The effect of morphine on responses of ventrolateral orbital cortex (VLO) neurons to colorectal distension in the rat

In 49 halothane-anesthetized rats, we characterized the responses of single neurons in the ventrolateral orbital cortex (VLO) to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of intravenous morphine on these responses using standard extracellular microelectrode recording techniques. One hundred and four neurons were isolated on the basis of spontaneous activity. Fifty-seven (55%) responded to CRD, of which 32% had excitatory and 68% had inhibitory responses. Neurons showed tendencies toward graded responses to graded CRD pressures (20–100 mmHg), with maximum excitation or inhibition occurring at 80 or 100 mmHg, respectively. Responses to noxious (pinch, heat) and innocuous (brush, tap) cutaneous stimuli were studied in 80 of the VLO neurons isolated. Thirty-three (41%) of these neurons (21 CRD-responsive and 12 CRD-nonresponsive) had cutaneous receptive fields, of which 79% were large and bilateral, 18% were small and bilateral, 3% were small and ipsilateral. Ninety-four percent of these neurons responded only to noxious cutaneous stimulation, 6% responded to both noxious and innocuous stimulation. No neurons responded solely to innocuous stimulation. Cumulative doses of morphine (0.0625, 0.125 and 0.25 mg/kg i.v.) produced statistically significant dose-dependent attenuation of neuronal responses to CRD. Naloxone (0.4 mg/kg i.v.) reversed the effects of morphine. Morphine and naloxone had no significant effects on spontaneous activity. These data support the involvement of VLO neurons in visceral nociception.     

Electrical stimulation of thalamic Nucleus Submedius inhibits responses of spinal dorsal horn neurons to colorectal distension in the rat

In 78 halothane-anesthetized rats, we characterized the responses of single neurons in the dorsal horn of L(6)-S(1) spinal segments to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of focal electrical stimulation of Nucleus Submedius (Sm) on these responses using standard extracellular microelectrode recording techniques. A total of 102 neurons were isolated on the basis of spontaneous activity. Eighty (78%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. Neurons showed graded responses to graded CRD pressures (20-100 mmHg), with maximum excitation or inhibition occurring at 100 mmHg. Responses to noxious (pinch, heat) and innocuous (brush, tap) cutaneous stimuli were studied in 73 of the spinal dorsal horn neurons isolated. Fifty-seven (78%) of these neurons (46 CRD-responsive and 11 CRD-nonresponsive) had cutaneous receptive fields, of which 35 (61%) were small and ipsilateral, 14 (25%) were large and ipsilateral, 7 (12%) were large or small and bilateral, and 1 (2%) was small and contralateral. Sixty-one percent of these neurons responded to both noxious and innocuous cutaneous stimulation, 35% responded only to noxious stimulation, and 4% responded only to innocuous stimulation. Electrical stimulation (50-300 microA) of the contralateral Sm produced intensity-dependent attenuation of the CRD-evoked activities of most neurons (18/28 of CRD-excited and 7/12 of CRD-inhibited) tested. Sm stimulation produced facilitation of CRD responses of only one neuron (CRD-inhibited). Sm stimulation had no effects on spontaneous activity. These data indicate that Sm may be involved in the descending inhibitory modulation of visceral nociception at the spinal level.     

The effect of morphine on responses of mediodorsal thalamic nuclei and nucleus submedius neurons to colorectal distension in the rat

