Low-threshold Neurons Research Articles

The synapse between LE sensory neurons and gill motoneurons makes only a small contribution to the Aplysia gill-withdrawal reflex.

The monosynaptic connection between the mechano-sensory neurons in the LE cluster and gill motoneurons has been extensively studied and used as a model for the gill-withdrawal reflex and its behavioural plasticity. In an attempt to evaluate the contribution of this synapse to the behaviour, we used voltage-sensitive dye recording to determine the number of activated LE neurons and the number of spikes made by each neuron in response to a light touch. In five preparations, light touch activated a median of five sensory cells with a median of 1.6 spikes per cell. From a comparison of the sizes of the motoneuron synaptic potentials elicited by LE spikes and elicited by a light siphon touch, we estimate that the LE sensory neurons contribute approximately 5% of the motoneuron synaptic potential in response to this touch. This result casts doubt on the validity of using this synaptic connection as a model for gill-withdrawal behaviour. Siphon nerve recordings reveal the existence of short-latency, low-threshold neurons that may provide much of the sensory input in response to a light touch.

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)

Opioids modulate N-methyl- d-aspartic acid (NMDA)-evoked responses of neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis)

Extracellular single unit recordings were made from 74 neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis). N-methyl- d-aspartic acid (NMDA) excited nociceptive as well as non-nociceptive neurons. NMDA receptor antagonist, dl-2-Amino-5-Phosphonovaleric acid (AP-5), blocked the NMDA-evoked excitation. Microiontophoretic application of a selective μ-opioid receptor agonist, [ d-Ala 2,N-Me-Phe 4,Gly 5-ol]lenkephalin (DAMGO), reduced the NMDA-evoked responses of 100% of nociceptive specific (NS), 93% of wide dynamic range (WDR) and 86% of low threshold (LT) neurons in the superficial and deeper dorsal horn of the medulla. In contrast, application of a selective δ 1-opioid receptor agonist, [ d-Pen 2,5]enkephalin (DPDPE), reduced the NMDA-evoked responses of 90% of NS neurons, 72% of WDR neurons and 67% of LT neurons in the superficial and deeper dorsal horn of the medulla. DPDPE also produced excitatory or biphasic effects. The inhibitory actions of DAMGO and DPDPE were reversed by naloxone and/or 7-benzylidenenaltrexone (BNTX), μ- and δ 1-receptor antagonists. It is concluded that μ- and σ-opioid receptor agonists produce a predominantly inhibitory modulation of the NMDA-evoked responses of nociceptive and non-nociceptive neurons in the medullary dorsal horn.

Differential effects of spinalization on discharge patterns and discharge rates of simultaneously recorded nociceptive and non-nociceptive spinal dorsal horn neurons

Recordings were made simultaneously from 2–5 neurons at the same site in the lumbar spinal dorsal horn of pentobarbital-anesthetized rats. Neurons were classified as low-threshold (LT) or multireceptive (MR) according to their responses to non-noxious mechanical or noxious radiant heat stimuli of the skin. At the same recording sites neurons could be encountered which belong to different classes and/or which had mechanoreceptive fields which did not overlap. Cold blocks of the upper or lower thoracic cord or transsections of the upper cervical cord were made to evaluate the effects of spinalization on both the rate and pattern of background activity and/or noxious heat-evoked responses of different dorsal horn neurons under identical experimental conditions. At 24 of 27 recording sites, spinalization had qualitatively or quantitatively different effects on the rate of background activity of simultaneously recorded neurons. Interspike interval (ISI) means of background activity were significantly reduced in 29 of 65 (44.6%) neurons, prolonged in 23 of 65 (35.4%) neurons, or unchanged in 13 of 65 (20%) neurons. MR neurons displayed a significantly higher incidence of decreased background activity 17 of 45 (37.8%) and a lower incidence of increased background activity (18 of 45, 40%) during spinalization that the LT neurons from which 1 of 12 (8.3%) decreased and 8 of 12 (66.6%) increased background activity. Almost all (95.4%) neurons changed their discharge patterns after spinalization. At 9 of 27 recording sites, the discharge patterns of simultaneously recorded neurons were affected differently by spinalization as revealed by the coefficient of dispersion of the interspike intervals (ISI), indicating changes in the tendency to discharge action potential in clusters (bursts). At the same recording sites the level of noxious heat-evoked responses of simultaneously recorded MR neurons was also differentially affected by spinalization. Nociceptive responses were significantly enhanced in 19 of 37 (51.4%) neurons (137.8 ± 142.6%) of control, mean ± SD), reduced in 13 of 37 neurons (35.1%) (by 58.9 ± 20.9%) and/or unchanged in 5 of 37 (13.5%) neurons. It is concluded that no general ‘tone’ of descending antinociception exists and that tonic descending excitatory and inhibitory systems may be active simultaneously modulating both the level and pattern of neuronal discharges.

