Itch elicited by intradermal injection of serotonin, intracisternal injection of morphine, and their synergistic interactions in rats.

We used the cheek model of itch and pain in rats to determine the dose-response relationships for intradermal injection of serotonin and α methylserotonin on scratching behavior. We also determined the dose-related effects of intracisternally injected morphine on scratching, effects that were greatly reduced by administration of the opiate antagonist naloxone. We then examined the interactions of intradermal injection of serotonin and intracisternal injection of morphine on scratching and found that the two procedures act synergistically to increase itch. These results suggest that morphine applied to the CNS is capable of producing itch and greatly increasing itch originating in the skin (hyperknesis).

Identification of dorsal root ganglion neurons that innervate the common bile duct of rats.

Pain originating in the bile duct is common and many patients who have suffered from it report that it is one of the most intense forms of pain that they have experienced. Many uncertainties remain about the mechanisms underlying pain originating in the bile duct. For example, the dorsal root ganglion (DRG) neurons that give rise to the sensory innervation of the common bile duct (CBD) have not been identified and examined in any species. The goal of the present study was to determine the number, distribution, and size of DRG neurons that innervate the CBD in rats. Injections of WGA-HRP or CTB-HRP were restricted to the lumen of the bile duct. Injections of WGA-HRP labeled a mean number of about 500 DRG neurons bilaterally throughout all thoracic and upper lumbar levels. Injections of CTB-HRP labeled smaller numbers of DRG neurons. Application of colchicine onto the surface of the CBD reduced the number of cells labeled following injections of WGA-HRP into the lumen of the CBD by roughly 86%, suggesting that tracer had not spread in large amounts out of the CBD and labeled afferent fibers in other tissues. Approximately 85% of the neurons labeled with WGA-HRP had cell bodies that were classified as small; the remainder were medium in size. Injections of CTB-HRP labeled cell bodies of varying sizes, including a few large diameter cell bodies. These results indicate that a large number of primarily small DRG cells, located bilaterally at many segmental levels, provide a rich innervation of the common bile duct.

Projections from the marginal zone and deep dorsal horn to the ventrobasal nuclei of the primate thalamus.

It has been concluded recently that if a projection from the marginal zone to the ventral posterior lateral (VPL) nucleus exists, it is sparse. Given the importance of the marginal zone in nociception, this conclusion has raised doubts about the significance of the role of the ventrobasal complex in nociception. We have reexamined this projection using injections of the retrograde tracer, cholera toxin subunit B, into one side of the lateral thalamus in macaque monkeys. The injections were confined to the ventrobasal complex (with minimal spread to adjacent nuclei that do not receive spinal projections) in two animals. Many retrogradely labeled neurons were found in lamina I (as well as in lamina V) of the contralateral spinal and medullary dorsal horn. The results are consistent with the view that neurons in the marginal zone contribute prominently to the spinothalamic and trigeminothalamic projections to the VPL and ventral posterior medial (VPM) nuclei. This pathway is likely to be important for the sensory-discriminative processing of nociceptive information with respect to the location and intensity of painful stimuli.

Position of spinothalamic tract axons in upper cervical spinal cord of monkeys.

Percutaneous upper cervical cordotomy continues to be performed on patients suffering from several types of severe chronic pain. It is believed that the operation is effective because it cuts the spinothalamic tract (STT), a primary pathway carrying nociceptive information from the spinal cord to the brain in humans. In recent years, there has been controversy regarding the location of STT axons within the spinal cord. The aim of this study was to determine the locations of STT axons within the spinal cord white matter of C2 segment in monkeys using methods of antidromic activation. Twenty lumbar STT cells were isolated. Eleven were classified as wide dynamic range neurons, six as high-threshold cells, and three as low-threshold cells. Eleven STT neurons were recorded in the deep dorsal horn and nine in superficial dorsal horn. The axons of the examined neurons were located at antidromic low-threshold points (<30 microA) within the contralateral lateral funiculus of C2. All low-threshold points were located ventral to the denticulate ligament, within the lateral half of the ventral lateral funiculus (VLF). None were found in the dorsal half of the lateral funiculus. The present findings support our previous suggestion that STT axons migrate ventrally as they ascend the length of the spinal cord. Also, the present findings indicate that surgical cordotomies that interrupt the VLF in C2 likely disrupt the entire lumbar STT.

Locations of spinothalamic tract axons in cervical and thoracic spinal cord white matter in monkeys.

