. 5, November 1990. Printed
in U.S.A.
Ventrolateral and Dorsolateral Ascending Spinal Cord Pathway Influence on Thalamic Nociception in Cat ROBERT J. MARTIN, A. VANIA APKARIAN, AND CHARLES J. HODGE, JR. Department of Neurosurgery, State University ofNew York Health Science Center at Syrucuse, Syracuse, New York 13210
SUMMARY
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CONCLUSIONS
INTRODUCTION
1. In cat there are two portions of the spinothalamic tract w-n -a ventral component, the ventral spinothalamic tract (VSTT) made up of axons of cells of spinal cord laminae IV-X, and a dorsolateral component, the dorsolateral spinothalamic tract (DSTT) made up of axons of cells in lamina I of the spinal cord dorsal horn. This study was designed to evaluate thalamic neuronal responses to cutaneous noxious thermal stimuli and to determine the functional importance of pathways ascending in the ventral and dorsolateral portions of the spinalcord, ipsilateral to the thalamic recording site and contralateral to the hindlimb stimulation region,for transmissionof nociceptiveinformation to the thalamus. 2. Extracellular single-unit recordings were made from 45 neurons in the ventrobasal complex (VBX) of cat thalamus. Thirty-five of theseunits respondedeither exclusively or preferentially to noxious cutaneousstimuli. Responses to noxiousthermal stimuli applied to the unit’s receptive fields were obtained, and then the effects on these responsesof blocking conduction through the dorsolateralfuniculus (DLF) and the ventrolateral quadrant (VQ) of the thoracic spinal cord ipsilateral to the thalamic recording site were determined. DLF and VQ conduction blockswere accomplishedwith the useof a cold probe technique and, at times, surgicallesionsof the appropriate portion of the spinalcord. 3. The nociceptive units were located in the periphery of the ventral posterior lateral nucleus (VPL) of the thalamus. Their locations corresponded to the somatotopic organization of VPL.
Nociceptive thermal responses werefound in both high-threshold (HT) ( 10 cells)and wide-dynamic-range(WDR) (22 cells)units. The receptive fields of these units were generally small and were located on the hindlimb contralateral to the recording site. The
The importance of the anterolateral quadrant of the spinal cord for the rostra1 transmission of nociceptive and thermal information was established originally by clinical observations (Brown-Sequard 1868a,b; Gowers 1878; Spiller 1905). Based on these observations, surgical destruction of the spinal cord anterolateral quadrant was tried (Spiller and Martin 19 12) and established (Foerster and Gage1 1932; Horrax 1929; Nathan 1963; White and Sweet 1969) as an effective treatment for clinically intractable pain. The existence of crossed ventral pathways transmitting nociceptive information has been supported by studies demonstrating loss of pain and temperature discrimination in primate and human after section of the spinal cord anterolateral quadrant (Foerster and Gage1 1932; Greenspan et al. 1986; Vierck and Luck 1979; White and Sweet 1969), the production of clinical pain by ventral quadrant (VQ) stimulation in human (Mayer et al. 1975; Tasker et al. 1976), and the rostra1 transmission of pain in a patient with only a single VQ intact (Noordenbos and Wall 1976). In cat, pathways ascending at the VQ-dorsolateral funiculus (DLF) border are important for temperature discrimination (Norrsell 1979), and DLF pathways are important for nociception (Casey and Morrow 1988; Kennard 1954). Pathways ascending in the VQ of primate and cat terminate in widespread areas of the thalamus, including the ventral posterior lateral (VPL) nucleus, as well as in the brain stem (Apkarian and Hodge 1989d; Apkarian et al. 1987; Applebaum et al. 1979; Berkley 1980, 1983; Boivie 197 1, 1979; Bowsher 1957; Craig and Burton 1985; Getz 1952; Le Gros Clark 1936; Mantyh 1983; Mehler 1969; Mehler et al. 1960; Walker 1940). An important difference between cat and primate is the relative lack of spinothalamic tract (STT) terminations in the core of cat VPL. Further evidence that a STT, made up of axons from
thermoreceptive units had thresholdsbetween44 and 48°C and were able to codefor stimulusintensity. 4. Nine of the 35 nociceptive units demonstrateda decreasein responseand two units an increasein responseto noxious cutaneousstimulation during DLF block ipsilateralto the recordingsite and contralateral to the cutaneousstimulation site,whereasfour units demonstrated a decrease in responseand one unit an increasein responseto noxious thermal cutaneousstimulation dur- cells of the contralateral spinal cord grey matter, ascendsin ing VQ block ipsilateral to the recording site and contralateral to the VQ of the spinal cord has been supplied by studies the cutaneousstimulation site. None of the units that showeda demonstrating retrograde activation of lumbar spinal cord decreasedresponsivenessduring VQ block also showeda de- VQ fibers by thalamic stimulation (Applebaum et al. 1975) creasedresponsiveness during DLF block, and none of the units and the presence of labeled axons in the VQ after thalamic (Apkarian and Hodge that showeda decreasedresponsiveness during DLF block also horseradish peroxidase injection showeda decreasedresponsiveness during VQ block. 1989b; Jones et al. 1987). The finding that spinal cord 5. Theseresultsindicate that nociceptive information is trans- lamina I cells, the most uniformly nociceptive-specific cell mitted rostrally through both the DLF and the VQ, supporting group in the spinal grey matter of cat (Christensen and Per1 the hypothesisthat the DSTT is a potentially important nocicep- 1970), contribute to the STT (Carstens and Trevino 1978; tive pathway.
