Postsynaptic Dorsal Column Research Articles

Postsynaptic dorsal column pathway activation during spinal cord stimulation in patients with chronic pain.

Spinal cord stimulation (SCS) treatment for chronic pain relies on the activation of primary sensory fibres ascending to the brain in the dorsal columns. While the efficacy of SCS has been demonstrated, the precise mechanism of action and nature of the fibres activated by stimulation remain largely unexplored. Our investigation in humans with chronic neuropathic pain undergoing SCS therapy, found that post-synaptic dorsal column (PSDC) fibres can be activated synaptically by the primary afferents recruited by stimulation, and axonically by the stimulation pulses directly. Synaptic activation occurred in 9 of the 14 patients analysed and depended on the vertebral level of stimulation. A clear difference in conduction velocities between the primary afferents and the PSDC fibres were observed. Identification of PSDC fibre activation in humans emphasises the need for further investigation into the role they play in pain relief and the sensory response sensation (paraesthesia) experienced by patients undergoing SCS.

The encoding of touch by somatotopically aligned dorsal column subdivisions

The somatosensory system decodes a range of tactile stimuli to generate a coherent sense of touch. Discriminative touch of the body depends on signals conveyed from peripheral mechanoreceptors to the brain through the spinal cord dorsal column and its brainstem target, the dorsal column nuclei (DCN)1,2. Models of somatosensation emphasize that fast-conducting low-threshold mechanoreceptors (LTMRs) innervating the skin drive the DCN3,4. However, postsynaptic dorsal column (PSDC) neurons within the spinal cord dorsal horn also collect mechanoreceptor signals and form a second major input to the DCN5–7. The significance of PSDC neurons and their contributions to the coding of touch have remained unclear since their discovery. Here we show that direct LTMR input to the DCN conveys vibrotactile stimuli with high temporal precision. Conversely, PSDC neurons primarily encode touch onset and the intensity of sustained contact into the high-force range. LTMR and PSDC signals topographically realign in the DCN to preserve precise spatial detail. Different DCN neuron subtypes have specialized responses that are generated by distinct combinations of LTMR and PSDC inputs. Thus, LTMR and PSDC subdivisions of the dorsal column encode different tactile features and differentially converge in the DCN to generate specific ascending sensory processing streams.

Mechanoreceptor signal convergence and transformation in the dorsal horn flexibly shape a diversity of outputs to the brain

The encoding of touch in the spinal cord dorsal horn (DH) and its influence on tactile representations in the brain are poorly understood. Using a range of mechanical stimuli applied to the skin, large-scale invivo electrophysiological recordings, and genetic manipulations, here we show that neurons in the mouse spinal cord DH receive convergent inputs from both low- and high-threshold mechanoreceptor subtypes and exhibit one of six functionally distinct mechanical response profiles. Genetic disruption of DH feedforward or feedback inhibitory motifs, comprised of interneurons with distinct mechanical response profiles, revealed an extensively interconnected DH network that enables dynamic, flexible tuning of postsynaptic dorsal column (PSDC) output neurons and dictates how neurons in the primary somatosensory cortex respond to touch. Thus, mechanoreceptor subtype convergence and non-linear transformations at the earliest stage of the somatosensory hierarchy shape how touch of the skin is represented in the brain.

Identification of Spinal Neurons Contributing to the Dorsal Column Projection Mediating Fine Touch and Corrective Motor Movements

Tactile stimuli are integrated and processed by neuronal circuits in the deep dorsal horn of the spinalcord. Several spinal interneuron populations have been implicated in tactile information processing. However, dorsal horn projection neurons that contribute to the postsynaptic dorsal column (PSDC) pathway transmitting tactile information to the brain are poorly characterized. Here, we show that spinal neurons marked by the expression of Zic2creER mediate light touch sensitivity and textural discrimination. A subset of Zic2creER neurons are PSDC neurons that project to brainstem dorsal column nuclei, and chemogenetic activation of Zic2 PSDC neurons increases sensitivity to light touch stimuli. Zic2 neurons receive direct input from the cortex and brainstem motor nuclei and are required for corrective motor movements. These results suggest that Zic2 neurons integrate sensory input from cutaneous afferents with descending signals from the brain to promote corrective movements and transmit processed touch information back to the brain. VIDEO ABSTRACT.