The spinothalamic tract (STT) is the primary pathway carrying nociceptive information from the spinal cord to the brain in humans. The aim of this study was to understand better the organization of STT axons within the spinal cord white matter of monkeys. The location of STT axons was determined using method of antidromic activation. Twenty-six lumbar STT cells were isolated. Nineteen were classified as wide dynamic range neurons and seven as high-threshold cells. Fifteen STT neurons were recorded in the deep dorsal horn (DDH) and 11 in superficial dorsal horn (SDH). The axons of 26 STT neurons were located at 73 low-threshold points (<30 microA) within the lateral funiculus from T(9) to C(6). STT neurons in the SDH were activated from 33 low-threshold points, neurons in the DDH from 40 low-threshold points. In lower thoracic segments, SDH neurons were antidromically activated from low-threshold points at the dorsal-ventral level of the denticulate ligament. Neurons in the DDH were activated from points located slightly ventral, within the ventral lateral funiculus. At higher segmental levels, axons from SDH neurons continued in a position dorsal to those of neurons in the DDH. However, axons from neurons in both areas of the gray matter were activated from points located in more ventral positions within the lateral funiculus. Unlike the suggestions in several previous reports, the present findings indicate that STT axons originating in the lumbar cord shift into increasingly ventral positions as they ascend the length of the spinal cord.

Physiological studies of spinohypothalamic tract neurons in the lumbar enlargement of monkeys.

Recent anatomic results indicate that a large direct projection from the spinal cord to the hypothalamus exists in monkeys. The aim of this study was to determine whether the existence of this projection could be confirmed unambiguously using electrophysiological methods and, if so, to determine the response characteristics of primate spinohypothalamic tract (SHT) neurons. Fifteen neurons in the lumbar enlargement of macaque monkeys were antidromically activated using low-amplitude current pulses in the contralateral hypothalamus. The points at which antidromic activation thresholds were lowest were found in the supraoptic decussation (n = 13) or in the medial hypothalamus (n = 2). Recording points were located in the superficial dorsal horn (n = 1), deep dorsal horn (n = 10), and intermediate zone (n = 4). Each of the 12 examined neurons had cutaneous receptive fields on the ipsilateral hindlimb. All neurons responded exclusively or preferentially to noxious stimuli, suggesting that the transmission of nociceptive information is an important role of primate SHT axons. Twelve SHT neurons were also antidromically activated from the thalamus. In all cases, the antidromic latency from the thalamus was shorter than that from the hypothalamus, suggesting that the axons pass through the thalamus then enter the hypothalamus. These results confirm the existence of a SHT in primates and suggest that this projection may contribute to the production of autonomic, neuroendocrine, and emotional responses to noxious stimuli in primates, possibly including humans.

A method for improving the accuracy of stereotaxic procedures in monkeys using implanted fiducial markers in CT scans that also serve as anchor points in a stereotaxic frame.

We developed a relatively inexpensive method for stereotaxic placement of electrodes or needles in the brains of monkeys. Steel balls were affixed to the skulls of monkeys. These balls served as fiducial markers and were also used as points at which the monkey's skull was held in a modified stereotaxic apparatus. Computed tomography (CT) was used to establish the location of an injection target with respect to the fiducial markers. A computer program related the CT coordinates to stereotaxic coordinates. These were used to direct an electrode marker toward a target in the hypothalamus. With the marker left in place, the monkey was removed from the stereotaxic frame and a second CT scan was performed. Corrections for errors in marker placement were made and retrograde tracers were injected. This procedure was found to be more accurate and reliable than conventional stereotaxic procedures. The accuracy and repeatability of the technique were also established using a phantom model of a monkey's skull. Two important advantages of this method are that animals can be repeatedly placed into the stereotaxic frame in precisely the same position and that there are many opportunities during the procedure to check for and correct errors.

Spinohypothalamic tract neurons in the cervical enlargement of rats: locations of antidromically identified ascending axons and their collateral branches in the contralateral brain.