In halothane-anesthetized rats, we characterized the responses of single neurons in the nuclei of medial thalamus (MT), specifically the mediodorsal thalamic nucleus (MD) and the nucleus submedius (Sm), to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of intravenous morphine (Mor) on these responses using standard extracellular microelectrode recording techniques. 62 MD and 46 Sm neurons were isolated on the basis of spontaneous activity. 47 of the MD neurons (76%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. 38 of the Sm neurons (83%) responded to CRD, of which 89% had excitatory and 11% had inhibitory responses. Responses of MD and Sm neurons excited by CRD were related significantly to distension pressure (20–100 mmHg), with maximum excitation occurring at 60 and 100 mmHg, respectively. MD neurons inhibited by CRD also had graded responses to graded CRD, with maximum inhibition occurring at 80 mmHg. The responses to noxious (pinch, heat) and nonnoxious (tap, brush) cutaneous stimuli were studied in 59 of the MD and 44 of the Sm neurons isolated. 22 of the MD neurons (37%) studied had cutaneous receptive fields, of which 59% were large and bilateral, 41% were small and usually contralateral receptive fields. 55% of these neurons were nociceptive-specific, 45% responded to both noxious and nonnoxious cutaneous stimulation. 29 of the Sm neurons (66%) studied had cutaneous receptive fields, of which 72% were large and usually bilateral, 14% were small and bilateral, 14% were small and contralateral receptive fields. 90% of these neurons were nociceptive-specific, 10% responded to both noxious and nonnoxious stimulation. No MD or Sm neurons responded exclusively to nonnoxious cutaneous stimulation. Mor (0.125, 0.25, 0.5 and 1 mg/kg IV) attenuated MD and Sm neuronal excitatory responses to CRD in a dose-dependent fashion, abolishing evoked activity with a dose of 0.5 mg/kg (p<0.05) and 1 mg/kg (p<0.05), respectively. Naloxone (0.4 mg/kg IV) reversed the effects of Mor. Mor and naloxone had no effects on spontaneous activity. These data support the involvement of MD and Sm neurons in visceral nociception, and are consistent with a role of Sm in affective-motivational, and MD in both sensory-discriminative and affective-motivational aspects of nociception.     

Characterization of responses of primary somatosensory cerebral cortex neurons to noxious visceral stimulation in the rat

In pentobarbital-anesthetized rats, responses of single neurons in primary somatosensory cortex (SI) to graded noxious visceral (colorectal distention, CRD) and cutaneous stimulation were recorded. One-hundred fifteen SI neurons were identified on the basis of spontaneous activity, 66 of which responded to CRD. CRD resulted in facilitation of neuronal activity in 33% and inhibition of activity in 52% of these cells. Fifteen percent had mixed facilitated/inhibited responses to varying CRD pressures. Cutaneous receptive fields were identified in 71% of CRD-responsive neurons, with low-threshold or wide dynamic range responses in most cases. Nearly all cutaneous receptive fields were small contralateral sites. Responses to CRD were independent of neuronal depth within the cortex. These data support a role of primary somatosensory cerebral cortical neurons in visceral nociception.     

大鼠丘脑中央下核及其邻近结构神经元对皮肤伤害性刺激的反应

利用细胞个记录技术，在麻醉大鼠丘脑中央下核（Ｓｍ）及其邻近结构内，共记录到１９２个神经元７８％的神经元对皮肤伤害性刺激反应，其中，大多数（１１８）被兴奋，２８个被抑制，４个对某些部位的刺激兴奋，而对另一些部位的刺激抑制，发现某些神经元有很长的后发放效应，另一些则在兴奋之后跟随着较长的抑制期，少数的反应仅在刺激给与和撤除的瞬间发生，感受野大且呈双侧分部，８０％对机械刺激反应的神经元也对伤害性热刺激发     

Viscerosomatic interactions in the thalamic ventral posterolateral nucleus (VPL) of the squirrel monkey