Assessment of axonal recruitment using model-guided preclinical spinal cord stimulation in the ex vivo adult mouse spinal cord

Spinal cord stimulation (SCS) is used clinically to limit chronic pain, but fundamental questions remain on the identity of axonal populations recruited. We developed an ex vivo adult mouse spinal cord preparation to assess recruitment following delivery of clinically analogous stimuli determined by downscaling a finite element model of clinical SCS. Analogous electric field distributions were generated with 300-µm × 300-µm electrodes positioned 200 µm above the dorsal column (DC) with stimulation between 50 and 200 µA. We compared axonal recruitment using electrodes of comparable size and stimulus amplitudes when contacting the caudal thoracic DC and at 200 or 600 μm above. Antidromic responses recorded distally from the DC, the adjacent Lissauer tract (LT), and in dorsal roots (DRs) were found to be amplitude and site dependent. Responses in the DC included a unique component not seen in DRs, having the lowest SCS recruitment amplitude and fastest conduction velocity. At 200 μm above, mean cathodic SCS recruitment threshold for axons in DRs and LT were 2.6 and 4.4 times higher, respectively, than DC threshold. SCS recruited primary afferents in all (up to 8) caudal segments sampled. Whereas A and C fibers could be recruited at nearby segments, only A fiber recruitment and synaptically mediated dorsal root reflexes were observed in more distant (lumbar) segments. In sum, clinically analogous SCS led to multisegmental recruitment of several somatosensory-encoding axonal populations. Most striking is the possibility that the lowest threshold recruitment of a nonprimary afferent population in the DC are postsynaptic dorsal column tract cells (PSDCs) projecting to gracile nuclei.NEW & NOTEWORTHY Spinal cord stimulation (SCS) is used clinically to control pain. To identify axonal populations recruited, finite element modeling identified scaling parameters to deliver clinically analogous SCS in an ex vivo adult mouse spinal cord preparation. Results showed that SCS first recruited an axonal population in the dorsal column at a threshold severalfold lower than primary afferents. These putative postsynaptic dorsal column tract cells may represent a previously unconsidered population responsible for SCS-induced paresthesias necessary for analgesia.

Punctate Midline Myelotomy Reduces Pain Responses in a Rat Model of Lumbar Spine Pain: Evidence that the Postsynaptic Dorsal Column Pathway Conveys Pain from the Axial Spine.

Punctate midline myelotomy (PMM) has been successfully applied clinically in humans for the relief of intractable visceral pain. The operation is thought to work by interrupting the postsynaptic dorsal column pathway (PSDC) of the spinal cord. In fact, PMM was developed specifically for that purpose after it was demonstrated in rats that the PSDC conveyed about 90% of the visceral pain information to the thalamus. The application of PMM also to the problem of severe intractable back or spine pain was never tested, and it has never been established whether the PSDC pathway relates only to visceral pain or whether there may be a broader involvement with pain affecting structures of embryological midline origin, perhaps including the spine. Retrospective analyses of decades of results from various attempted myelotomy procedures in man for the relief of pain are consistent with the notion that the common element crucial to the successful midline or visceral pain relief was the interruption--even incomplete--of the PSDC pathway. Herein, we present evidence from a rat model of lumbar facet pain that interruption of the PSDC significantly reduces pain responses. The implications for the possible treatment of severe intractable spine pain in man are discussed.

Axons of Individual Dorsal Horn Neurons Bifurcated to Project in Both the Anterolateral and the Postsynaptic Dorsal Column Systems

Sensory information stimulates receptors of somatosensory system neurons generating a signal that codifies the characteristics of peripheral stimulation. This information reaches the spinal cord and is relayed to supra-spinal structures through two main systems: the postsynaptic dorsal column-medial lemniscal (DC-ML) and the anterolateral (AL) systems. From the classical point of view, the DC-ML has an ipsilateral ascending pathway to the Gracilis (GRA) or Cuneate (CUN) nuclei and the AL has a contralateral ascending pathway to the ventral posterolateral (VPL) thalamic nucleus. These two systems have been the subject of multiple studies that established their independence and interactions. To analyze the ascending projections of L1–L5 spinal dorsal horn neurons in the rat, two retrograde neuronal tracers were injected into the GRA and the VPL. Additionally, an electrophysiological study was performed by applying electrical stimulation at the GRA or VPL and recording antidromic evoked activity in single unit spinal cord cells. Importantly, a subset of spinal dorsal horn neurons exhibited double staining, indicating that these neurons projected to both the GRA and the VPL. These double-stained neurons were located on both sides of the dorsal horn of the spinal cord. The spinal dorsal horn neurons exhibited antidromic and collision activities in response to both GRA and VPL electrical activation. These results show spinal cord neurons with bifurcated bilateral projections to both the DC-ML and AL systems. Based on these results, we named these neurons bilateral and bifurcated cells.