Craig and KnifIki 1985; Craig and Burton 198 1; Giesler et al. 198 1; Trevino et al. 1973, 1974; Willis et al. 1978, 1979)
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seemed to solidify the role of the STT in the VQ as the major ascending nociceptive pathway. Several clinical and experimental findings raise doubt about the exclusive role of VQ pathways in nociception. For instance, even after successful human cordotomies, electrical skin stimulation below the level of the lesion could still be recognized as painful (King 1957), and -50% of patients with an initial successful cordotomy developed return of pain perception in the analgesic area over the course of 12 mo (White and Sweet 1969). These findings have prompted the search for “alternate pain pathways.” Candidates for this role have included the spinocervical tract, the postsynaptic dorsal column pathway, and the dorsal columns and central propriospinal pathways (Albe-Fessard et al. 1985; Besson and Chaouch 1987; Vierck et al. 1985; White et al. 1950). Little attention has been paid to the idea that the STT might extend beyond its classical confines in the VQ. Kuru (1949) postulated the existence of a dorsolateral spinothalamic tract (DSTT) located at the border of the VQ and DLF as well as more dorsally, transmitting thermal and nociceptive information, originating from lamina I cells in human. Lamina I axons project rostrally primarily in the DLF in both rat (McMahon and Wall 1983) and cat (Apkarian et al. 1985). In an extension of this work, Jones et al. (1985, 1987) and Stevens et al. (1989) found, in cat, that lamina I cell input to the thalamus ascends in the DLF contralateral to the cells of origin and ipsilateral to the thalamic termination site. Similar findings have been reported for primate (Apkarian and Hodge 1989a,c). Therefore there are two spinothalamic pathways, a ventral spinothalamic tract (VSTT) made up of axons of cells in contralateral spinal laminae IV-X and a DSTT made up of axons from cells located in contralateral spinal lamina I (Apkarian and Hodge 1989a,c; Jones et al. 1987). The purpose of this study was to determine the relative contribution of information transmitted rostrally, through the VQ (including the VSTT) and the DLF (including the DSTT), contralateral to the cutaneous stimulation site and ipsilatera1to the thalamic recording site, to lateral thalamic nociceptive responsive neurons in cat. METHODS
Adult cats weighing between 2.5 and 3.5 kg were used for these experiments. After induction of anesthesia with intravenous pentobarbital sodium (Nembutal) (35 mg/kg), tracheal, arterial, and venous cannulae were placed; the animal was placed in a spinal frame and stereotactic head holder, and mechanical ventilation was instituted with 30% oxygen and 70% nitrous oxide. Supplemental halothane, 0.2-OS%, was used as needed to maintain anesthesia characterized by slitlike pupils and an absence of all withdrawal reflexes in response to surgical stimuli. Systolic blood pressure was maintained between 80 and 150 Torr, and end expiratory CO2 was kept between 3 and 5%. Body temperature measured with an esophageal thermometer was maintained between 36 and 38°C. A small parietal craniectomy was done for electrode access to the thalamus, and a three-level midthoracic laminectomy was done to gain access to the thoracic spinal cord. The dura was opened over both areas and the exposed neural tissue covered with warm mineral oil. The dentate ligament of the exposed thoracic spinal cord was sectioned. Dural sutures were used to gently rotate the thoracic spinal cord, allowing visualization of the ventrolateral cord surface. The animal was given intra-
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venous gallamine triethiodide as needed to suppress spontaneous respirations. Ample time (2 h) was allowed to elapse between gallamine triethiodide doses to be sure that no nocifensive reflexes were masked by the paralyzing agent. Parylene-coated tungsten microelectrodes with impedances of l-3 Mfi were used to record single-unit activity in the lateral thalamus. The initial target area for recording-electrode placement was the lateral border of the ventrobasal complex (VBX) determined from the atlas of Berman and Jones (1982). The lateral thalamus was explored until the hindlimb portion of the VBX was encountered. Systematic electrode penetrations were then made until a unit with nociceptive response characteristics was found. Nociceptive units were difficult