The effects of a distant noxious stimulation on A and C fibre-evoked flexion reflexes and neuronal activity in the dorsal horn of the rat

In the halothane-anaesthetized rat, the responses of 49 neurons in the lumbo-sacral cord and the reflex discharge in the common peroneal nerve following electrical stimulation of the sural nerve were recorded in order to study possible relations between neuronal events and reflex nerve discharges. A distant noxious stimulus (to activate Diffuse Noxious Inhibitory Controls (DNIC) of Le Bars et al.¹⁹) was used as a conditioning stimulus. Only the responses of neurons receiving an input from both A and C fibres were studied. The neurons were classified as class 1 (low threshold mechanoreceptive input only, n = 2), class 2 (nonnoxious and noxious inputs, n =34) or class 3 (responding to noxious stimuli only, n = 13). During conditioning stimulation the C fibre evoked discharge was inhibited in 32 out of 34 class 2 neurons. The A fibre-evoked discharge was simultaneously inhibited in 29 of these neurons. The main effect of the distant noxious stimulation on the C fibre evoked neuronal discharge was to decrease the discharge by a constant number of spikes, independent of the level of evoked activity. Only one class 3 neuron was inhibited during conditioning stimulation and none of the class 1 cells were influenced by DNIC. During conditioning stimulation the late and prolonged C fibre evoked reflex nerve discharge (latency 160–200 ms, duration up to several hundred ms) was strongly depressed. Concomitantly, a short-lasting reflex nerve discharge appeared over the interval 115–160 ms. This released reflex nerve discharge (RR) had a constant latency. There was no simultaneous change of the Aβ evoked reflex nerve discharge. After the end of the distant noxious stimulation the late C fibre evoked reflex nerve discharge (latency 160–200 ms) recovered. Concomitantly, the RR disappeared. The possibility that the class 2 neurons and the class 3 neurons are intercalated in different reflex pathways is discussed.     

Differential Effects of a Distant Noxious Stimulus on Hindlimb Nociceptive Withdrawal Reflexes in the Rat

Recent studies indicate that the nociceptive withdrawal reflexes to individual muscles are evoked by separate reflex pathways. The present study examines whether nociceptive withdrawal reflexes to different muscles are subject to differential supraspinal control in rats. A distant noxious stimulus was used to activate a bulbospinal system which selectively inhibits 'multireceptive' neurons (i.e. neurons receiving excitatory tactile and nociceptive inputs) in the dorsal horn of the spinal cord. Withdrawal reflexes, recorded with electromyographic techniques in single hindlimb muscles, were evoked by standardized noxious pinch. Thirty-seven rats, anaesthetized with halothane and nitrous oxide, were used. Whereas withdrawal reflexes to the extensor digitorum longus and brevis, tibialis anterior and biceps posterior muscles were strongly inhibited, reflexes to interossei muscles were potentiated during noxious pinch of the nose. Reflexes to peronei muscles were not significantly changed. The effects on the reflexes usually had an onset latency of <0.5 s and outlasted the conditioning stimulation by up to 2 s. The monosynaptic la reflex to the deep peroneal nerve, innervating dorsiflexors of the digits and ankle, was not significantly changed during noxious pinch of the nose. Hence, the inhibitory effects on the hindlimb withdrawal reflexes induced by the conditioning stimulation were presumably exerted on reflex interneurons. It is concluded that nociceptive withdrawal reflexes to different hindlimb muscles are differentially controlled by descending pathways activated by a distant noxious stimulus. The results support our previous conclusion that there are separate nociceptive withdrawal reflex pathways to different hindlimb muscles.     