Grouping of somatosensory neurons in the spinal cord and the gracile nucleus of the rat by cluster analysis

1. A set of 11 cutaneous stimuli defined previously to differentiate among different types of cutaneous sensory receptors in the rat hindpaw was also effective in differentially activating second-order sensory neurons in the dorsal horn and the gracile nucleus of rats. 2. All sampled units were responsive to more than 1 of the 11 stimuli. However, none responded to innocuous warming or cooling stimuli. Therefore further analysis was restricted to responses to nine of the selected stimuli. 3. Cluster analysis of the responses to nine selected innocuous and noxious mechanical stimuli and noxious thermal stimuli yielded seven classes that seemed functionally distinct from each other: a class of high-threshold neurons, three classes of convergent (wide dynamic range) neurons, a class of a mixture of poorly responsive neurons and neurons receiving Pacinian inputs, and two classes of low-threshold neurons. 4. High-threshold neurons responded predominantly to noxious mechanical and thermal stimuli and presumably received an input from both mechanically and thermally sensitive nociceptors. These cells were located in the dorsal horn, and some were spinothalamic tract cells. Wide dynamic range neurons were excited by innocuous and noxious stimuli, but better by noxious stimuli. These classes of cells were either in the dorsal horn (some were spinothalamic tract cells) or in the nucleus gracilis.(ABSTRACT TRUNCATED AT 250 WORDS)

Two major types of premotoneurons in the feline trigeminal nucleus oralis as demonstrated by intracellular staining with horseradish peroxidase.

Previous studies suggest that neurons in the dorsomedial subdivisions of trigeminal nucleus oralis (Vo) may contribute to reflex control of jaw movements and to modulation of sensory information. The present study has addressed this possibility by the use of intracellular staining with horseradish peroxidase of physiologically identified neurons in Vo to examine functional and morphological properties of these neurons. Of 14 labeled neurons, eight had axon collaterals terminating exclusively in the dorsolateral subdivision of the trigeminal motor nucleus (DL neurons) and four in its ventromedial subdivision (VM neurons); axon collaterals of two neurons were not traced. Both groups of neurons sent terminal arbors into other nuclei of the lower brainstem. The DL neurons were distinguishable from the VM neurons in their receptive field (RF) location, neuronal position, somadendritic architecture, and projections to other brainstem nuclei. All neurons, except for two that were exclusively activated by noxious stimuli applied to the tongue, were responsive to light mechanical stimulation of peri- and intraoral structures. The RFs of the DL neurons were located in more posterior oral structures than those of the VM neurons. The RF of nearly all low-threshold DL neurons was located in the maxillary region, and that of the VM neurons, in contrast, involved the mandibular region. The VM neurons were located medial or ventral to the DL neurons. The soma size of the VM neurons was significantly larger than that of the DL neurons. Dendritic arbors of both groups could be separated into medial and lateral components. The ratio of the dendritic transverse areas in the medial vs. lateral component was significantly higher in the VM neurons than in the DL neurons. The DL neurons also issued collaterals that terminated in larger brainstem areas than those of the VM neurons. These observations provide new evidence on the morphological and functional properties of Vo neurons that contribute to reflex control of jaw and facial movements and modulation of sensory information.