In anesthetized squirrel monkeys single cell recordings were performed using tungsten microelectrodes. The responses of 29 viscerosomatoceptive and somatoceptive VPL neurons to noxious distension of the urinary bladder, the lower esophagus and the distal colon and to innocuous and noxious somatic stimuli were assessed when these stimuli were presented separately or together. Neuronal responses were defined as additive or interactive depending on the relative changes in responses to individual somatic or visceral stimuli, and on their responses during conditioning (somatic and visceral stimuli applied concurrently). In 13 neurons interactions between the somatosensory and visceral inputs could be demonstrated. The dominant interactive effect was inhibition, although facilitatory effects were seen as well (2 of 13). The magnitude or direction of the interactions seemed independent of the location of the somatic and visceral receptive fields. The mean population response of the neurons showing interactions was 4.66 spikes/s to somatic stimulation, and 0.07 spikes/s to visceral stimulation. During conditioning the mean interactive effect was −62% of the calculated additive effect. This implies that overall the somatic responses are halved during a coincident visceral stimulus. In a subgroup of the VPL neurons, which were classified as pure somatic responsive (n=14) due to their unresponsiveness during visceral stimulation alone, a third (n=5) still exhibited visceral convergence during conditioning. The latter neurons, therefore, receive visceral inputs, which function in a purely interactive (modulatory) manner. It is concluded that part of the described effects is due to competition (cross modality suppression) between the visceral and somatic inputs. We further conclude that the suppression of somatic information by noxious visceral stimuli may contribute to a more effective processing of the discriminatory aspects of nociceptive visceral information previously demonstrated in VPL.     

Modulation of visceral nociceptive responses of rat spinal dorsal horn neurons by sympathectomy

We determined whether sympathectomy modulates visceral nociception under physiological or inflammatory conditions. Recordings of sacral spinal dorsal horn neurons with sustained responses were performed in pentobarbitone-anesthetized rats. Graded colorectal distension (CRD, 20-100 mmHg) was used as a visceral nociceptive stimulus. Inflammation was induced by intracolonic instillation of turpentine (25%). Sympathectomy was produced by administering 6-hydroxydopamine. Inflammation produced an increase in the CRD-evoked responses. The CRD-evoked responses were attenuated following sympathectomy both under control and inflammatory conditions. These changes in the CRD-evoked responses were associated with corresponding changes in spontaneous discharge rate. The convergent input evoked by noxious pinch of the skin was not changed by any of the experimental conditions. The results indicate that sympathectomy attenuates visceral nociceptive responses and spontaneous activity of sacral spinal cord neurons, without effect on convergent cutaneous inputs, both under physiological and inflammatory conditions.     

Evidence for two populations of rat spinal dorsal horn neurons excited by urinary bladder distension

Spinal L6-S2 dorsal horn neurons of cervical spinal cord-transected, decerebrate female rats were characterized using urinary bladder distension (UBD) as a visceral stimulus. Constant pressure, phasic, graded (20-80 mm Hg, 20 s) air UBD was delivered via a transurethral catether and extracellular single-unit recordings obtained from all neurons excited by UBD. Responses to graded UBD and noxious/non-noxious cutaneous stimuli were determined in 258 neurons which could be stratified into two groups based on their effect of a counterirritation stimulus: Type I neurons (n=112) were inhibited by noxious pinch presented in a non-segmental field; Type II neurons (n=146) were not similarly inhibited. Both Types of neurons were identified in both superficial and deep recording sites and demonstrated graded responses to graded UBD. All UBD-excited neurons had convergent cutaneous receptive fields (RFs) excited by non-noxious and/or noxious stimuli. As a group, Type I neurons had a period of decreased activity following termination of the distending stimulus whereas Type II neurons typically had a sustained afterdischarge. UBD-evoked activity in Type II neurons was inhibited more than similar activity in Type I neurons by both intravenous morphine and lidocaine. These results support the assertion that at least two different populations of spinal dorsal horn neurons exist which encode for a stimulus of urinary bladder distension. These populations are an analogue to previously characterized, similar neuronal populations excited by colorectal distension and suggest that they are representative of the overall phenomenon of visceral sensory processing, a component of which is nociception.     

Responses of neurons in ventroposterolateral nucleus of primate thalamus to urinary bladder distension.