Discharge characteristics of sympathetic efferents to the knee joint of the cat

Sympathetic postganglionic neurons to the knee joint of the cat were studied to characterize the nerve supply and response to somatic stimulation. In halothane anesthetized cats, the sympathetic postganglionic units from a branch of medial articular nerve (MAN) were dissected. The other branch of MAN was left intact. Most of the central filaments of MAN showed spontaneous discharge. The frequency of the spontaneous discharge of single units ranged from 0.2 to 2.9 impulses per second. Cardiovascular rhythmic modulation was observed in most of the filaments tested. Phenylephrine-induced baroreceptor stimulation caused inhibition of the discharges. Repetitive stimulation of the lumbar sympathetic trunk or the peripheral cut end of MAN led to a decrease in the local temperature inside the joint. The frequency threshold for decreasing the temperature of the joint was approximately 1 Hz. Maximum effects were obtained with 5 Hz stimulation. Histograms of MAN sympathetic efferent fibre activity following electrical stimulation of afferent nerve fibres in the MAN exhibited two response periods. The first, of about 280 ms latency, was elicited by myelinated fibre excitation (the A-reflex) and the second, with a latency of approximately 700 ms, was evoked by unmyelinated fibre excitation (the C-reflex). Electrical stimulation of radial afferent nerve produced similar A- and C-reflex discharges in sympathetic fibres of MAN. Passive movement of the knee joint within its normal working range (flexion, extension or outward rotation) had very little effect on sympathetic efferent nerve activity in MAN, whereas noxious outward rotation of the joint produced a reflex increase in activity to about 140% of the prestimulus control level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Responses of cardiac vagus and sympathetic nerves to excitation of somatic and visceral nerves

Somato-vagal and somato-sympathetic reflex responses were studied by recording simultaneously the activity of cardiac vagal and sympathetic efferents following excitation of various somatic (and 1 visceral) nerves in chloralose-anesthetized dogs.Stimulation of pure cutaneous (infraorbital, superficial radial, sural nerves), muscle (gastrocnemius, hamstring nerves) and mixed nerves (sciatic, brachial, intercostal, spinal) with short trains of pulses inhibited the activity of cardiac vagus nerve and excited that of cardiac sympathetic nerve after a latency of approximately 40–60 ms, depending on the nerve stimulated. These responses were followed by the opposite response, i.e. excitation of vagus and long-lasting inhibition (`silent period') of sympathetic nerve activity. These biphasic reflex responses recorded from both autonomic nerves had similar latencies so that a clear reciprocal relationship was observed. In addition to the above reflex responses which were observed in most instances, two peaks of excitation of short duration were recorded from the vagus nerve, in some instances, and an ‘early (spinal) reflex’ in sympathetic nerve was also observed. Both excitatory and inhibitory responses described above in either nerve were readily evoked by excitation of Group II (Aβ), but not Group I (Aα), afferent fibers and increased in magnitude when Group III (Aδ) afferents were also excited. Group IV (C) afferent contributed insignificantly to the somato-vagal reflex. The vagus nerve discharge evoked by sinus nerve stimulation was inhibited during reflex inhibition produced by somatic nerve stimulation. The latency of such inhibition was less than 20 ms and lasted for 100 ms after sural nerve stimulation. We conclude that, as in case of the baroreceptor reflex and autonomic component of the ‘defense reaction’, the somato-vagal and somato-sympathetic reflex responses are reciprocal in nature.     

Electrophysiological analysis of the ascending and descending components of the micturition reflex pathway in the rat

Electrophysiological techniques were used to examine the organization of the spinobulbospinal micturition reflex pathway in the rat. Electrical stimulation of afferent axons in the pelvic nerve evoked a long latency (136 +/- 41 ms) response on bladder postganglionic nerves, whereas stimulation in the dorsal pontine tegmentum elicited shorter latency firing (72 +/- 25 ms) on these nerves. Transection of the pelvic nerve eliminated these responses. Firing on the bladder postganglionic nerves was evoked by stimulation in a relatively limited area of the pons within and close to the laterodorsal tegmental nucleus (LDT) and adjacent ventral periaqueductal gray. Stimulation at sites ventral to this excitatory area inhibited at latencies of 107 +/- 11 ms the asynchronous firing on the bladder postganglionic nerves elicited by bladder distension. Electrical stimulation of afferents in the pelvic nerve evoked short latency (13 +/- 3 ms) negative field potentials in the dorsal part of the periaqueductal gray as well as long latency (42 +/- 7 ms) field potentials in and adjacent to the LDT. The responses were not altered by neuromuscular blockade. Similar responses were elicited by stimulation of afferent axons in the bladder nerves. The sum of the latencies of the ascending and descending pathways between the LDT and the pelvic nerve (i.e. 72 ms plus 42 ms = 114 ms) is comparable although somewhat shorter (22 ms) than the latency of the entire micturition reflex. These results provide further evidence that the micturition reflex in the rat is mediated by a spinobulbospinal pathway which passes through the dorsal pontine tegmentum, and that neurons in the periaqueductal gray as well as the LDT may play as important role in the regulation of the micturition.     