Response properties of nociceptive and low‐threshold neurons in rat trigeminal pars caudalis

There is little doubt that trigeminal nociceptive neurons play a critical role in signaling the presence of harmful, or potentially harmful, orofacial stimuli. Unfortunately, there is only a limited understanding of how these neurons code such stimuli and whether this code is maintained in those structures responsible for generating overt reactions. The present series of experiments were designed to quantitatively document the response properties of nociceptive neurons in the rat trigeminal pars caudalis using the same electrical and innocuous and/or noxious mechanical and thermal stimuli employed in the characterization of nociceptive neurons with orofacial receptive fields in the rat superior colliculus. Neurons were classified as either low-threshold mechanoreceptive, wide-dynamic-range, or nociceptive-specific (type I, II) depending on their responsiveness to these stimuli. Nociceptive pars caudalis neurons (92/135, 68%) had receptive field organizations and input fibers (as indicated by latencies to electrical stimuli) quite different from those of low-threshold neurons (43/135, 32%). Nociceptive stimulus-response relationships for the population of wide-dynamic-range and nociceptive-specific type I neurons to contact heat stimuli were positively accelerating power functions with exponents of 3.9 and 4.4, respectively. This contrasted sharply with the low-threshold component of wide-dynamic-range neurons which was a negatively accelerating power function with an exponent of 0.7. All categories of nociceptive neurons also responded vigorously to cold stimuli. The thresholds of both hot and cold stimuli were often below psychophysical estimates of thermal pain, suggesting that "nociceptive" neurons process far more information than that required to signal potentially harmful stimuli. The fundamental similarities in nociceptive properties in pars caudalis and other structures of the central nervous system suggest that there is little transformation of the information encoded at successive levels of the neuraxis. This is consistent with the idea that the functional role of nociceptive neurons is reflected more in which circuits they are integrated and less in differences in their physiological properties.

Identification and characterization of rhythmic nociceptive and non-nociceptive spinal dorsal horn neurons in the rat

The properties of rhythmic low-threshold and multireceptive spinal dorsal horn neurons were determined. Multiple neuron recordings were made via a single electrode in the lumbar spinal cord of pentobarbital-anesthetized or decerebrate, unanesthetized, spinalized rats. The background activity of a total of 223 neurons was analysed: 21.0% of 176 fully characterized neurons were low threshold, 73.3% multireceptive and 5.7% nociceptive-specific neurons. Twenty of 100 neurons tested were driven by antidromic stimulation at the upper cervical cord. To identify and evaluate rhythmic harmonic oscillations in the discharges of spinal dorsal horn neurons during background activity and steady-state noxious heat-evoked responses, interspike interval, autocorrelation and autospectral analysis were performed. The background activity of 99 of the 223 neurons (44.4%) of our sample was rhythmic. The distribution of the fundamental spectral frequencies has a bimodal shape, the first band between 0.5 and 2 Hz and the second between 6 and 13 Hz. Low-threshold and multireceptive neurons had a similar incidence of rhythmicity (54.1 and 43.4%, respectively). Only one of 20 neurons with long ascending projections presented rhythmic background activity. Activation of heat-sensitive nociceptors within the cutaneous receptive fields of the neurons had a strong anti-rhythmic effect in nine of 15 (60%) neurons. No change was observed in the pattern of autospectra of non-rhythmic neurons or low-threshold neurons during noxious stimulation. Twenty-four of 37 (66.6%) rhythmic neurons retained their rhythmic background discharges during reversible cold-block spinalization at the upper thoracic cord. The incidence of neurons with burst-like discharges was highest among multireceptive neurons (98/129, 75.9%) and non-rhythmic neurons (89/124, 71.8%). Thus, rhythmicity exists in sensory neurons of the spinal dorsal horn probably generated within its local neuronal network and partially modulated by supraspinal descending systems. Rhythmicity is depressed by activity in primary afferent nociceptors. The role of rhythmicity for information transfer and neuronal plasticity is discussed.