Antidromic activation was used to determine the locations of ascending spinohypothalamic tract (SHT) axons and their collateral projections within C1, medulla, pons, midbrain, and caudal thalamus. Sixty-four neurons in the cervical enlargement were antidromically activated initially by stimulation within the contralateral hypothalamus. All but one of the examined SHT neurons responded either preferentially or specifically to noxious mechanical stimuli. A total of 239 low-threshold points was classified as originating from 64 ascending (or parent) SHT axons. Within C1, 38 ascending SHT axons were antidromically activated. These were located primarily in the dorsal half of the lateral funiculus. Within the medulla, the 29 examined ascending SHT axons were located ventrolaterally, within or adjacent to the lateral reticular nucleus or nucleus ambiguus. Within the pons, the 25 examined ascending SHT axons were located primarily surrounding the facial nucleus and the superior olivary complex. Within the caudal midbrain, the 23 examined SHT ascending axons coursed dorsally in a position adjacent to the lateral lemniscus. Within the anterior midbrain, SHT axons traveled rostrally near the brachium of the inferior colliculus. Within the posterior thalamus, all 17 examined SHT axons coursed rostrally through the posterior nucleus of thalamus. A total of 114 low-threshold points was classified as collateral branch points. Sixteen collateral branches were seen in C1; these were located primarily int he deep dorsal horn. Forty-five collateral branches were located in the medulla. These were primarily in or near the medullary reticular nucleus, nucleus ambiguus, lateral reticular nucleus, parvocellular reticular nucleus, gigantocellular reticular nucleus, cuneate nucleus, and the nucleus of the solitary tract. Twentysix collateral branches from SHT axons were located in the pons. These were in the pontine reticular nucleus caudalis, gigantocellular reticular nucleus, parvocellular reticular nucleus, and superior olivary complex. Twenty-three collateral branches were located in the midbrain. These were in or near the mesencephalic reticular nucleus, brachium of the inferior colliculus, cuneiform nucleus, superior colliculus, central gray, and substantia nigra. Int he caudal thalamus, two branches were in the posterior thalamic nucleus and two were in the medial geniculate. These results indicate that SHT axons ascend toward the hypothalamus in a clearly circumscribed projection in the lateral brain stem and posterior thalamus. In addition, large numbers of collaterals from SHT axons appears to project to a variety of targets in C1, the medulla, pons, midbrain, and caudal thalamus. Through its widespread collateral projections, the SHT appears to be capable of providing nociceptive input to many areas that are involved in the production of multifaceted responses to noxious stimuli.

Spinothalamic and spinohypothalamic tract neurons in the sacral spinal cord of rats. I. Locations of antidromically identified axons in the cervical cord and diencephalon.

1. A goal of this study was to determine the sites in the diencephalon to which neurons in sacral spinal segments of rats project. Therefore, 95 neurons were recorded extracellularly in spinal segments L6-S2 of rats that were anesthetized with urethan. These neurons were activated initially antidromically with currents < or = 30 microA from a monopolar stimulating electrode placed into the contralateral posterior diencephalon. The mean +/- SE current for antidromic activation from these sites was 16 +/- 0.8 microA. These neurons were recorded in the superficial dorsal horn (4%), deep dorsal horn (89%), and intermediate zone and ventral horn (4%). 2. Systematic antidromic mapping techniques were used to map the axonal projections of 41 of these neurons within the diencephalon. Thirty-three neurons (80%) could be activated antidromically with currents < or = 30 microA only from points in the contralateral thalamus and are referred to as spinothalamic tract (STT) neurons. Eight neurons (20%) were activated antidromically with low currents from points in both the contralateral thalamus and hypothalamus, and these neurons are referred to as spinothalamic tract/ spinohypothalamic tract (STT/SHT) neurons. Three additional neurons were activated antidromically with currents < or = 30 microA only from points within the contralateral hypothalamus and are referred to as spinohypothalamic tract (SHT) neurons. The diencephalic projections of another 51 neurons were mapped incompletely. These neurons are referred to as spinothalamic/unknown (STT/ U) neurons to indicate that it was not known whether their axons ascended beyond the site in the thalamus from which they initially were activated antidromically. 3. For 31 STT neurons, the most anterior point at which antidromic activation was achieved with currents < or = 30 microA was determined. Fourteen (45%) were activated antidromically only from sites posterior to the ventrobasal complex (VbC) of the thalamus. Sixteen STT neurons (52%) were activated antidromically with low currents from sites at the level of the VbC, but not from more anterior levels. One STT neuron (3%) was activated antidromically from the anteroventral nucleus of the thalamus. 4. STT/SHT neurons were antidromically activated with currents < or = 30 microA from the medial lemniscus (ML), anterior pretectal nucleus (APt), posterior nuclear group and medial geniculate nucleus (Po/MG), and zona incerta in the thalamus and from the optic tract (OT), supraoptic decussation, or lateral area of the hypothalamus. No differences in the sites in the thalamus from which STT and STT/SHT neurons were activated antidromically were apparent. Five STT/SHT neurons (62%) were activated antidromically from points in the thalamus in the posterior diencephalon and from points in the hypothalamus at more anterior levels. Three STT/SHT neurons (38%) were activated antidromically with currents < or = 30 microA from sites in both the thalamus and hypothalamus at the same anterior-posterior level of the diencephalon. All three of these STT/SHT neurons projected to the intralaminar nuclei (parafascicular or central lateral nuclei) of the thalamus. 5. Seven STT/SHT neurons were tested for additional projections to the ipsilateral brain. Two (29%) were activated antidromically with currents < or = 30 microA and at longer latencies from sites in the ipsilateral diencephalon. One could only be activated antidromically from the hypothalamus ipsilaterally. The other was activated antidromically at progressively increasing latencies from points in the ipsilateral brain that extended as far posteriorly as the posterior pole of the MG. 6. Fifty-eight STT, STT/SHT, and STT/U neurons were classified as low-threshold (LT), wide dynamic range (WDR), or highthreshold (HT) neurons based on their responsiveness to innocuous and noxious mechanical stimuli applied to their cutaneous receptive fields.(ABSTRACT TRUNCATED)