Single high‐concentration capsaicin application prevents c‐Fos expression in spinothalamic and postsynaptic dorsal column neurons after surgical incision

Allodynia and hyperalgesia present after surgical interventions are often a major complain of surgical patients. It is thought that both peripheral and central mechanisms contribute to these symptoms. In this study, the role of peripheral nerve fibres that express transient receptor potential vanilloid 1 (TRPV1) receptors in the activation of spinothalamic tract (STT) and postsynaptic dorsal column (PSDC) neurons was assessed in a model of surgical pain. Spinothalamic tract and PSDC neurons retrogradely labelled from the thalamus and nucleus gracilis were used. Activation of these projection neurons was evaluated after plantar incision as expression of the early gene product, c-Fos protein, in the nuclei of these neurons. There was a robust increase in c-Fos immunopositivity in the STT and PSDC neurons, in the control animals after a plantar incision. This increase in c-Fos expression was significantly attenuated in animals in which a single high-concentration capsaicin injection was made intradermally at the incision site 24h before the surgery. Our results suggest that activation of both STT and PSDC neurons is involved in development of pain states present after surgical incision and that TRPV1-containing peripheral nerve fibres are needed for c-Fos expression in these dorsal horn neurons after plantar incision.

Spino‐olivary projections in the rat are anatomically separate from postsynaptic dorsal column projections

The gracile nucleus (GN) and lateral part of rostral dorsal accessory olive (rDAO) are important relays for indirect, postsynaptic dorsal column, and direct ascending pathways, respectively, that terminate as climbing fibers in the “hindlimb-receiving” parts of the C1 and C3 zones in the cerebellar cortex. While the spinal cells of origin of that project to GN and rDAO are from largely separate territories in the spinal cord, previous studies have indicated that there could be an area of overlap between these two populations in the medial dorsal horn. Given the access of these two ascending tracts to sensory (thalamic) versus sensorimotor (precerebellar) pathways, the present study therefore addresses the important question of whether or not individual neurons have the potential to contribute axons to both ascending pathways. A double-fluorescent tracer strategy was used in rats (red Retrobeads and Fluoro-Ruby or green Retrobeads and Fluoro-Emerald) to map the spatial distribution of cells of origin of the two projections in the lumbar spinal cord. The two pathways were found to receive input from almost entirely separate territories within the lumbar cord (levels L3–L5). GN predominantly receives input from lamina IV, while rDAO receives its input from three cell populations: medial laminae V–VI, lateral lamina V, and medial laminae VII–VIII. Cells that had axons that branched to supply both GN and rDAO represented only about 1% of either single-labeled cell population. Overall, the findings therefore suggest functional independence of the two ascending pathways. J. Comp. Neurol. 522:2179–2190, 2014. © 2013 Wiley Periodicals, Inc.

Upper thoracic postsynaptic dorsal column neurons conduct cardiac mechanoreceptive information, but not cardiac chemical nociception in rats

Postsynaptic dorsal column (PSDC) neurons transmit noxious visceral information from the lower thoracic and lumbosacral spinal cord. Cuneothalamic neurons in the PSDC pathway and upper thoracic (T 3–T 4) spinal neurons ascending through the ventrolateral funiculus (VLF) have been shown to transmit nociceptive cardiac information. Therefore, we hypothesized that upper thoracic PSDC neurons transmit noxious cardiac information. Neuronal responses to intrapericardially injected mechanical (1.0 ml saline) and noxious chemical (0.2 ml algogenic chemicals) stimuli were recorded from antidromically activated PSDC and VLF neurons in the T 3–T 4 spinal cord of anesthetized Sprague–Dawley rats. Of the PSDC neurons, 43% responded to mechanical stimulation, but only one responded to noxious chemical stimuli. Fifty-eight percent of VLF neurons responded to mechanical stimulation and all responded to noxious chemical stimulation. Fluoro-Ruby (FR)-labeled PSDC neurons in the T 3–T 4 spinal cord of Sprague–Dawley rats were processed for c-fos immunohistochemistry following intrapericardial stimulation with mechanical, chemical, or control stimuli. Sections were viewed under epifluorescence and light microscopy to detect FR-labeled neurons containing a c-fos immunoreactive (IR) nucleus. An average of 6 PSDC neurons per rat was found in the T 3 and T 4 spinal segments. The average number of c-fos-IR neurons per segment varied by type of stimulus: 12 (control), 67 (chemical) and 85 (mechanical) for T 3 and 8 (control), 37 (chemical) and 62 (mechanical) for T 4. None of the 200 PSDC neurons examined expressed c-fos-IR regardless of stimulus. Together, these results suggest that thoracic PSDC neurons transmit mechanical cardiac information, but they play a minimal role in cardiac nociception.