Long-lasting neuronal activity in rat dorsal horn evoked by impulses in cutaneous C fibres during noxious mechanical stimulation

The responses of 44 nociceptive neurones in the lumbar dorsal horn evoked by controlled mechanical stimulation of the skin, with or without conduction block in myelinated afferent fibres, were studied in the halothane-anaesthetized rat, in order to evaluate the effects of impulses in cutaneous nociceptive C fibres on dorsal horn neurones. Continuous non-noxious pinch of the skin evoked a short-latency discharge (mean latency 15 ms) in all the 13 class 2 neurones (i.e. neurones responding to both non-noxious and noxious stimulation of the skin) tested. The short-latency discharge was followed by weak prolonged activity in 6 neurones. Following noxious pinch of the skin a prominent late discharge (peak latency 150 ms-2 s) was evoked, which in all but two class 2 neurones outlasted the stimulation period (5-10 s). The discharge evoked by noxious pinch in class 3 neurones (i.e. neurones responding to noxious stimulation only) did not usually outlast the stimulation period. In all but two nociceptive neurones tested (n = 26) the late activity evoked by noxious pinch remained, albeit at a lower frequency in some neurones, during a conduction block in A fibres2,3. Hence this late discharge is probably mainly generated by impulses in nociceptive C fibers. It is concluded that nociceptive C fibres have an important role in sustaining long-lasting activation of class 2 neurones during noxious stimulation of the skin and that long-lasting discharges in these neurones indicates tissue damage to their receptive fields.     

Differential inhibition produced by peripheral conditioning stimulation on noxious mechanical and thermal responses of different classes of spinal neurons in the cat

The effect of conditioning stimulation of a peripheral nerve on responses of spinal neurons (dorsal horn cells and motoneurons) was studied in 16 decerebrate-spinal cats. The activity of dorsal horn cells was recorded with a microelectrode at the lumbosacral spinal cord and the single-unit activity of motoneurons was recorded from a filament of ventral rootlet divided from either the L7 or S1 ventral root. The responses of spinal neurons were evoked by noxious and innocuous mechanical stimuli and by noxious thermal stimuli applied to the receptive fields. The peripheral conditioning stimulation was applied to the tibial nerve with repetitive electrical pulses (2 Hz) at an intensity either suprathreshold for A delta or C fibers for 5 min. Applying conditioning stimulation to a peripheral nerve produced a powerful inhibition of the responses elicited by noxious stimuli, suggesting this inhibition is an antinociceptive effect. The inhibition produced by peripheral conditioning stimulation was differentially greater on the responses to noxious than to innocuous stimuli. Based on the results obtained from conditioning stimulation with graded strengths, afferent inputs from both myelinated and unmyelinated fibers seem to contribute to the production of the antinociceptive effect. The magnitude of the antinociceptive effect is bigger for the responses to noxious thermal than to mechanical stimuli. Furthermore, the reflex activity recorded in motor axons seemed to be more sensitive than in dorsal horn cells to the antinociceptive effect.     

The digastric reflex evoked by tooth-pulp stimulation in the cat and its modulation by stimuli applied to the limbs