Spinothalamic and spinohypothalamic tract neurons in the sacral spinal cord of rats. II. Responses to cutaneous and visceral stimuli.

1. A goal of this study was to determine whether neurons in the sacral spinal cord that project to the diencephalon are involved in the processing and transmission of sensory information that arises in the perineum and pelvis. Therefore, 58 neurons in segments L6-S2 were activated antidromically with currents < or = 30 microA from points in the contralateral diencephalon in rats that were anesthetized with urethan. 2. Responses to mechanical stimuli applied to the cutaneous receptive fields of these neurons were used to classify them as low-threshold (LT), wide dynamic range (WDR) or high-threshold (HT) neurons. Twenty-two neurons (38%) responded preferentially to brushing (LT neurons). Eighteen neurons (31%) responded to brushing but responded with higher firing frequencies to noxious mechanical stimuli (WDR neurons). Eighteen neurons (31%) responded only to noxious intensities of mechanical stimulation (HT neurons). LT neurons were recorded predominantly in nucleus proprius of the dorsal horn. Nociceptive neurons (WDR and HT) were recorded throughout the dorsal horn. 3. Cutaneous receptive fields were mapped for 56 neurons. Forty-five (80%) had receptive fields that included at least two of the following regions ipsilaterally: the rump, perineum, or tail. Eleven neurons (20%) had receptive fields that were restricted to one of these areas or to the ipsilateral hind limb. Thirty-eight neurons (68%) had cutaneous receptive fields that also included regions of the contralateral tail or perineum. On the perineum, receptive fields usually encompassed perianal and perivaginal areas including the clitoral sheath. There were no statistically significant differences in the locations or sizes of receptive fields for LT neurons compared with nociceptive (WDR and HT) neurons. 4. Thirty-seven LT, WDR, and HT neurons were tested for their responsiveness to heat stimuli. Five (14%) responded to increasing intensities of heat with graded increases in their firing frequencies. Thirty-two LT, WDR, and HT neurons also were tested with cold stimuli. None responded with graded increases in their firing frequencies to increasingly colder stimuli. There were no statistically significant differences among the responses of LT, WDR, and HT neurons to either heat or cold stimuli. 5. Forty LT, WDR, and HT neurons were tested for their responsiveness to visceral stimuli by distending a balloon placed into the rectum and colon with a series of increasing pressures. Seventeen (43%) exhibited graded increases in their firing frequencies in response to increasing pressures of colorectal distention (CrD). None of the responsive neurons responded reproducibly to CrD at an intensity of 20 mmHg, and all responded at intensities of > or = 80 mmHg. More than 90% responded abruptly at stimulus onset, responded continuously throughout the stimulus period, and stopped responding immediately after termination of the stimulus. 6. Thirty-one neurons were tested for their responsiveness to distention of a balloon placed inside the vagina. Eleven (35%) exhibited graded increases in their firing frequencies in response to increasing pressures of vaginal distention (VaD). The thresholds and temporal profiles of the responses to VaD were similar to those for CrD. Twenty-nine neurons were tested with both CrD and VaD. Thirteen (45%) were excited by both stimuli, four (14%) responded to CrD but not VaD, and one (3%) was excited by VaD but not CrD. Neurons excited by CrD, VaD, or both were recorded throughout the dorsal horn. 7. As a population, WDR neurons, but not LT or HT neurons, encoded increasing pressures of CrD and VaD with graded increases in their firing frequencies. The responses of WDR neurons to CrD differed significantly from those of either LT or HT neurons. Regression analyses of the stimulus-response functions of responsive WDR neurons to CrD and VaD were described by power functions with exponents of 1.6 and 2.4, respectively.(ABSTRACT TRUNCATED)

Spinohypothalamic tract neurons in the cervical enlargement of rats: descending axons in the ipsilateral brain.