to find in this preparation, it being a common experience for us to examine > 100 units for each nociceptive unit found. The electrode depth was adjusted such that an action potential of stable amplitude could be clearly distinguished from background activity. Once a unit was isolated, its responsiveness to graded cutaneous stimuli was evaluated. These stimuli included light brushing of hairs, gentle pressure with a blunt stylet, muscle pressure and joint movement, and finally pinch with serrated forceps, which was clearly painful when applied to the experimenters. Receptive-field sizes and locations were then determined, and lastly the response of the unit to cutaneous heating to >45”C was determined. The cutaneous heating was done with a contact Peltier thermode, the temperature of which could be varied from 5 to 55°C. Units were characterized as low threshold (LT) if they responded to innocuous stimuli and did not increase activity with clearly noxious stimuli. They were characterized as wide dynamic range (WDR) if they responded to innocuous stimuli and had a greater response to clearly noxious pinch. They were characterized as high threshold (HT) if they responded to only noxious mechanical or thermal skin stimuli (Hodge et al. 1983). A window discriminator was used to convert single action potentials to uniform pulses. The times of occurrences of the pulses were stored by the use of a Hewlett-Packard lOOO/A900 computer. In addition, the computer was used to control the temperature sequences of the Peltier thermode used for skin stimulation. The Peltier stimulating temperature was collected simultaneously with the spike time data allowing later construction of peristimulus time histograms. Control responses of the nociceptive thalamic unit to repetitive temperature steps, starting at innocuous levels and progressing to noxious levels (>45”C), were collected with at least a 5-min interval between trials. When a stable response was obtained, the effect of blocking transmission (see below for details of VQ and DLF blocking) through either the VQ or the DLF, ipsilateral to the recording site and contralateral to the cutaneous stimulation site, on the response to the same cutaneous temperature sequence was determined. The cold block was then removed and repeated trials done until stable control responses returned, and then blocking transmission through the untested quadrant (VQ or DLF) was done. Final control trials were then done. This sequence was frequently repeated several times to determine the consistancy of the cold-block effects. The data were displayed either as peristimulus time histograms or as mean or maximum unit firing rate compared with stimulus temperature. The location of each successful recording site was marked with a small electrolytic lesion. After completion of each experiment, the brain was removed, fixed in Formalin, sectioned, stained with cresyl violet, and the recording sites determined histologically. A maximum of four units was collected from each animal. The blocking technique used in these experiments is described in a separate publication (Apkarian et al. 1989). An adaptation of the method described by Salsbury and Horel (1983) was used. Twenty-six guage stainless steel tubing was bent to an appropriate shape to fit against the feline spinal cord. Through this tubing was
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FIG. 1. Locations of 35 cells displayed on schematic hemisections of the cat thalamus. Legend refers to effects of cooling the ipsilateral DLF or VQ on cells’ responses to peripheral noxious cutaneous stimulation. Numbers in the bottom ~@zt of each section refer to the AP plane of that section. Abbreviations are as following: AD, anterior dorsal nucleus; AM, anterior medial nucleus; AV, anterior ventral nucleus; CeM, central medial nucleus; CL, centrolateral nucleus; CM, centromedian nucleus; H, habenula; LD, lateral dorsal nucleus; LGN, lateral geniculate nucleus; LP, lateral posterior nucleus; PC, paracentral nucleus; Pf, parafascicular nucleus; Porn, medial portion of posterior nucleus; MD, medial dorsal nucleus; PUL, pulvinar; RE, reticular nucleus; SM, nucleus submedius; SN, subthalamic nucleus; VA, ventral anterior nucleus; VBvp, ventral periphery of ventral basal complex; VL, ventral lateral nucleus; VM, ventral medial nucleus; VPL, ventral posterior lateral nucleus; VPLl, lateral portion of VPL; VPLm, medial portion of VPL; VPM, ventral posterior medial nucleus; Zi, zona incerta.