The digastric reflex evoked by electrical stimulation of tooth pulp in anaesthetized cats was studied together with the effects on this reflex of stimulating other parts of the body.The threshold for the digastric reflex generally lay in the range of stimulus intensities which would excite a large proportion of the pulpal afferent fibres which suggested that a large amount of central summation was required to evoke the reflex. During the course of 2527 experiments, the threshold for the reflex increased. It was also found that repeated application of suprathreshold stimuli produced first an increase and then a decrease in the reflex response.The application of noxious but not of non-noxious mechanical conditioning stimuli to the limbs produced strong, long-lasting depressions of the digastric reflex. Electrical conditioning stimuli applied to the limbs also depressed the reflex; this depression had a latency of onset of 20–50 ms and lasted for up to 500 ms. When conditioning stimuli were applied to the saphenous nerve, the depression of the reflex occurred only when the stimuli were of an intensity sufficient to excite fibres conducting at less than 40 m·s⁻¹; it may be assumed that some of these fibres would have been high threshold mechanoreceptors or nociceptors. These results show that noxious stimulation of anatomically remote structures can depress the activity of a population of trigeminal brainstem neurones.The opiate antagonist, naloxone, had no detectable effect on either the digastric reflex or the depression of the reflex produced by stimulating other parts of the body. The serotonin antagonists, methysergide and cinanserin, strongly depressed the digastric reflex but it was not clear whether these drugs also affected the depression of the reflex by the conditioning stimuli.     

Heterotopic painful stimulation decreases the late component of somatosensory evoked potentials induced by electrical tooth stimulation

The purpose of this study was to determine the relationship between the late component of somatosensory evoked potentials (SEP) induced by electrical tooth stimulation and subjective pain estimation when heterotopically painful stimulation was delivered to humans. The noxious electrical conditioning stimuli were applied to the left median nerve in noxious session I and the right median nerve in noxious session II for 10 min. The amplitude of the late component and visual analogue scale (VAS) value were both decreased significantly by conditioning stimuli in both sessions. The maximum decreases in SEP amplitude and VAS value induced by conditioning stimuli were respectively 40.2 and 37.2% in noxious session I and 49.3 and 42.3% in noxious session II. After-effect was observed 5 min after removal of the conditioning stimuli. The rates of decrease were thus nearly the same and independent of the site of conditioning stimulation in noxious sessions I and II. The SEP amplitude was significantly correlated with VAS values. The present study revealed that SEP amplitude and subjective pain intensity estimated by VAS following electrical tooth stimulation can be decreased by noxious stimuli to hand. This finding that heterotopic painful stimulation attenuates experimentally-induced tooth pain suggests a triggering of diffuse noxious inhibitory control (DNIC) with after-effect in trigeminal region.     

Modulation of upper extremity motor evoked potentials by cutaneous afferents in humans.

The excitability of motoneurons controlling upper limb muscles in humans may vary with cutaneous nerve stimulation. We investigated the effect of noxious and non-noxious conditioning stimuli applied to right and left digit II and right digit V on motor evoked potentials (MEPs) recorded from right thenar eminence, abductor digiti minimi, biceps and triceps brachii muscles in twelve healthy subjects. Transcranial magnetic stimulation (TMS) was applied at interstimulus intervals (ISI) ranging from 40 to 160 ms following conditioning distal digital stimulation. TMS and transcranial electrical stimulation (TES) were compared at ISI 80 ms. Painful digital stimulation caused differential MEP amplitude modulation with an early maximum inhibition in hand muscles and triceps brachii followed by a maximum facilitation in arm muscles. Stimulation of different digits elicited a similar pattern of MEP modulation, which largely paralleled the behavior of cutaneous silent periods in the same muscles. Contralateral digital stimulation was less effective. MEPs following TMS and TES did not differ in their response to noxious digital stimulation. MEP latencies were shortened by cutaneous stimuli. The observed effects were stimulus intensity dependent. We conclude that activation of A-alpha and A-delta fibers gives rise to complex modulatory effects on upper limb motoneuron pools. A-delta fibers initiate a spinal reflex resulting in MEP amplitude reduction in muscles involved in reaching and grasping, and MEP amplitude facilitation in muscles involved in withdrawal. These findings suggest a protective reflex mediated by A-delta fibers that protects the hand from harm. A-alpha fibers induce MEP latency shortening possibly via a transcortical excitatory loop.     