Spinohypothalamic tract (SHT) cells are spinal cord neurons with axons that project directly to or through the contralateral hypothalamus. Frequently, SHT axons decussate in the posterior optic chiasm, turn posteriorly and descend to unknown locations in the ipsilateral brain. We attempted to determine the course and the termination of these descending axons. Sixty neurons in the cervical enlargement of rats were antidromically activated initially from the contralateral hypothalamus and then from multiple anterior-posterior levels in the ipsilateral brain. Fifty-three (88%) were backfired with low currents at increased latencies from the ipsilateral brain. The axons of 35 neurons were surrounded with electrode penetrations from which high currents could not activate the neuron antidromically, suggesting the examined axons terminated in the surrounded areas. Seven SHT axons that were surrounded (20%) appeared to terminate in the contralateral hypothalamus, 5 (14%) in the ipsilateral hypothalamus, and 9 (26%) in the ipsilateral thalamus. Fourteen SHT axons (40%) ended in the ipsilateral midbrain mainly in the superior colliculus, cuneiform nucleus or nucleus brachium inferior colliculus. An additional 11 axons were followed even further posteriorly into the ventral pons or rostral medulla. Each of the 26 neurons that could be physiologically classified responded either preferentially or specifically to noxious mechanical stimuli. These results indicate that SHT axons course through a surprisingly long and complex path. After decussating in the hypothalamus, the axons of many SHT neurons descend into the ipsilateral posterior thalamus, midbrain, pons, or even rostral medulla. These axons may provide nociceptive information to a variety of nuclei throughout the diencephalon and brainstem bilaterally.

Direct spinal pathways to the limbic system for nociceptive information.

The hypothalamus is believed to play important roles in several aspects of nociception. Previously, nociceptive information was thought to reach hypothalamic neurons through indirect, multisynaptic pathways. However, we have found that thousands of neurons throughout the length of the spinal cord in rats send axons directly into the hypothalamus, and many of these axons carry nociceptive information. The axons often follow a complex course, ascending through the contralateral spinal cord, brainstem, thalamus and hypothalamus. They then cross the midline and enter the ipsilateral hypothalamus, turn posteriorly, and continue into the ipsilateral thalamus. These axons might provide nociceptive information to a variety of nuclei in the thalamus and hypothalamus bilaterally.

Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. III. Locations of antidromically identified axons in the cervical cord white matter.

1. Fifty-five neurons in the cervical enlargement (C6-C8) of urethan-anesthetized rats were antidromically activated from the contralateral posterior diencephalon. In all cases, antidromic thresholds were < or = 30 microA. The locations of the axons of these neurons within the white matter of segments C2-C6 were determined by tracking systematically using a second antidromic stimulating electrode. 2. The recording locations of 51 neurons were marked and recovered. Twenty neurons were recorded in the superficial dorsal horn (SDH) and 31 were in the deep dorsal horn (DDH). Eighty-three lowest threshold points for antidromic activation within the white matter of segments C2-C6 were determined for these 51 neurons. The mean antidromic threshold at these points was 9.5 +/- 0.5 (SE) microA. For 26 neurons, the lowest threshold point for antidromic activation was determined at one segmental level. We also attempted to determine whether individual axons maintained their position as they ascended through the cervical cord white matter. In 25 cases, lowest threshold points were determined at two or more segmental levels. 3. In segments C5-C6, 88% (7/8) of the lowest threshold points of the examined axons were located in the contralateral ventral funiculus, indicating that the majority of examined axons crossed the midline within one or two segments. 4. In segments C3-C4, 32% (14/44) of all examined axons were found in the dorsal lateral funiculus (DLF) and 66% (29/44) were within the ventral quadrant [ventral lateral funiculus (VLF) and ventral funiculus (VF)]. Sixty-nine percent (11/16) of the axons of neurons recorded in the SDH were located in the contralateral DLF and 31% (5/16) were located in the ventral quadrant (VQ). In contrast, only 11% (3/28) of the axons of neurons recorded in the DDH were located in the contralateral DLF and 86% (24/28) were located in the VQ. Therefore, in segments C3-C4, the locations of axons differed significantly. Those from neurons recorded in the SDH were located primarily in the DLF and those from neurons recorded in the DDH were located principally in the VQ. 5. In segment C2, 74% (23/31) of all examined axons were found in the DLF, 23% (7/31) were in the VQ, and 3% (1/31) were in the dorsal horn. Thus, the percentage of all examined axons in the DLF in C2 was approximately 2.5 times greater than it was in C3-C4.(ABSTRACT TRUNCATED AT 400 WORDS)

Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. I. Locations of antidromically identified axons in the thalamus and hypothalamus.