NK-1-receptor-mediated lesion of spinal post-synaptic dorsal column neurons might improve intractable visceral pain of cancer origin

The cancer-related visceral pain has traditionally been frustrating to treat by either medical or surgical means. Recent investigations from bench and bedside have suggested that a critical visceral nociceptive pathway originates from post-synaptic dorsal column (PSDC) neurons located in the central area of the spinal-cord. Interruption of the PSDC pathway using different surgical approaches effectively relieves intractable visceral pain in cancer patients. However, the indications of surgical lesion of DC are very limited in clinical setting because of the surgical risks and complications. Thus, a means of high-specific pharmacological lesion of DC pathway is necessary. Some evidence has shown that spinal PSDC neurons start to express neurokinin-1 (NK-1) receptors after visceral stimulation, suggesting new targets for the development of pharmacological strategies for the control of visceral pain. Here, we present our hypothesis that the targeted cytoxin composed of substance P coupled to the cytotoxic ribosome inactivating protein, saporin, might selectively destroy spinal PSDC neurons expressing NK-1 receptors, which will lead to pharmacological interruption of PSDC pathway and will greatly improve intractable visceral pain of cancer origin. Based on the data from related research, we believe that the current therapy we propose might be one of the optimal pharmacological approaches to replace the neurosurgical interruption of DC pathway and could be used for cancer-related visceral pain in wider clinical indications.

Comparison of activity characteristics of the cuneate nucleus and thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in rats

Previous studies have shown that the gracile nucleus in postsynaptic dorsal column pathway plays an important role in conveying nociceptive information from pelvic visceral organs. The purpose of this study was to compare effects of a noxious cardiac stimulus on neuronal activity in the cuneate nucleus and upper thoracic spinal cord in rats. Extracellular potentials of single neurons in the cuneate nucleus and upper thoracic (T3) spinal cord were recorded in pentobarbital anesthetized, ventilated and paralyzed male rats. To activate cardiac nociceptors, a silicone tube was placed in the pericardial sac over the left ventricle to administer a solution of bradykinin (10 μg/ml, 0.2 ml, 1 min). The number of cuneate neurons responding to intrapericardial bradykinin (IB, 15.6%, 17/109) was significantly less than for T3 neurons (43.2%, 48/111, P < 0.05). IB excited 9/17 (52.9%) cuneate neurons and inhibited eight neurons. In contrast, IB excited a significantly higher percentage of responding spinal neurons than those in cuneate nucleus (43/48, 89.6%, P < 0.01). The ratio of short latency/long-lasting responses of cuneate neurons to IB (14/3) were significant higher than responses of spinal neurons (26/22, P < 0.05). Spontaneous activity (5.5 ± 0.7 imp/s), response amplitudes (6.0 ± 0.6 imp/s) and durations (83.4 ± 10.8 sec) of cuneate neurons excited by IB were significantly less than for spinal neurons (11.5 ± 1.3 imp/s, 20.4 ± 2.0 imp/s and 104.9 ± 7.0 imp/s, P < 0.01, P < 0.01, P < 0.05), respectively. These results indicate that the cuneate nucleus neurons play a relatively minor role in transmission of cardiac nociceptive information in comparison to upper thoracic spinal neurons.