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pumped methanol cooled by passage through a dry ice-methanol bath. The DLF and VQ probes were placed - 1S-2.0 mm apart such that the DLF probe was located just lateral to the dorsal root entry zone, and the VQ probe was located halfway between the dentate ligament and the exit of the ventral roots. Because the purpose of this paradigm was to evaluate the effects of blocking transmission through the VSTT and the DSTT, the probes were placed ipsilateral to the thalamic recording site and contralateral to the receptive field of the unit under study. The temperature of the tubing in contact with either the VQ or the DLF of the spinal cord was monitored with a thermistor and could be varied between the oil bath temperature (35°C) and O°C to accomplish the
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conduction block. Prior experiments in this laboratory have shown that at a probe temperature of 0°C the 10°C isothermal line encompassed an area extending radially 1 mm from the cold probe (Apkarian et al. 1989). This then would be the maximum blockable area, because myelinated peripheral fibers are blocked at 7.2 t 3.0°C (SE) (Franz and Iggo 1968). This technique is capable of repeatedly and reversibly blocking dorsal column fiber activity. With the use of this method, transmission through some -but not all-ascending axons of lamina I cells can be reversibly blocked by the DLF probe (Apkarian et al. 1989). These axons are not affected by the VQ probe (Apkarian et al. 1989). In some animals microsurgical lesions were used to interrupt transmission
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FIG. 2. Schematic representations of cat hindlimbs demonstrating receptive fields of thalamic cells from which recordings were made. Legend refers to the type of stimuli that caused an increase in the firing rate of the cell. Figurines are grouped according to the cell classification (LT, WDR, HT).
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through various thoracic spinal cord funiculi. The extent of these lesions was determined with the use of a 1~x01 fast-blue stain for myelin. RESULTS
Forty-five cells from 20 cats were studied. Of these cells, 10 were LT units, 25 were WDR units, and 10 were HT UIihS. The LT units were chosen based on their location near HT or WDR units, thus placing them in locations most likely to be affected by alterations in STT input. All of the HT and 22 of the 25 WDR units responded to noxious thermal (~45 “C) cutaneous stimulation. Noxious pinch was used to activate the three remaining WDR units. Forty-one of the units were studied with the use of the cold-probe funicular blocking technique; four were studied with the use of surgical spinal cord lesions, and three were studied with the use of both techniques to interrupt transmission in limited areas of the spinal cord. Cell characteristics and locations The locations of 35 of the recording sites could be determined with confidence and are illustrated in Fig. 1. Thirtythree of the units were located on or very near the periph-
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ery of and within the VPL nucleus of the thalamus. All units the recording sites of which were marked with an electrolytic lesion and were recovered histologically were located on the periphery of VPL. Those recording sites indicated to be within VPL were all determined by extrapolation from other recording-site lesions. Most of the recording sites were in the ventrolateral periphery of VPL. Two units were located in the medial portion of the posterior nuclear group (Porn) of the thalamus. There was no particular segregation of the locations of the HT units compared with the WDR units. Figure 2 illustrates the receptive-field sizes and locations of the units studied. The major portions of all the receptive fields were located on the contralateral hindlimb. The fields of the units located at the periphery of VPL were generally small, though the receptive fields of the WDR and HT units were larger than the fields of the LT units. The borders of the responses of WDR units were larger for innocuous stimulation than for noxious stimulation with a single exception. Two of the peripheral VPL units had receptive fields that extended across the midline. The two WDR units located in POm had bilateral receptive fields. The control responses of the WDR and HT units to noxious thermal stimulation are illustrated in Fig. 3. There
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FIG. 3. Top plots are response curves of individual cells grouped according to cell type, WDR on the Iefi and HT on the right. Each point represents the mean response (spikes/second) of a single unit to the cutaneous temperature (indicated on the ordinate) applied to the cell’s receptive field. Bottom plots are averaged response curves of all WDR (left) and HT neurons (right) with a superimposed least-squares fit of a power function to the data. Exponents of these curves are 2.16 for WDR cells and 3.49 for HT cells.