1. Seventy-seven neurons in the cervical enlargement of rats anesthetized with urethan were initially antidromically activated using currents < or = 30 microA from the contralateral posterior thalamus. A goal of these experiments was to determine the course of physiologically characterized spinal axons within the diencephalon. Therefore, in 38 cases, additional antidromic mapping was done throughout the mediolateral extent of the diencephalon at multiple anterior-posterior planes. 2. Electrolytic lesions marking the recording sites were recovered for 71 neurons. Thirty-one were located in the superficial dorsal horn (SDH); 39 were in nucleus proprius or the lateral reticulated area of the deep dorsal horn (DDH), and one was in the ventral horn. 3. Eight of 38 (21%) neurons that were tested for more anterior projections could only be antidromically activated with currents < or = 30 microA from sites in the contralateral posterior thalamus. Such neurons are referred to as spinothalamic tract (STT) neurons. Lesions marking the lowest threshold points for antidromic activation were located in or near the posterior thalamic group (Po). At more anterior levels, considerably higher currents were required for antidromic activation or it was not possible to activate the neurons with currents up to 500 microA. Four of these neurons were physiologically characterized and each responded preferentially to noxious mechanical stimuli (wide dynamic range, WDR). Each of the three neurons that were tested responded to noxious heat stimuli. These findings confirm anatomic studies that have shown that a number of STT axons terminate in Po and suggest that such axons that originate in the cervical enlargement carry nociceptive input from the upper extremity. 4. In 15 cases, electrode penetrations were made systematically throughout much of the contralateral ventrobasal complex (VbC). In 17 cases, penetrations were made throughout the intralaminar nuclei contralaterally, including the central lateral nucleus (CL). Surprisingly, only one of the examined axons was antidromically activated with low currents from CL and one from VbC, although both of these nuclei are known to receive sizeable inputs from the STT. 5. Many of the axons (27 of the 38 tested, 71%) that were initially antidromically activated from the contralateral posterior thalamus could also be antidromically activated with low currents (< or = 30 microA) and at increased latencies from sites located anteriorly in the contralateral hypothalamus. Such neurons are referred to as spinothalamic tract/spinohypothalamic tract (STT/SHT) neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. II. Responses to innocuous and noxious mechanical and thermal stimuli.

1. The goal of this study was to gather data that would increase our understanding of nociceptive processing by spinothalamic tract (STT) neurons that receive inputs from the hand and arm. Fifty neurons in the cervical enlargement of urethan-anesthetized rats were antidromically activated from the contralateral posterior thalamus. A stimulating electrode was moved systematically within an anterior-posterior plane in the thalamus until a point was located where the smallest amount of current antidromically activated the neuron. The antidromic thresholds at each of these lowest threshold points was < or = 30 microA; the mean antidromic threshold was 15.4 +/- 1.0 (SE) microA. Lowest threshold points were found primarily in the posterior thalamic group (Po), zona incerta, and in or near the supraoptic decussation. 2. The recording sites of 47 neurons were marked and recovered. Recording sites were located in the superficial dorsal horn (SDH, n = 15), deep dorsal horn (DDH, n = 31), and ventral horn (n = 1). Recording sites were located across the mediolateral extent of the SDH. Within the DDH, recording sites were concentrated laterally in nucleus proprius and dorsally in the lateral reticulated area. The locations of the recording points confirm previous anatomic descriptions of STT neurons in the cervical enlargement. 3. Cutaneous excitatory receptive fields were restricted to the ipsilateral forepaw or forelimb in 67% (10/15) of the neurons recorded in the SDH and 42% (13/31) of the neurons recorded in the DDH. Neurons having larger, more complex receptive fields were also commonly encountered. Thirty-three percent (5/15) of the neurons recorded in the SDH and 58% (18/31) recorded in the DDH had receptive fields that were often discontinuous and included areas of the ipsilateral shoulder, thorax, and head, including the face. 4. Innocuous and noxious mechanical stimuli were applied to the receptive field of each neuron. Fifty percent (25/50) responded to innocuous mechanical stimuli but responded at higher frequencies to noxious stimuli (wide dynamic range, WDR). Forty-four percent (22/50) responded only to noxious stimuli (high threshold, HT). Six percent (3/50) responded preferentially to innocuous stimuli (low threshold, LT). WDR and HT neurons were recorded in both the SDH and DDH, including nucleus proprius, an area not typically associated with nociceptive transmission at other levels of the cord. Sixty percent (9/15) of the units recorded in the SDH were classified as WDR neurons; the other 40% (6/15) were classified HT. Forty-eight percent (15/31) of the units recorded in the DDH were classified as WDR neurons and 42% (13/31) as HT.(ABSTRACT TRUNCATED AT 400 WORDS)