Evidence for the involvement of the spinoparabrachial pathway, but not the spinothalamic tract or post-synaptic dorsal column, in acute bone nociception

We have previously reported that acute noxious mechanical stimulation of bone activates neurons throughout the dorsal horn of the lumbar spinal cord, and argued that the spinal mechanisms that mediate bone nociception are different to those that mediate cutaneous and visceral nociception. In the present study, we provide evidence that the ascending spinal pathways that mediate acute bone nociception also differ to those that mediate acute cutaneous and visceral nociception. Injections of a retrograde tracer (Fluorogold) were made into the thalamus, gracile nucleus or lateral parabrachial nucleus to identify spinothalamic, post-synaptic dorsal column or spinoparabrachial projection neurons respectively (n=4 in each group). Spinal dorsal horn neurons activated by acute noxious mechanical stimulation of bone (bone drilling) were identified in these animals using Fos immunohistochemistry. Fluorogold and Fos-like immunoreactivity was not colocalized in any dorsal horn neurons projecting to the thalamus or gracile nucleus. In contrast, a total of 12.2+/-1.1% (mean+/-S.E.M.) of the spinoparabrachial projection neurons contained Fos-like immunoreactive nuclei following bone drilling and this was significantly greater than the percentage (3.4+/-0.5%) in animals of a sham surgery group (n=4) that were not exposed to bone drilling (Mann-Whitney; p<0.05). These data provide evidence for the involvement of the spinoparabrachial pathway, but not the spinothalamic or post-synaptic dorsal column pathways, in the relay of information regarding acute noxious mechanical stimuli applied to bone, and suggest that spinal pathways that mediate acute bone nociception may be different to those that mediate acute nociception of cutaneous and visceral origin.

Nociceptive spinothalamic tract and postsynaptic dorsal column neurons are modulated by paraventricular hypothalamic activation

Previously, we demonstrated that stimulation of the paraventricular hypothalamic nucleus diminishes the nociceptive dorsal horn neuronal responses, and this decrease was mediated by oxytocin in the rat. In addition, we have proposed that oxytocin indirectly inhibits sensory transmission in dorsal horn neurons by exciting spinal inhibitory GABAergic interneurons. The main purpose of the present study was to identify which of the neurons projecting to supraspinal structures to transmit somatic information are modulated by the hypothalamic-spinal descending activation. In anaesthetized rats, single-unit extracellular and juxtacellular recordings were made from dorsal horn lumbar segments, which receive afferent input from the toe and hind-paw regions. The projecting spinothalamic tract and postsynaptic dorsal column system were identified antidromically. Additionally, in order to label the projecting dorsal horn neurons, we injected fluorescent retrograde neuronal tracers into the ipsilateral gracilis nucleus and contralateral ventroposterolateral thalamic nucleus. Hence, juxtacellular recordings were made to iontophoretically label the recorded neurons with a fluorescent dye and identify the recorded projecting cells. We found that only nociceptive evoked responses in spinothalamic tract and postsynaptic dorsal column neurons were significantly inhibited (48.1 +/- 4.6 and 47.7 +/- 8.2%, respectively) and non-nociceptive responses were not affected by paraventricular hypothalamic nucleus stimulation. We conclude that the hypothalamic-spinal system selectively affects the transmission of nociceptive information of projecting spinal cord cells.

(105) The role of phosphorylation of PKC kinase in signaling nisceral Nociception in spinal PSDC pathway

The aim of this study is to investigate the neuronal phospho-PKC kinase involved in signal transduction of spinal cord and post-synaptic dorsal column (PSDC) pathway in a rat model of visceral pain. Visceral painful stimulation causes spinal neuro-plasticity changes and neuronal calcium-dependent protein kinase (PKC)-mediated neuronal signaling pathway may contribute to the central mechanism of visceral pain. Recent clinical data suggested that neurosurgical interruption of PSDC pathway by performing midline myelotomy in patients with severe cancer pain can greatly alleviate intractable visceral pain.

T1434 Sex Differences in the Characteristics and Role of the Postsynaptic Dorsal Column (PSDC) Pathway in Visceral Pain

T1434 Sex Differences in the Characteristics and Role of the Postsynaptic Dorsal Column (PSDC) Pathway in Visceral Pain

Effects of General Anesthetics on Visceral Pain Transmission in the Spinal Cord

Current evidence suggests an analgesic role for the spinal cord action of general anesthetics; however, the cellular population and intracellular mechanisms underlying anti-visceral pain by general anesthetics still remain unclear. It is known that visceral nociceptive signals are transmited via post-synaptic dorsal column (PSDC) and spinothalamic tract (STT) neuronal pathways and that the PSDC pathway plays a major role in visceral nociception. Animal studies report that persistent changes including nociception-associated molecular expression (e.g. neurokinin-1 (NK-1) receptors) and activation of signal transduction cascades (such as the protein kinase A [PKA]-c-AMP-responsive element binding [CREB] cascade)-in spinal PSDC neurons are observed following visceral pain stimulation. The clinical practice of interruption of the spinal PSDC pathway in patients with cancer pain further supports a role of this group of neurons in the development and maintenance of visceral pain. We propose the hypothesis that general anesthetics might affect critical molecular targets such as NK-1 and glutamate receptors, as well as intracellular signaling by CaM kinase II, protein kinase C (PKC), PKA, and MAP kinase cascades in PSDC neurons, which contribute to the neurotransmission of visceral pain signaling. This would help elucidate the mechanism of antivisceral nociception by general anesthetics at the cellular and molecular levels and aid in development of novel therapeutic strategies to improve clinical management of visceral pain.