The purpose of this study was to examine effects of a noxious visceral stimulus, urinary bladder distension (UBD), on cells in the ventroposterolateral (VPL) nucleus of anesthetized monkeys. We hypothesized that processing of visceral information in the VPL nucleus of the thalamus is similar to spinothalamic tract (STT) organization of visceral afferent input. Urinary bladder distension excites sacral and upper-lumbar STT cells that have somatic input from proximal somatic fields; whereas, thoracic STT cells are inhibited by UBD. Extracellular action potentials of 67 neurons were recorded in VPL nucleus. Urinary bladder distension excited 22 cells, inhibited 9 cells, and did not affect activity of 36 cells. Seventeen of 22 cells excited by UBD also received convergent somatic input from noxious squeeze of the hip, groin, or perineal regions. No cells activated only by innocuous somatic stimuli were excited by UBD. Five of 9 cells inhibited by UBD had upper-body somatic fields. There was a significant tendency for VPL neurons excited by UBD to have proximal lower-body somatic fields that were excited by noxious stimulation of skin and underlying muscle (P less than 0.001). Antidromic activation of 4 thalamic neurons affected by UBD showed that visceral input stimulated by UBD reached the primary somatosensory (SI) cortex.     

Noxious intensities of visceral stimulation are required to activate viscerosomatic multireceptive neurons in the thoracic spinal cord of the cat

Single unit electrical activity has been recorded from neurons in the Th8 and Th9 segments of the spinal cord in chloralose-anesthetized cats. These neurons had cutaneous receptive fields in the right costal region from which they could be driven by noxious and/or innocuous stimulation of the skin. They could also be activated by distensions of the biliary system but only at noxious intensities of visceral stimulation. No viscero-somatic convergent neurons have been found responding to innocuous visceral stimulation.     

A possible synaptic configuration underlying coeruleospinal inhibition of visceral nociceptive transmission in the rat

A synaptic arrangement underlying descending inhibition from the locus coeruleus/subcoeruleus (LC/SC) on visceral nociceptive transmission in the spinal cord was investigated in the anesthetized rat. Extracellular recordings were made from the L₆-S₂ segmental level using a carbon filament glass microelectrode (4–6 MΩ). Colorectal distention (CRD) was produced by inflating a balloon inside the descending colon and rectum. All neurons tested responded to both CRD and to cutaneous pinch (a force of 613 g/mm²), indicating that nociceptive signals from visceral organs and nociceptive signals from the cutaneous receptive field converge on a single neuron. These neurons were divided into two groups based on their response to CRD: short latency-abrupt and short latency-sustained neurons. Electrical stimulation of the LC/SC (30 or 50 μA, 100 Hz, 0.1 ms pulses) inhibited both CRD-evoked and cutaneous pinch-evoked responses in short latency-abrupt and short latency-sustained neurons. When graded CRD (20, 40, 60, and 80 mmHg) was delivered, LC/SC stimulation produced a reduction in slope of the linear CRD intensity-response magnitude curve without a change in the response threshold in both short latency-abrupt (n = 42) and short latency-sustained neurons (n = 11). This result suggests that coeruleospinal inhibition of visceral nociceptive transmission is due to a synaptic configuration in which inhibitory and excitatory terminals are in close spatial proximity, including presynaptic inhibition.     

Intradermal capsaicin inhibits lumbar dorsal horn neuronal responses to colorectal distention

The purpose of this study was to examine the effect of cutaneous inflammation on the responses of viscerosomatic convergent dorsal horn neurons to graded colorectal distension (CRD) and cutaneous mechanical stimulation. Responses of single viscerosomatic neurons in the lumbar dorsal horn of the rat spinal cord to CRD and to cutaneous stimuli were recorded before and 50 min after cutaneous inflammation induced by intradermal injection of capsaicin in the receptive field (RF) or in the ipsilateral and contralateral forepaw. Capsaicin injection in the RF induced an increase in the spontaneous activity of dorsal horn neurons, an expansion in the size of their RF and facilitated their responses to cutaneous stimuli. An injection placed in the center of the RF attenuated the responses to noxious CRD. Capsaicin injection in the forepaw caused a significant decrease in the responses to CRD but not to cutaneous stimuli. These results indicate that the inhibitory effects, evoked by cutaneous inflammation, can modulate the responses of dorsal horn neurons to CRD, independent of its effect on the responses to cutaneous mechanical stimuli.     