Physiological characterization of spinohypothalamic tract neurons in the lumbar enlargement of rats.

1. Ninety-six neurons in the lumbar enlargement of urethananesthetized rats were antidromically activated from the contralateral hypothalamus. The antidromic stimulating electrode was moved systematically within the hypothalamus until antidromic activation could be produced with currents of less than or equal to 50 microA (18.6 +/- 10.8 microA; mean +/- SD). The points at which antidromic activation thresholds were lowest were found in several regions of the hypothalamus but were concentrated in the optic tract and the supraoptic decussation. 2. The recording locations of 79 spinohypothalamic tract (SHT) neurons were marked and recovered. Twenty-nine were located in the superficial dorsal horn (SDH), 42 in the deep dorsal horn (DDH), 4 in the intermediate zone, and 2 in the gray matter surrounding the central canal. Two additional marks were located in the dorsal lateral funiculus (DLF). 3. The responses of 46 SHT neurons were examined during innocuous and noxious mechanical stimulation of their receptive fields. Forty-eight percent of recorded SHT neurons responded to both innocuous and noxious stimuli (wide dynamic range, WDR) and 39% responded only to noxious stimuli (high threshold, HT). Therefore 87% of SHT neurons responded preferentially or exclusively to noxious mechanical stimulation. Nine percent of SHT neurons responded exclusively to innocuous manipulation of joints and muscles. Four percent of SHT neurons responded only to innocuous tactile stimul (low threshold, LT). WDR, HT, and LT neurons were recorded widely throughout the dorsal horn; no relationship was found between the locations of recording sites in the dorsal horn and the response types of the neurons. SHT neurons that responded to stimulation of muscle, tendon, or joint were recorded deep in the gray matter. 4. The effects of heating the receptive fields were determined for 25 SHT neurons. Fourteen (56%) responded to thermal stimuli. Six (43%) of the responsive neurons responded at low frequencies to innocuous warming (38-41 degrees C) but more vigorously to noxious (greater than or equal to 45 degrees C) heating. The other eight responded only to noxious heat. Eighteen percent (3/17) of tested SHT neurons were activated by noxious cooling of their receptive fields. 5. Cutaneous receptive fields of most recorded SHT neurons were small, typically involving areas as small as two or three toes on the ipsilateral hindlimb; the largest receptive fields covered the entire paw. These findings indicate that relatively precise information about the location of innocuous and noxious stimuli is conveyed directly to the hypothalamus by SHT neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Distributions of spinothalamic, spinohypothalamic, and spinotelencephalic fibers revealed by anterograde transport of PHA-L in rats.

Fibers projecting from several levels of the spinal cord to the diencephalon and telencephalon were labeled anterogradely with Phaseolus vulgaris leucoagglutinin injected iontophoretically. Labeled fibers in the thalamus confirmed projections previously observed. In addition, many labeled fibers were seen in the hypothalamus and in telencephalic areas not generally recognized previously as receiving such projections. In the hypothalamus, these areas included the lateral hypothalamus (including the medial forebrain bundle), the posterior hypothalamic area, the dorsal hypothalamic area, the dorsomedial nucleus, the paraventricular nucleus, the periventricular area, the suprachiasmatic nucleus, and the lateral and medial preoptic areas. In the telencephalon, areas with labeled fibers included the ventral pallidum, the globus pallidus, the substantia innominata, the basal nucleus of Meynert, the amygdala (central nucleus), the horizontal and vertical limbs of the diagonal band of Broca, the medial and lateral septal nuclei, the bed nucleus of the stria terminalis, the nucleus accumbens, infralimbic cortex, and medial orbital cortex. These results suggest that somatosensory, possibly including visceral sensory, information is carried directly from the spinal cord to areas in the brain involved in autonomic regulation, motivation, emotion, attention, arousal, learning, memory, and sensory-motor integration. Many of these areas are associated with the limbic system.