Membrane properties of physiologically classified rat dorsal horn neurons in vitro: correlation with cutaneous sensory afferent input.

Dorsal horn neurons in the young rat spinal cord-hindlimb preparation were physiologically classified as wide dynamic range (WDR), nociceptive specific (NS) or low threshold (LT) according to their excitatory responses to low and high intensity mechanical stimuli applied to the hindlimb skin. Two additional types were classified: neurons displaying only sub-threshold excitations (SUB) and neurons displaying inhibitory events (INH), such as inhibitory post-synaptic potentials or interruption of spontaneous spiking following cutaneous stimulation. Direct intracellular current injection revealed four different patterns of spiking behaviour: group A neurons were characterized by tonic firing in response to depolarizing current pulses; group B neurons were strongly phasic, producing only one spike at the beginning of the pulse; group A-B neurons generated an early unsustained (< 300 ms) burst of spikes; and group C neurons exhibited anomalous rectification in response to hyperpolarizing current which was followed by a voltage-dependent rebound excitation. A statistically significant (P < or = 0.01) association existed between a neuron's physiological classification and its electrophysiological profile. The majority of WDR neurons responded with tonic firing and were assigned to group A, while NS neurons were strongly represented in group A-B. All INH neurons were assigned to group C. LT neurons were distributed between groups A and A-B, and SUB neurons were distributed between groups A and B. These data indicate, firstly, that dorsal horn neurons possess heterogeneous membrane properties and, secondly, that a relationship exists between a neuron's biophysical profile and its excitatory or inhibitory response to peripheral cutaneous afferent stimulation. The implications for dorsal horn somatosensory processing are discussed.

Physiological rationale for the treatment of neuropathic pain

Neuropathic pain occurs when irritation or injury of peripheral nerves causes the development of ectopic neural pacemaker sites and the degeneration of inhibitory interneurons. The type of neuropathic pain depends on the degree of nerve injury. Trigeminal nerve irritation only causes degeneration of some inhibitory interneurons leading to an excessive response of low-threshold mechanoceptive neurons to tactile stimulation and episodic, allodynic pain when the paroxysmal firing spreads to wide dynamic range neurons. Injury to the trigeminal nerve causes destruction of low-threshold mechanoceptive neurons and more extensive loss of inhibitory interneurons, leading to continuous overreaction of wide dynamic range neurons perceived as ongoing pain. Drugs that are GABA-B agonists and kainic acid antagonists should be effective in the treatment of episodic and allodynic pain, and drugs that are GABA-A agonists and NMDA antagonists should be useful in the treatment of ongoing neuropathic pain.

Thalamic VPM nucleus in the behaving monkey. II. Response to air-puff stimulation during discrimination and attention tasks