Thalamic modulation of visceral nociceptive processing in adult rats with neonatal colon irritation

Visceral pain originates from visceral organs in response to a noxious stimulus which, if prolonged, may lead to chronic changes in the neural network mediating visceral nociception. For instance, colon inflammation enhances the responses of neurons in the thalamus to colorectal distension (CRD), whereas lesion in the dorsal column (DC) reverses this neuronal sensitization, suggesting that the thalamus and the DC play major roles in chronic visceral pain. In this study, we used adult rats sensitized with neonatal painful colon irritation to reveal the contribution of the thalamus and the DC to neuronal hyperexcitability in a model of chronic visceral pain. We recorded the responses of lumbosacral neurons to CRD in control rats and in rats with colon irritation following stimulation or inactivation of the thalamus, and after DC lesion. Our results show that, first, neuronal responses to CRD decreased following thalamic stimulation in control rats, whereas, in rats with colon irritation, responses either decreased or increased; second, DC lesion attenuated or enhanced these effects in the positively or in the negatively modulated group of neurons, respectively; third, lidocaine injection in the thalamus reduced the responses to CRD in some of the neurons recorded in rats with colon irritation, but had no effect on those in control rats. Therefore, it is reasonable to speculate that plasticity in rats with colon irritation that may underlie chronic pain is sustained by feedback loops ascending in the DC and engaging the thalamus.     

Responses of neurons in nucleus ventralis posterolateralis of the cat thalamus' to hypogastric inputs

Recordings were made from 68 units in the nucleus ventralis posterolateralis (VPL) of the cat thalamus, which responded to stimulation of hypogastric afferents. These units also received nociceptive inputs from the contralateral integument. Units which responded exclusively to hypogastric afferent inputs were not found. Thirty seven of the units were nociceptive specific (NS), and the remaining 31 were wide dynamic range (WDR) units. All of these units were located in the shell region of the lateral subdivision of the caudal VPL. NS units responding to hypogastric afferent inputs had a circumscribed cutaneous receptive field on the contralateral abdomen, gluteal region, tail or hind limb. These areas corresponded to tactile dermatomes T13-S2. Similarly, the cutaneous receptive fields of WDR units receiving hypogastric afferent inputs were distributed in the contralateral abdomen, gluteal region, tail and hind limb, with the sole exception of one unit, whose receptive field also included a part of the lower thorax. These findings extend the previous findings that the shell region of the caudal VPL of the cat thalamus constitutes a thalamic link in a visceral pain pathway, and that the visceral and cutaneous pathways share a common projection locus in the VPL.     

Effects of electrical stimulation of thalamic nucleus submedius and periaqueductal gray on the visceral nociceptive responses of spinal dorsal horn neurons in the rat

Electrical stimulation of the nucleus submedius (Sm) has been shown to suppress the viscerosomatic reflex (VSR), which is evoked by colorectal distension (CRD). We have examined the effects of focal electrical stimulation (0.3 ms, 50 Hz, 100 microA, 10 s) of the Sm and the periaqueductal gray (PAG) on the excitatory responses evoked by CRD in spinal dorsal horn neurons within the L6-S1 region in the urethane-anesthetized Wistar rats. Extracellular recordings were made from 32 spinal excitatory CRD responses. All of these neurons were convergent neurons with cutaneous receptive fields. The majority of the neurons (27/32) were wide dynamic range (WDR) neurons (responding to noxious and non-noxious cutaneous stimuli) while the remaining five neurons were nociceptive specific (NS) neurons (responding only to noxious cutaneous stimuli). The effects of electrical stimulation applied to 28 sites within the Sm were assessed for spinal neurons. Electrical stimulation in seven sites within the Sm (25%) inhibited the CRD excitatory response of dorsal horn neurons, while in two sites (7%) the same stimulation yielded facilitation. Electrical stimulation in the majority of the sites in the Sm (19/28, 68%) did not affect spinal excitatory CRD responses. On the other hand, electrical stimulation of the PAG clearly inhibited 20 of 22 (90%) CRD excitatory responses. These results suggest that the majority of Sm neurons may suppress VSR activity at a supraspinal reflex center rather than via a descending inhibition of spinal visceral nociceptive transmission, as is the case for the PAG.     