A population of large neurons in laminae III and IV of the rat spinal cord that have long dorsal dendrites and lack the neurokinin 1 receptor.

The dorsal horn of the rat spinal cord contains a population of large neurons with cell bodies in laminae III or IV, that express the neurokinin 1 receptor (NK1r) and have long dorsal dendrites that branch extensively within the superficial laminae. In this study, we have identified a separate population of neurons that have similar dendritic morphology, but lack the NK1r. These cells also differ from the NK1r-expressing neurons in that they have significantly fewer contacts from substance P-containing axons and are not retrogradely labelled following injection of tracer into the caudal ventrolateral medulla. We also provide evidence that these cells do not belong to the postsynaptic dorsal column pathway or the spinothalamic tract. It is therefore likely that these cells do not have supraspinal projections. They may provide a route through which information transmitted by C fibres that lack neuropeptides is conveyed to deeper laminae. The present findings demonstrate the need for caution when attempting to classify neurons solely on the basis of somatodendritic morphology.

Spinal Cord Stimulation Modulates Visceral Nociception and Hyperalgesia via the Spinothalamic Tracts and the Postsynaptic Dorsal Column Pathways: A Literature Review and Hypothesis

Introduction. Early animal and human evidence existed for a postsynaptic dorsal column (PSDC) pathway for visceral nociception that, when lesioned, decreased pain of terminal illness. There have been recent anecdotal reports in the literature that spinal cord stimulation (SCS) reduces pain of visceral nociception. We present here a review of the literature supporting a hypothesis that SCS might work by modulating information through the spinothalamic tracts (STT) and PSDC. Methods. A review of the relevant literature regarding nociception, nociceptive transmission, visceral sensitization, and the "brain-gut" axis; and SCS was performed as a foundation for this hypothesis. Key words used for this review of databases and nonindexed relevant journals included visceral pain, visceral nociception, visceral hyperalgesia, visceral neuropathic pain, visceral sensitization, "brain-gut" axis, SCS, PSDC pathway, and STTs. Results. An abundance of both clinical and scientific literature suggests the neuropathic and sensitized nature of chronic visceral nociception. There is also evidence that there may be an interaction between the PSDC pathway and lateral spinothalamic tracts (LSTT) that might be operant in the preclinical and anecdotal clinical evidence that SCS ameliorates the pain of visceral nociception. Conclusions. Chronic visceral nociception may be secondary to visceral sensitization and hyperalgesia and can be affected by the spinal cord and brain, the "brain-gut" axis. There is preclinical evidence and clinical anecdotes that this nociceptive information is transmitted in the central nervous system through the PSDC pathway and LSTT and that SCS decreases pain of visceral nociception. It may be that SCS works by modulation of the above pathways.

Coeruleospinal inhibition of visceral nociceptive processing in the rat spinal cord

Visceral nociceptive information is transmitted in two different areas of the spinal cord gray matter, the dorsal horn and the area near the central canal. The present study was designed to examine whether visceral nociceptive transmission in the two different areas is under the control of the centrifugal pathways from the locus coeruleus/subcoeruleus (LC/SC). Extracellular recordings were made from the L(6)-S(2) segmental level using a carbon filament glass microelectrode (4-6 MOmega). Colorectal distentions (80 mmHg) were produced by inflating a balloon inside the descending colon and rectum. In both dorsal horn and deep area neurons, responses to colorectal distention were inhibited during electrical stimulation (30, 50 and 70 microA, 100 Hz, 0.1 ms pulses) of the LC/SC. It is well known that spinothalamic tract (STT) neurons excited by visceral nociceptive stimuli are located in the dorsal horn and that postsynaptic dorsal column (PSDC) neurons which conduct visceral nociceptive signals in the dorsal column (DC) are located near the central canal of the spinal cord. The present study, therefore, suggests that the descending LC/SC system can inhibit visceral nociceptive signals ascending through the STT and the DC pathways.