1. Single-unit activity was recorded in the ventral posterior medial (VPM) thalamic nucleus of awake monkeys while they performed detection and discrimination tasks involving tactile air-puff stimuli presented to the face. Neuronal responsiveness was compared directly with the monkey's discriminative performance. In addition, neuronal activity was compared when the monkey's attention was directed to the air-puff stimulus and when it was directed to a concurrent visual stimulus. 2. Neurons responding to the air-puff stimuli were classified as slowly adapting (SA), rapidly adapting (RA), inhibitory (IN), or multimodal (MM), according to their responses to manual and thermal stimulation, as well as their adaption rates to the air puff. Of 47 neurons responsive to air-puff stimulation and studied extensively in the behavioral task, 14 were classified as RA, 15 as SA, 6 as IN, and 12 as MM. The 12 MM neurons were so classified because, in addition to air puff, they responded to noxious heat, innocuous cooling, or noxious pinch. 3. Neurons from each class had restricted contralateral receptive fields localized within one division of the trigeminal nerve. There was no systematic difference in receptive-field size among groups. 4. A prominent difference in tactile responsiveness of MM neurons was response latency. Although the mean latency for RA, SA, and IN neurons was not significantly different (6.1, 9.1, and 12.2 ms, respectively), the mean latency for MM neurons was significantly longer than that for each of the other neuronal categories (28.8 ms; Ps < 0.001). These data suggest that the excitatory tactile afferent input to MM neurons is different from that to low-threshold neurons. 5. For RA, SA, and MM neurons the frequency of the neuronal discharge evoked by the air-puff stimulation was proportional to the intensity of the air puff. Thus responses of each neuronal class coded air-puff stimulus intensity. 6. The monkeys' ability to detect air-puff stimuli of various intensities was compared with the frequency of neuronal responses to those stimuli. Both the percent success in detecting differences in air-puff intensity and the detection latency were highly correlated with neuronal response frequency. The responses of all three excitatory neuronal categories corresponded well with the monkey's performance. Thus any or all of RA, SA, and MM neurons could play a role in the discrimination of air-puff intensities.(ABSTRACT TRUNCATED AT 400 WORDS)

Differential action of amitriptyline on neurons in the trigeminal nucleus

We studied the effect of amitriptyline (AMI) on neurons in the spinal trigeminal nucleus caudalis in cats anesthetized with alpha-chloralose. The IV injection of 1.0 to 4.0 mg/kg AMI had a differential effect on the inhibitory mechanisms controlling the responses of these neurons. AMI significantly enhanced the segmental inhibition (SI) of wide dynamic range (WDR) neurons but had little or no effect on low-threshold mechanoceptive neurons. AMI also facilitated the SI of some nociceptive specific (NS) neurons and the periventricular inhibition of some WDR and NS neurons, but these effects were not statistically significant. Our observations suggest that AMI exerts its antineuralgic effect by enhancing the ability of SI to prevent excessive firing of WDR neurons. This supports the notion that neuropathic pain is caused by dysfunction of inhibitory mechanisms in the CNS.

Involvement of bulbar respiratory and non-respiratory neurons in onset of expiration reflex

It was shown that excitation of high- and low-threshold superior laryngeal afferents triggers reflexes of varying complexity in a considerable proportion of non-respiratory neurons during experiments on cats anesthetized by Nembutal involving stimulation-induced expiration reflex. Systemic alterations in background firing activity were noted during this reflex in "respiratory" neurons; reflex reaction setting in as a result of low-threshold laryngeal afferent activation was also recorded in 22.4% of this group. Oligo- and polysynaptic excitatory connections were found between low-threshold laryngeal afferents and inspiratory beta neurons, P-cells, and laryngeal muscle motoneurons as opposed to inhibitory connections with inspiratory gammaneurons. This article discusses involvement of the neurons investigated in mechanisms of inspiratory inhibition, closure of the vocal chords, and adaptive decline in breathing rate occurring during expiration reflex.

Plasticity of some spinal dorsal horn neurons as revealed by pentobarbital-induced disinhibition

Extracellular activity was recorded from single spinal dorsal horn neurons in physiologically intact, awake, drug-free cats before and after the intravenous administration of 20 mg/kg pentobarbital (Pb). Pb produced a series of changes in response properties that reflect a significant moment-to-moment plasticity of some spinal dorsal horn neurons. Pb administration unmasked the ability of some low-threshold (LT) neurons to respond to noxious mechanical or thermal stimuli resulting in their being reclassified as wide dynamic range (WDR) neurons. Pb also appeared to unmask an afterdischarge in some neurons following noxious mechanical stimulation. In addition, some neurons appeared to be better able to signal changes in the intensity of mechanical stimulation after Pb. Neuronal receptive fields for low-threshold stimulation were reduced in many instances but enlargement was also observed. The responses of some neurons to peripheral stimulation were unchanged by Pb. We hypothesize that the relatively low doses of Pb used in the study reduced tonic inhibition of some spinal dorsal neurons although the observed effects could have been produced by excitation.