Electrophysiological properties of ventromedial medulla neurons in response to noxious and non-noxious stimuli in the awake, freely moving rat: a single-unit study

The spontaneous and evoked activities of ventromedial medulla (VMM) neurons have been recorded in the chronic, awake, freely moving rat. The vast majority of neurons located at the level of the nucleus raphé magnus exhibited an irregular and variable (2-16 Hz) spontaneous activity and were activated by either cutaneous or auditory stimuli. Within this convergent neuronal class the neurons were activated by either cutaneous noxious and non-noxious inputs. The threshold for cutaneous activation was likely very low since a majority of units responded to air puffs, but the application of controlled brushing and pin-prick revealed that the VMM convergent neurons responded more for the noxious mechanical stimulation. Similar findings were found with pinch application. For both innocuous and noxious stimuli, the cutaneous receptive field was extremely extensive (almost all of the body); however, the application of the controlled brushing showed that for this innocuous stimulation, the most sensitive regions were the tail, back, snout and vibrissae and, to a lesser extent, the flank and paws. Preliminary experiments indicated that both the spontaneous and evoked activities of VMM convergent neurons were inhibited during stressful manipulations such as scruff lifting or defense reactions. These data contrast with other studies on VMM single unit recordings in anesthetized rats since the majority of these studies did not emphasize the VMM convergent group; in addition, with one exception, we did not find neurons exclusively driven by noxious inputs. Without excluding a role of the VMM convergent group in pain descending control systems, we proposed that this neuronal class is perhaps also involved in pain transmission or in general processess such as alertness and stress. Experiments are proposed in order to precisely determine the involvement of the VMM convergent neurons in alertness versus sensory discriminative aspects of nociception in the awake, freely moving rat.     

Neuronal receptive field properties in feline nucleus reticularis gigantocellularis

Nucleus reticularis gigantocellularis (NGC) has been shown, using both behavioral and physiological techniques, to be involved in the processing of nociceptive information. However, previous studies of the receptive fields of NGC neurons have utilized only innocuous stimuli. Thus, while neurons in NGC may play an important role in nociception, the receptive field properties of these cells remain to be defined. This investigation was designed to determine the receptive field properties of neurons in NGC using nociceptive and innocuous stimuli. Receptive fields were determined for 127 neurons in NGC. Eighty-seven percent of the NGC neurons studied responded exclusively to noxious stimuli, while 13% also responded to innocuous stimuli. None of the neurons studied responded exclusively to innocuous stimuli. The receptive fields of most NGC neurons (63%) were large, discontinuous, and bilaterally symmetrical. Eighty-one percent of NGC neurons received convergent inputs from both spinal and trigeminal systems. These receptive field properties differ from those previously reported using only innocuous stimulation     

Inhibition of rubral neurons by noxious and non-noxious pressure

The role of the red nucleus (RN) in nociception was investigated in this study. Extracellular recordings from spontaneously active RN neurons were conducted in the rat while noxious pressure was delivered to the hindpaws or tail. Cells in the RN were predominantly inhibited by the stimuli. The units were most responsive when noxious pressure was applied to the contralateral hindpaw. Furthermore, more cells in the magnocellular division of the RN responded to the stimuli than cells in the parvocellular division. Delivery of a graded pressure stimulus to the contralateral hindpaw revealed 4 cell types in the RN: non-responsive cells; cells only responsive during the early, non-noxious portion of the stimulus; cells only responsive during the later, noxious portion of the stimulus; and cells that showed an initial response during the non-noxious part of the stimulus and a second, later response during the noxious portion of the stimulus. To further examine the putative role of the RN in nociception, oxotremorine, gamma-aminobutyric acid (GABA), serotonin, glutamate, and morphine were unilaterally microinjected into the RN and the responses of the animals in the tail flick test were assessed. Only morphine produced a significant antinociception in the animals following intrarubral microinjection. However, it is unclear whether this alteration was mediated through the RN because an antinociception of equal magnitude could be elicited from the reticular formation surrounding the RN and lesions of the RN did not alter the antinociception produced by systemic administration of morphine. Although other explanations cannot be ruled out, it appears that the RN may be involved in coordinating the motor response to pain rather than modulating sensory transmission.     