The cells of origin of the spinohypothalamic tract in cats.

Various cutaneous and visceral stimuli alter the discharge rates of neurons in the hypothalamus. Changes in the activity of hypothalamic neurons are thought to play important roles in eliciting neuroendocrine, autonomic, and affective responses to somatosensory and visceral stimuli. Information from peripheral structures has been considered generally to reach the hypothalamus via multisynaptic ascending pathways. Recently, a direct projection from the spinal cord to the hypothalamus was demonstrated in rats. The goal of this study was to determine whether a similar projection exists in cats. Either wheat germ agglutinin conjugated to horseradish peroxidase, a mixture of this tracer and the B subunit of cholera toxin conjugated to horseradish peroxidase, or fast blue was injected into the hypothalamus of cats. Injections were centered in the hypothalamus in seven cats and did not spread to the thalamus, zona incerta or midbrain. After these injections, retrogradely labeled neurons were observed bilaterally in each of the 17 spinal segments that were examined. A total of approximately 400-500 labeled neurons was observed in alternate sections through these segments in the most effective cases. Roughly 70% of the labeled neurons were located contralaterally. Labeled neurons were found predominantly in the deep dorsal horn, the intermediate zone/ventral horn and in the area surrounding the central canal. A few were also noted in the superficial dorsal horn. The first and second sacral segments contained the largest numbers of retrogradely labeled neurons in the spinal cord. The number of spinohypothalamic tract neurons observed in this study in cats was roughly an order of magnitude smaller than that previously reported for rats. This finding suggested either that the spinohypothalamic tract is relatively small in cats or that our tracing techniques did not label many spinohypothalamic tract neurons in cats. To test the sensitivity of one of our tracing techniques, control injections of wheat germ agglutinin conjugated to horseradish peroxidase that filled the ventrobasal thalamus were made in two cats. In both cases, thousands of spinal cord neurons were labeled. In summary, our results indicate that a spinohypothalamic tract exists in cats. However, our findings also suggest that the total number of spinohypothalamic tract neurons in cats may be an order of magnitude smaller than it is in rats.

Evidence that Fluoro-Gold can be transported avidly through fibers of passage.

Small iontophoretic injections of the retrograde tracer Fluoro-Gold were restricted to the dorsal columns in the cervical enlargement of 6 rats. Large numbers of neurons were labeled in the lumbosacral dorsal horn in each rat. In the most effective case, more than 1800 neurons were labeled in alternate sections through nine examined segments. Many neurons were also labeled in lumbosacral dorsal root ganglia of all cases. This study, in contrast to previous reports, indicates that Fluoro-Gold can be transported avidly by axons passing through, but not terminating in, injection sites.

Afferent input to nucleus submedius in rats: retrograde labeling of neurons in the spinal cord and caudal medulla.

In cats, spinal and medullary input to the thalamic nucleus submedius (Sm) arises almost exclusively from neurons in the marginal zone. As a result, it has been proposed that Sm may be specifically involved in nociception. In the present study, we determined the locations of neurons in the spinal cord and caudal medulla that project to Sm in rats. Iontophoretic injections of Fluoro-Gold or pressure injections of Fast blue were made into Sm. In each of the 6 rats that received small injections of Fluoro-Gold into Sm, only a small number (mean = 90) of retrogradely labeled neurons were found throughout the 18 segments of the spinal cord examined. Surprisingly, almost no labeled neurons (less than 1%) were counted in the marginal zone of the spinal cord. The majority were located in the deep dorsal horn and intermediate zone/ventral horn. In contrast, many neurons were labeled in the marginal zone of nucleus caudalis. Injections of Fluoro-Gold into any of a number of nuclei near Sm also labeled only a small number of neurons in the spinal cord and almost no neurons in the marginal zone. Using identical injection parameters, we injected Fluoro-Gold into the ventrobasal complex or posterior thalamic group. Hundreds of neurons in the spinal cord, including many in the marginal zone, were labeled following these injections. These results indicate that the techniques used to inject Fluoro-Gold into Sm were capable of labeling many projection neurons, including those in the marginal zone. Larger pressure injections of Fast blue were also made into Sm of 3 rats. The distribution of labeled neurons in nucleus caudalis and the spinal cord was similar to that following iontophoretic injections of Fluoro-Gold. Again, few marginal zone neurons were labeled in the spinal cord in any of these rats. Therefore, our results indicate that few spinothalamic tract neurons appear to project to Sm or any of several adjacent nuclei, and virtually no marginal zone neurons in the spinal cord project to these areas.