Excitatory amino acid receptors and nociceptive neurotransmission in rat spinal cord

Excitatory amino acid (EAA) receptor agonists were tested for their effect on identified rat spinal neurons. Only 75% of the spinal neurons tested increased their firing rate in response to iontophoretic application of one or more of the EAA receptor agonists, N-methyl-D-aspartate (NMDA), quisqualate (Quis), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid HBr (AMPA), and kainate (KA). NMDA and Quis or AMPA activated primarily nociceptive neurons (60% of these neurons were projection neurons) in the rat spinal cord. KA-activated neurons were primarily classified as low threshold neurons. Both NMDA and AMPA, at subthreshold doses, significantly increased neuronal responses to peripheral noxious mechanical stimulation; NMDA also significantly increased neuronal responses to peripheral noxious thermal stimulation. Iontophoretically applied phencyclidine (PCP) decreased NMDA-induced firing in 100% of the cells tested while Quis-induced firing was blocked by PCP in only 33% of the cells tested. The reported analgesic effects of PCP in humans may result from a spinal action involving its well documented interaction with NMDA receptors.

Effect of electroacupuncture of neuronal responses of the cat oral trigeminal nucleus during nociceptive and non-nociceptive stimulation

UDC 615.844.4.015.4:612.822].076.9 Interest in the oral trigeminal nucleus (OTN) in connection with the study of pain has increased considerably after the discovery of a well-marked focus of evoked activity in it during nociceptive stimulation of the orofacial receptive fields. The so-called dual representation of pain in the trigeminal complex [2] called for a close study of all features of the organization of the various nuclei of this concept (the oral, in particular), which could be responsible for their specific role in the conduction of nociceptive and non-nociceptive signals in the CNS. Despite several investigations of the organization of the afferent input and neuronal responses of OTN, only a few investigators [4] have attempted to study this problem from the standpoint of discovery of different functional types of neurons, involved in the conduction of nociceptive and non-nociceptive signals, as has been done in relation to the caudal trigeminal nucleus [8]. From this point of view it is interesting to study the character of the effect of electroacupuncture (EAP), an effective modulator of nociceptive signals. The aim of this investigation was to study the effect of EAP on responses of neurons of different functional types in OTN to noceptive and non-nociceptive stimulation. EXPERIMENTAL METHOD Acute experiments were carried out on eight adult cats weighing 2.5-4 kg. The dissection was carried out under hexobarbital anesthesia (15 mg/kg, intraperitoneall y), and the animals were subsequently immobilized with suxamethonium and artificially ventilated. Unit activity was recorded extracellularly by glass microelecrodes with a tip 1-3 ~ in diameter, filled with 2 M KCI solution, and with a resistance of 4-10 M~, with the aid of a YC-10 electrophysiological complex ("Nihon Kohden," Japan). Pulsation of the brain was prevented by flooding its surface with agar-agar. Stimulation of the dental pulp and of the lip with square pulses, i and 0.i msec respectively in duration and with a strength of 0-50 mA, by means of an ESU-2 stimulator was used as testing stimulation. The nociceptive character of afferent stimulation of a particular intensity was determined by preliminary study of the thresholds of onset of non-nociceptive and nociceptive behavioral responses of the animals to both types of stimulation. Depending on the character of their response to electrical stimulation of the dental pulp and lip, the neurons were divided into three groups. Neurons of group i responded to weak stimulation and their response was unchanged when the strength of stimulation was increased. They were regarded as non-nociceptive low-threshold neurons (LT neurons). Neurons of the second group also began to respond to weak stimulation of lip or dental pulp, but the neuron discharged more strongly when its intensity was increased. Such neurons were classed as neurons with wide dynamic range (WDR neurons). Finally, neurons of the third group responded only to intensive stimulation of the dental pulp and lip, and they were accordingly characterized as specific nociceptors (SN neurons). EAP was applied through steel needles, inserted into the lower part of the base of the concha auriculae. The duration of the pulses was 1.2 msec, their frequency i Hz, their intensity about I0 mA, and stimulation lasted for 5-i0 rain. Research Institute of Reflex Therapy, Moscow. (Presented by Academician of the Academy

Nociceptive neurons in rat superior colliculus: response properties, topography, and functional implications.