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Temperature FIG. 4. Effect of DLF cold block, ipsilateral to the recording site and contralateral to the cutaneous stimulation site, on responses of 8 thalamic cells to peripheral noxious temperature applied in receptive fields. Abscissa is the mean firing rate, and the ordinate is the temperature applied to the cutaneous receptive field. Points indicated by open boxes were obtained while the DLF was cooled with a probe temperature of 0°C. Control runs were done before the DLF was cooled.
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was generally a very sharp threshold for the WDR cells between 44 and 46°C whereas four of the ten HT units had higher thresholds (>46”C). The mean responses of the WDR and HT units, when plotted against the test temperatures, both followed a power function curve. The exponents of the two curves were different being 2.16 and 3.49, respectively, as determined by a least-squares fit of the data. The mean responses of the WDR units at 48OC and above were significantly greater than at 35OC (two-tailed t test, P < 0.01). The mean response at 46OC was not statistically different from the 35OC response, even though the 46OC response is 167% greater than the 35OC response. The mean responses of the HT units at stimulus temperatures of >48”C were significantly different (two-tailed t test, P < 0.05) from the mean response at 35OC. A point-by-point comparison of the two curves reveals that there is no difference (two-tailed t test, P > 0.05) between the mean responses of the WDR units compared with the mean responses of the HT units at all temperatures from 35 to 52OC (the tested temperature range), even though at temperatures >48OC the HT units had a consistently higher mean response. Efects of transmission block in the VQ and DLF Thirty-two of the nociceptive (WDR and HT) units were tested for the effects of blocking transmission through the VQ or DLF, ipsilateral to the recording site and contralatera1 to the cutaneous stimulation site, with the use of the cold-probe technique. The remaining three were tested with microsurgical lesions. Two cells were tested with both techniques. Cooling the DLF, ipsilateral to the recording site and contralateral to the cutaneous stimulation site, with a probe temperature of O°C resulted in a decreased responsiveness of 9 of the 35 nociceptive units to noxious thermal cutaneous stimulation. The responses of eight of these are shown in Fig. 4. The effects of DLF cooling on the response patterns of these nine units to thermal stimulation was variable. In all nine cases the responses at the higher stimulus temperatures (48°C and above) were less during the DLF cooling. The responses to the lower skin temperatures (~48°C) were increased in three units and decreased in three units. Four of the units demonstrated complete loss of any response to raising the skin temperature during DLF cooling. Two other units had their responses to noxious thermal skin stimulation increased by DLF cooling (Fig. 5). The majority of the units that demonstrated decreased responsiveness during either VQ or DLF block were located in the midportion of anterior-posterior extent of VPL (Fig. 1). The numbers are too small for statistical comparison. Four units demonstrated a decrease in responsiveness to skin heating during VQ cooling, ipsilateral to the recording site and contralateral to the cutaneous stimulation site, and one unit demonstrated an increased response to skin heating during VQ cooling (Fig. 5). One of the units with a decreased response during VQ cooling demonstrated a marked increased responsiveness during the DLF cooling (Fig. 5, top). VQ cooling affected the responsiveness of two units responding to noxious pinch but not to thermal skin stimulation. VQ cooling increased the responsiveness of one of these units and decreased the responsiveness of the
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Temperature FIG. 5. Four examples of varied effects of VQ cold block, ipsilateral to the recording site and contralateral to the cutaneous stimulation site, on responses of thalamic cells to noxious cutaneous thermal stimulation. Top plot also illustrates a cell with increased response during DLF cooling. Second plot shows a decreased response during VQ cooling. Third plot illustrates a change in baseline firing rate, whereas the bottom plot demonstrates an increased response during VQ cooling.