Thalamic nucleus ventro-postero-lateralis inhibits nucleus Parafascicularis response to noxious stimuli through a non-opioid pathway

These experiments investigated the role of a specific thalamic nucleus in the cellular response to noxious and non-noxious inputs. Single-unit extracellular responses to peripheral noxious stimuli were recorded with glass micropipettes in the nucleus parafascicularis (Pf) of the rat under chloral hydrate anesthesia. Bipolar stimmulating/recording electrodes were inserted in the nucleus ventro-posterolateralis (VPL) of the thalamus, in areas responsive to the peripheral noxious stimulation. Single-unit records in Pf and multi-unit records in VPL demonstrated that both these nuclei are differentially sensitive to noxious and non-noxious inputs: Pf was more sensitive to late (200–600 ms latency) high threshold noxious inputs, while VPL was more responsive to early (10–40 ms) low threshold non-noxious inputs. Late, high threshold inputs to VPL were selectively suppressed by systemic morphine and restored by naloxone. Trains of stimuli applied to VPL suppressed the response of 76% of Pf units, to peripheral noxious stimuli but did not inhibit the response of spinal cord dorsal horn units to the same stimuli. This inhibitory effect of VPL on Pf cells was not reversed by systemically administered naloxone. The neural pathways responsible for the VPL suppression of Pf nociception appear to be neither monosynaptic nor mediated through the spinal cord dorsal horn, nor through any single, naloxone-reversible, central opioid process. Nevertheless, this inhibitory effect of VPL stimulation on Pf nociception provides a physiological basis for the analgesic effects of thalamic stimulation on clinically observed deafferentation pain. It also supports the existence of a pain modulating system at the thalamic level comparable, at least in part, with the spinal Gate Control concept.     

Response properties of nociceptive and low-threshold mechanoreceptive neurons in the hamster superior colliculus

There are many somatosensory neurons in the hamster superior colliculus (SC); some respond to innocuous tactile stimuli, while others respond either preferentially, or solely, to noxious stimuli. Yet, there are little quantitative data describing the responses of these neurons. We sought to provide such information by relating stimulus intensity to the magnitude of the neural response using controlled innocuous and noxious mechanical and thermal stimuli. Of 122 somatosensory SC neurons studied in urethane-anesthetized hamsters, the majority (52%) had low-threshold mechanoreceptive properties (LT). LT neurons had force thresholds less than 1 gm, adapted rapidly to maintained stimuli, and did not respond with higher numbers of impulses to noxious mechanical or thermal stimuli. A smaller, though substantial, proportion of neurons (45%) responded either preferentially, or solely, to noxious stimuli. A few neurons (3%) were inhibited by either light tactile or noxious mechanical stimuli. Two populations of nociceptive neurons were found and classified either as wide dynamic range (WDR) neurons (n = 25), those that responded to gentle mechanical, noxious mechanical, and/or thermal stimuli; or nociceptive-specific (NS) neurons (n = 30), those that responded solely to high-intensity mechanical or noxious thermal stimuli. WDR neurons responded monotonically to increases in the intensity of innocuous mechanical stimuli, and displacement-response relationship for this population was a slightly negatively accelerating power function with an exponent of 0.785. However, the thermal stimulus-response relationships (to graded skin temperatures) of both WDR and NS neurons were positively accelerating power functions with exponents of 2.3 and 2.5 (r2 = 0.988), respectively. These values are consistent with both electrophysiological data from dorsal horn nociceptive neurons and from human psychophysical results using the same range of thermal stimuli. These experiments demonstrate that SC neurons are capable of signaling not only the presence and location of a noxious stimulus but its intensity as well. Presumably, these neurons play a significant role in the animal's reactions to potentially harmful stimuli. The partial laminar segregation of WDR and NS neurons may reflect different involvements of particular nociceptive subtypes in the various overt responses mediated by the SC.