1. Extracellular recordings were made from single superior colliculus neurons in urethane-anesthetized rats in response to mechanical and/or thermal stimulation of the skin. In addition to those activated by low-threshold (LT) tactile stimuli, many neurons responded preferentially, or solely, to noxious stimuli. Two functionally defined subtypes of nociceptive neurons were distinguished: wide-dynamic-range (WDR) neurons, which responded optimally to noxious stimuli but also to innocuous stimuli; and nociceptive-specific (NS) neurons, which responded solely to frankly noxious stimuli. The thermal thresholds were 42-45 degrees C, and the stimulus-response relationships were positively accelerating power functions with exponents of 2.9 (WDR) and 3.1 (NS). 2. WDR neurons also responded to cooling of the skin to temperatures below 24 degrees C. Like noxious heat responses, cold responses were monotonically graded as the intensity of the cold stimulus was increased. Thus the temperature sensitivity of thermal-sensitive neurons in the superior colliculus appeared to be tuned to detect large deviations from ambient skin temperature in either direction once threshold is reached. 3. LT neurons were somatotopically organized, with the head and forelimbs rostral and the trunk and hindlimbs caudal. The limbs were generally represented further lateral in the structure, whereas more proximal body parts were more medial. Nevertheless, there was extensive overlap of body parts especially in areas of transition. Thus, a "block-to-block" or "area-to-area" rather than a "point-to-point" representation of the body surface was evident. 4. The nociceptive representation did not violate the general LT somatotopy but neither was it coextensive. Virtually all nociceptive neurons had trigeminal receptive fields and were thus heavily represented in the rostral superior colliculus, where the LT face representation was also located. No nociceptive neurons were present in the caudal one-third of the structure. A general dorsal-to-ventral segregation of somatosensory neurons also was noted, so that in a given electrode penetration, LT neurons usually were the most superficial, WDR neurons were just below these, and NS neurons were deepest of all. 5. The presence of overlapping LT and nociceptive trigeminal representations in the superior colliculus seems particularly adaptive in view of the fact that rodents use their vibrissae for exploring their environment and thus put rostral body parts at risk during such behaviors.(ABSTRACT TRUNCATED AT 400 WORDS)

I. Spinal recordings suggest that wide-dynamic-range neurons mediate sympathetically maintained pain

In order to determine which classes of spinal neurons are capable of mediating sympathetically maintained pain, recordings were made from single somatosensory neurons in spinal cords of anesthetized cats. Each neuron was functionally identified with mechanical stimuli, and its responses to electrical stimulation of the sympathetic trunk were recorded. Nearly half (45%) of the wide-dynamic-range (WDR) neurons tested were activated by sympathetic stimulation, but none of the high threshold (nociceptor-specific) neurons and only 17% of the low threshold neurons were activated. Sympathetic activation was most common for WDR neurons that had the following: receptive fields proximal to the toes, low thresholds for mechanical activation, and both rapidly and slowly adapting responses to pressure. The predominant WDR response to sympathetic stimulation was long latency (>1 sec) excitation. Sympathetic activation of WDR neurons was abolished by each of the following procedures: subcutaneous injection of local anesthetic, cooling of the receptive field with ice, and intravenous injection of the alpha-adrenergic blocker, phentolamine. The axons of some sympathetically activated WDR were shown to project to higher centers. These results indicate that WDR neurons are the only spinal nociceptive neurons activated by sympathetic efferent activity in this preparation. Therefore, WDR neurons, rather than high threshold neurons, are most likely to mediate the spinal component of sympathetically maintained pain. These results provide supporting evidence for our previous hypothesis [30] that sympathetically maintained pain is mediated by myelinated mechanoreceptors acting on sensitized WDR neurons. Our results also demonstrate that sympathetic activation of WDR neurons is mediated by an alpha-adrenergic mechanism in the skin.