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Example of effects of microsurFIG. 6. gical lesions of the midthoracic spinal white matter on responses of a thalamic cell to peripheral noxious thermal stimulation. Left column contains peristimulus histograms of unit responses. Bin width is 1.1 s. Curve under each histogram is a plot of the temperature of the Peltier thermode in contact with the skin in the receptive field. Recordings B-E were done 5 min after the lesion indicated in the right column was made. Titles of histograms B-E refer to the placement of lesions. The “i” and “c” in headings of histograms refer to the ipsilatera1 or contralateral side of the lesion with respect to the thalamic recording site. Right column contains schematic cord sections illustrating the extent of sequential microsurgical lesions. Cell response to noxious thermal stimulation is abolished only with a contralateral dorsal column lesion (E).
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other. None of the units that showed a decreased responsiveness during VQ block also showed a decreased responsiveness during DLF block, and none of the units that showed a decreased responsiveness during DLF block also showed a decreased responsiveness during VQ block. Four of 25 WDR cells showed a decreased response to noxious stimuli during DLF cooling, ipsilateral to the recording site and contralateral to the cutaneous stimulation site, whereas five of ten HT units showed a decreased response to skin heating during DLF cooling. The greater proportion of HT cells being affected by DLF cooling is statistically significant (x* test with Yates correction for small numbers, P < 0.05). Of the 24 WDR cells tested, two had decreased responses to noxious stimuli during VQ cooling, whereas two of the eight HT cells tested had a decreased response to noxious peripheral stimulation during VQ cooling. These numbers are too small for statistical comparison. Four WDR units were tested during innocuous skin stimulation. The responses of three of the units to innocuous and noxious stimulation of the skin were not altered by either VQ or DLF cooling, ipsilateral to the recording site and contralateral to the cutaneous stimulation site. The responses of the fourth unit to innocuous skin displacement were increased during both VQ and DLF cooling. This unit’s responses to noxious skin heating were unaffected by DLF cooling but were increased by VQ cooling. Seven cells (2 HT, 5 WDR) were tested with microsurgical lesions. Three of these units were first studied with the cold-block technique and demonstrated no effect of VQ or DLF cooling, ipsilateral to the recording site and contralatera1to the cutaneous stimulation site, on their responses to thermal skin stimulation. Two of these units did not change their responses to noxious skin stimulation after complete hemisection of the spinal cord ipsilateral to the recording site, but they had their responses to noxious skin stimulation completely abolished by section of the dorsal column contralateral to the recording site (Fig. 6). Three nociceptive units were tested with spinal lesions only. One, responsive to pinch but not skin heating, showed an increase in spontaneous activity after a DLF lesion and then a loss of pinch response after VQ lesion ipsilateral to the recording site. One of these cells showed no effect to ipsilatera1 hemisection but had a greatly decreased response to noxious skin heating after a contralateral DLF lesion. Another cell had its response to noxious skin heating decreased by a contralateral DLF lesion and its response completely eliminated by an ipsilateral DLF lesion. The last cell in the group tested with microsurgical lesions was an LT cell that was unaffected by cooling the DLF or the VQ ipsilateral to the recording site, but its response was abolished by a contralateral DLF lesion. There was no effect of VQ or DLF cooling, ipsilateral to the recording site and contralateral to the cutaneous stimulation site, on the responsiveness of LT units.