Cortical motor neuron excitability during cutaneous silent period

Objective: To investigate cortical motor neuron excitability during cutaneous silent period (CSP), motor evoked potentials (MEPs) from abductor pollicis brevis following transcranial magnetic stimulation (TCM) were recorded with and without a conditioning of ipsilateral painful digital nerve electric stimulation.Methods: MEPs following TCM were recorded with and without a conditioning stimulation at an interstimulus interval (ISI) from 0 ms to 100ms in 6 controls and four patients who had reduced pain sensation in unilateral upper limbs associated with cervical syringomyelia. In addition MEPs and evoked spinal cord potentials (ESCPs) from cervical epidural space following TCM with and without a conditioning stimulation were recorded in four patients with thoracic myelopathy.Results: MEP amplitude was clearly attenuated by a conditioning stimulation at an ISI from 40 ms to 80 ms in controls (statistically significant at 60 ms). In patients with cervical syringomyelia, MEP amplitude was attenuated by a conditioning stimulation in asymptomatic hands similarly in controls but that was unchanged by a conditioning stimulation in the symptomatic hand with reduced pain sensation. In patients with thoracic myelopathy MEP amplitude was attenuated by conditioning stimulation similarly in controls, but ESCP amplitude was unchanged.Conclusions: We demonstrated that noxious cutaneous nerve stimulation suppressed spinal motor neurons but cortical motor neuron excitability was unchanged during CSP. In clinical practice, measurement of MEP suppression after noxious cutaneous nerve stimulation may provide useful information in patients with damaged pain related nerve fibers.     

Diffuse noxious inhibitory controls (DNIC) in the rat with or without pCPA pretreatment

Diffuse Noxious Inhibitory Controls (DNIC) were investigated in anaesthetized intact rats, with or without p-chlorophenylalanin (pCPA) pretreatment. Dorsal horn convergent neurones responding to both noxious and non-noxious stimuli applied to their excitatory receptive field located on the distal part of the hindlimb, were recorded in the lumbar spinal cord. These cells received Aα and C fibre inputs as shown by electrical stimulation of their receptive field.In control animals, the evoked responses to C fibre inputs coulb be strongly inhibited by various noxious stimuli applied to widespread areas of the body: the inhibitory effects induced by intraperitoneal administration of bradykinin, pinch applied to the tail or muzzle and noxious heat applied to the tail were of 77%, 87%, 83% and 61% respectively. Long-lasting post-effects were seen in most cases after cessation of the application of the conditioning stimulus.Pretreatment with pCPA (300 mg/kg, i.p., 3 days) resulted in a strong reduction of DNIC. The inhibitory effects induced by intraperitoneal administration of bradykinin, pinch applied to the tail or muzzle and noxious heat applied to the tail were reduced by 47%, 63%, 87% and 63%, respectively. The post-effects were also reduced both in terms of magnitude and duration.These results strongly suggest that serotonergic pathways are partially involved in     

Neural organization of the viscero-cardiac reflexes

The reflex responses evoked in the postganglionic nerves to the heart were tested in chloralose-anaesthetized cats. Electrical stimulation of the A delta afferent fibres from the left inferior cardiac nerve evoked spinal and supraspinal reflex responses with the onset latencies of 36 ms and 77 ms respectively. The most effective stimulus was a train of 3-4 electrical pulses with the intratrain frequency of 200-300 Hz. Electrical stimulation of the high threshold afferent fibres (C-fibres) from the left inferior cardiac nerve evoked the reflex response with the onset latency of 200 ms. The C-reflex was present in intact animals and disappeared after spinalization. The most effective stimulus to evoke this reflex was a train of electrical pulses delivered at a frequency of 1-2 Hz with an intratrain frequency of 20-30 Hz. The most prominent property of the C-reflex was its marked increase after prolonged repeated electrical stimulation. We conclude that: (1) viscero-cardiac sympathetic reflexes may be organized at the spinal and supraspinal level; (2) viscero-cardiac sympathetic reflexes evoked by stimulation of the A delta and C afferent fibres from the left inferior cardiac nerve have different central organization.     

Differential labeling of the vestibular complex following unilateral injections of horseradish peroxidase into the cat and rat locus coeruleus

In anaesthetized cats, lumbar dorsal horn neurons were excited by brief noxious radiant heating of glabrous hindpaw skin. These nociceptive responses were inhibited by concomitant repetitive electrical stimulation of the ipsilateral deep radial nerve. Noxious heat responses were linearly correlated with skin temperature during heating. The slope of this stimulus-response function was decreased, and the response threshold increased, by deep radial nerve stimulation. Microinjection of lidocaine into the medullary raphe attenuated the inhibition induced by deep radial nerve stimulation. The results indicate that in the cat, ‘diffuse noxious inhibitory controls’ (DNIC) involve medial medullary regions.     