Primate nucleus gracilis neurons: responses to innocuous and noxious stimuli.

1. Recordings were made from 67 neurons in the nucleus gracilis (NG) of anesthetized macaque monkeys. All of the cells were activated antidromically from the ventral posterior lateral (VPL) nucleus of the contralateral thalamus. Stimuli used to activate the cells orthodromically were graded innocuous and noxious mechanical stimuli, including sinusoidal vibration and thermal pulses. 2. The latencies of antidromic action potentials following stimulation in the VPL nucleus were significantly shorter for cells in the caudal compared with the rostral NG. The mean minimum afferent conduction velocity of the afferent conduction velocity of the afferent fibers exciting the NG cells was 52 m/s, as judged from the latencies of the cells to orthodromic volleys evoked by electrical stimulation of peripheral nerves. The overall conduction velocity of the pathway from peripheral nerve to thalamus was approximately 40 m/s. 3. Cutaneous receptive fields on the distal hindlimb usually occupied an area equivalent to much less than a single digit. However, a few cells had receptive fields up to or exceeding the area of the foot. 4. NG cells were classified by their responses to graded mechanical stimulation of the skin as low threshold (LT) or wide dynamic range (WDR). No high-threshold NG cells were found. A special subcategory of pressure-sensitive LT (SA) neurons was recognized. Many of these cells were maximally responsive to maintained indentation of the skin. The sample of NG cells differed from the population of primate spinothalamic and spinocervicothalamic pathways so far examined, in having a larger proportion of LT neurons and a smaller proportion of WDR cells. A few NG cells responded best to manipulation of subcutaneous tissue. 5. Discriminant analysis permitted the NG cells to be assigned to classes determined by a k-means cluster analysis of the responses of a reference set of 318 primate spinothalamic tract (STT) cells. There were four classes of cells based on normalized responses of individual neurons and another four classes based upon responses compared across the population of cells. The NG cells were allocated to the various categories in different proportions than either primate STT cells or spinocervicothalamic neurons, consistent with the view that the functional roles of these somatosensory pathways differ. 6. Some of the pressure-sensitive NG cells were excited when the skin was stretched, suggesting an input from type II slowly adapting (Ruffini) mechanoreceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Mechanical response properties of ventroposterior medial thalamic neurons in the alert monkey.

The properties of trigeminal cutaneous thalamic neurons were explored in alert cynomolgous monkeys to determine receptive field and response characteristics. Two monkeys received juice reward for sitting quietly while an investigator probed the monkey's face with mechanical stimuli. Extracellular single unit recordings were made from the ventroposterior medial thalamic nucleus (VPM), and mechanical response properties were evaluated for each cell having an extraoral cutaneous receptive field. Of 89 cells examined, 90% responded best to innocuous tactile stimulation, and were classified as low threshold. The other 10%, classified as wide dynamic range, showed a graded response to increasingly intense stimuli, with a maximum discharge to noxious pinch. Of the low threshold neurons, most exhibited excitatory responses, with about half being rapidly adapting and the others slowly adapting. The spontaneous activity of 11% of the low threshold neurons was inhibited by stimulation of the neuron's receptive field. There was no systematic difference in receptive field size for the various types of neurons, but the receptive fields of wide dynamic range cells were smaller than those previously observed in trigeminopthalamic neurons of the medullary dorsal horn. The wide dynamic range and inhibitory low threshold neurons were located primarily in the caudal third of VPM, while the excitatory low threshold neurons were located throughout. In summary, response characteristics of VPM neurons show more diversity in the alert monkey than has been reported in paralyzed and/or anesthetized animals.