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1985; KnifIki and Vahle-Hinz 1987)]. This segregation of nociceptive cells along the lateral and ventral border of the VBX in cat is similar to that described in previous studies (Honda et al. 1983; KnifIki and Craig 1985; Kniflki and Mizumura 1983; KnifIki and Vahle-Hinz 1987; Yokota et al. 1985, 1986, 1987, 1988). There was no discernable anatomic separation of HT and WDR nociceptive cells, a finding similar to other studies (Kniffki and Craig 1985; KnifIki and Mizumura 1983; KnifIki and Vahle-Hinz 1987). This may be due to our small sample size as Yokota (Yokota et al. 1987, 1988), evaluating large numbers of cells, noted a separation of these cell types in cat. The response characteristics of the thalamic cells to the DLF and the VQ cold blocks were also independent of their location in the periphery of VPL. This is consistent with anatomic studies indicating that the DSTT and the VSTT project to similar areas of the VBX in cat (Apkarian et al. 1987) and to similar areas of VPL in primate (Apkarian and Hodge 19894). The receptive fields of the LT cells are smaller than those of the HT and WDR cells. The HT cell receptive fields are minimally smaller than the WDR cell receptive fields, but are significantly larger than those reported by Yokota (Yokota et al. 1987, 1988). The difference between the receptive-field sizes of HT and WDR cells may be a reflection of organization of the spinal cord, because HT lamina I cells have receptive fields smaller than those of WDR cells that are found in deeper spinal laminae (Besson and Chaouch 1987; Ferrington et al. 1987; Gonatas et al. 1979; Price and Dubner 1977; Price and Mayer 1974; Wall 1967; Willis 1987). The receptive fields of the VPL periphery neurons were unilateral except for 2 of the 43 cells studied, whereas both cells located in POm had bilateral receptive fields. The lower-extremity receptive fields of nociceptive units were found in the lateral periphery of VPL and were consistent with the precise medial-lateral nonnociceptive somatotopy of the core of VPL (Berkley 1973; Guilbaud et al. 1977; Harris 1978); Honda et al. 1983; Kniflki and Craig 1985; KnifIki and Mizumura 1983). The thresholds of most of the thermal-responsive nociceptive cells fell within a narrow range of 44-46OC. However, some of the HT cells had thresholds >46OC. The thermal-responsive nociceptive cells were able to code for stimulus intensity by increasing response frequency at higher cutaneous stimulus temperatures. These properties of VPL periphery nociceptive cells are similar to those described in previous reports (Kenshalo et al. 1979; Peschanski et al. 1980). Most nociceptive responsive units responded to both thermal and noxious cutaneous stimuli in agreement with the work of Mitchell and Hellon (1977). Psychophysical studies have demonstrated that thermal sensitivity, as well as other sensations, follow a power function law (Stevens and Stevens 1962). The mean response curve of the WDR cells in this study follow a power function with an exponent of 2.16. A review by Harkins et al. (1986) cited studies showing pain-intensity estimations DISCUSSION with exponents between 2.03 and 2.68. Price et al. (1983) measured affective magnitude (a measure of unpleasantThe nociceptive thalamic cells described in this report were found primarily in the periphery of VPL [an area ness as opposed to intensity) in both chronic pain patients termed VBvp by Kniffki and coworkers (Kniffki and Craig and normal controls, and their mean responses fit a power
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function curve with an exponent of 3.8. This number is very similar to the exponent of the curve for our HT cells, 3.49. STT cells have also been described the physiological response curve of which is similar to the psychophysical curves just mentioned. Kenshalo et al. (1979) described nociceptive STT neurons the mean response of which to noxious temperature pulses of 30 s followed a power function with an exponent of 2.1. Though the variability of the individual cell responses are great, the similarity of these curves to previously described psychophysical power function curves is of interest and suggests roles for WDR and HT thalamic neurons in the sensory discriminative and affective aspects of nociception, respectively. These data are consistent with the idea that progressively greater stimulus temperatures recruit progressively more lateral thalamic cells (Mitchell and Hellon 1977). The effects of the cold-probe blocks on the response characteristics of the thalamic units were varied. With the ipsilateral (to the thalamic recording site) DLF block, there were nine nociceptive cells, of 35 that were tested, that showed a decreased level of response with thermal stimulation at 48OC or above. This suggests that thalamic units receive information about peripheral noxious stimuli through ipsilateral DLF. During DLF cooling, the responses of three of these cells at cutaneous stimulus temperatures ~48°C were decreased, whereas three cells had an increased response. This latter effect is probably related to the interruption of descending inhibition (Basbaum and Fields 1978), a mechanism likely responsible for the characteristics of the two units that showed an increased response to DLF block at all test temperatures. One of the striking findings in this study was the lack of a more pronounced facilitator-y effect on thalamic neurons of blocking descending inhibition through the DLF, given the role of the DLF in descending inhibition of spinal nociceptive responses (Basbaum and Fields 1978; Beall et al. 1976). The effects of the DLF cooling, ipsilateral to the recording site and contralateral to the cutaneous stimulation site, most likely reflect alterations in transmission through the DSTT or indirect lamina I cell inputs (Hylden et al. 1986; McMahon and Wall 1983, 1988; Yezierski et al. 1987) to the thalamus via the dorsolateral pons or mesencephalon, because the other major ascending pathway in the DLF is the spinocervical tract, which is destined to affect the contralatera1 thalamus. It is impossible with the techniques used in this study to differentiate direct DSTT effects from those resulting from indirect lamina I cell input to the thalamus. Similarly, the effects of VQ cooling likely reflect decreased transmission through both the VSTT and the indirect ventral pathways to the thalamus. Although the results presented here clearly demonstrate that information concerning peripheral noxious stimulation may ascend in both the VQ and the DLF ipsilateral to the recording site and contralateral to the cutaneous stimulation site, the majority of nociceptive thalamic cells was not affected by either block. A major reason for this is probably related to the biophysical properties of the cold probe and the white matter. Franz and Iggo (1968) have shown in peripheral nerves that nonmyelinated fibers are less sensitive to cooling and stop conducting at lower tem-
NOCICEPTION
1409
peratures than myelinated fibers. The temperature increases in the spinal cord as one moves away from the probe (Apkarian et al. 1989). Therefore the effective area of block is smaller for nonmyelinated fibers than for myelinated fibers. Lamina I cell axons have been shown to ascend in the DLF (Apkarian and Hodge 1989a,c; Jones et al. 1985, 1987; McMahon and Wall 1983; Stevens et al. 1989) and are concentrated in the periphery of this funiculus in rat (McMahon and Wall 1983). Lamina I cell axons are thin and finely myelinated or unmyelinated (Craig and Kniflki 1985b; Ferrington et al. 1987). It is therefore reasonable to expect that the axons in the DLF that subserve nociception would be effected by the cold blocks. The white-matter area of the VQ is larger than that of the DLF, and it would be expected that more axons traveling in this quadrant would escape the effects of the cold blocks. This is consistent with the results found in this study. Not all the nociceptive thalamic units received their input through the ipsilateral spinal tracts, that is, contralatera1 to the receptive fields. Two nociceptive cells were tested with ipsilateral VQ and DLF cold blocks and microsurgical hemisection with no effect. Their responses were eliminated by sectioning the dorsal column contralateral to the recording site. Another cell response was maintained with ipsilateral hemisection and abolished by sectioning of the contralateral DLF, implicating the spinocervical tract as the pathway of nociceptive input. These results are consistent with the known potential responses of dorsal column nuclei and lateral cervical nucleus neurons to noxious cutaneous stimuli and indicated that the effects of cooling did not spread to the contralateral dorsal column or DLF (Giesler et al. 1979; Willis et al. 1986). The cells that showed a decreased response to DLF block represented 50% of the HT cells (5/ 10) and 16% of the WDR cells (4/25). The lamina I cells projecting to the contralateral thalamus are primarily HT nociceptive and thermoreceptive neurons (Craig and Kniffki 1985b) as are the spinomesencephalic lamina I cells ascending in the DLF (Hylden et al. 1986; Swett et al. 1985). This implies that lamina I cells preferentially influence the HT cells in lateral thalamus and is consistent with the important role of the DLF in processing of noxious peripheral stimuli in cat (Casey and Morrow 1988; Kennard 1954). The lack of any thalamic. neurons with nociceptive responses decreased by both VQ and DLF cooling suggestsa functional segregation at the thalamic level of spinal WDR and HT input. These data, then, represent the only study of cat thalamic neuronal responses to noxious thermal stimuli and indicate that information transmitted rostrally through the DLF ipsilateral to the thalamic recording site contributes to thalamic neuronal responses to cutaneous noxious stimulation. It is impossible with this paradigm to determine the relative contributions to thalamic nociception of the direct DSTT compared with potential indirect thalamic input through spinopontothalamic and spinomesencephalic-thalamic pathways both of which have been described (Blomqvist and Berkley 1987; Bowsher et al. 1968; Comans and Snow 198 1; Hylden et al. 1986; Peschanski and Besson 1984; Yezierski et al. 1987). The important point is that the standard assumption that nociceptive in-
1410
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formation reaches the thalamus through the classical VQ, STT, and spinoreticular pathways is an oversimplification and that the DSTT, made up of axons of lamina I STT neurons ascending in the DLF, likely plays a significant role in thalamic nociception in cat. thank N. Horton for expert technical assistance. This work was supported in part by National Institute of Neurological Disorders and Stroke Grant RO 1-NS2289 1 and by a gift from the Perkins foundation. Address for reprint requests: C. Hodge, Dept. of Neurosurgery, State University of New York, Health Science Center, Syracuse, 750 East Adams St., Syracuse, NY 132 10. We
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