Analysis of reflex activity in cardiac sympathetic nerve induced by myelinated phrenic nerve afferents

Electrical stimulation of the phrenic nerve afferents evoked excitatory responses in the right inferior cardiac sympathetic nerve in chloralose-anaesthetized cats. The reflex was recorded in intact and spinal cats. The latency and threshold of the volley recorded from the phrenic nerve as well as of the cord dorsum potentials evoked by electrical stimulation of the phrenic nerve indicated that group III afferents were responsible for this reflex. The phrenicocardiac sympathetic reflex recorded in intact cats was followed by a silent period. The maximum amplitude of the reflex discharges was 800 microV, the latency was 83 ms and the central transmission time 53 ms. Duration of the silent period lasted up to 0.83 s. In spinal cats the reflex was recorded 5.5-8 h after spinalization. The maximum amplitude of the spinal reflex discharges ranged from 22 to 91 microV and the latency from 36 to 66 ms.     

The nictitating membrane response: An electrophysiological study of the abducens nerve and nucleus and the accessory abducens nucleus in rabbit

The nictitating membrane response to periocular electrostimulation was investigated in anesthetized and paralyzed rabbits. Recordings from the abducens nerve, which carries the fibers innervating retractor bulbi muscles that are primarily involved in this reflex, showed two distinct volleys to effective stimulation: a short duration volley with a minimum latency of approximately 4 ms and a longer duration volley beginning approximately 10 ms after stimulus onset and lasting up to 25 ms. Recordings of antidromically evoked field potentials via microelectrodes indicated large responses to abducens nerve stimulation in the vicinity of the accessory abducens nucleus. Single unit recordings from the accessory abducens nucleus produced spike trains with minimal latencies of 3.7–5 ms to eyeshock. The latency of spike discharge was inversely related to stimulus current. Units in the abducens nucleus did not show stimulus-elicited spiking, suggesting that the accessory abducens, but not the abducens, is primarily involved in the reflex pathway. Transverse knife cuts which separated caudal areas of the sensory trigeminal complex from the accessory abducens nucleus did not attenuate the efferent volley to suprathreshold stimulation, suggesting that more rostral components of the trigeminal complex are primarily involved in the reflex pathway.     

Diffuse noxious inhibitory controls of lumbar spinal neurons involve a supraspinal loop in the cat

In anaesthetized cats, lumbar dorsal horn neurons were excited by brief noxious radiant heating of glabrous hindpaw skin. These nociceptive responses were inhibited by concomitant repetitive electrical stimulation of the ipsilateral deep radial nerve. Noxious heat responses were linearly correlated with skin temperature during heating. The slope of this stimulus-response function was decreased, and the response threshold increased, by deep radial nerve stimulation. Microinjection of lidocaine into the medullary raphe attenuated the inhibition induced by deep radial nerve stimulation. The results indicate that in the cat, ‘diffuse noxious inhibitory controls’ (DNIC) involve medial medullary regions.     

Effect of stimulation of the central gray matter of the midbrain on responses of neurons of the ventroposteromedial nucleus of the thalamus in cats

Effect of the midbrain central gray matter (CGM) stimulation on neuronal responses of the thalamic ventro-postero-medial (VPM) nucleus evoked by stimulation of the tooth pulp, A-alpha, A-delta fibres of the infraorbital nerve and caudal nucleus of the spinal trigeminal tract have been studied in cats under thiopental-chloralose anesthesia. It is shown that the CGM stimulation by a short train of stimuli evoked excitatory responses with a latency of 30 ms in part of investigated neurons. The conditioning CGM stimulation suppressed responses in neurons of "low-threshold", "convergent" and "high-threshold" groups. Responses induced by stimulation of the tooth pulp and A-delta fibres of the infraorbital nerve in 40% of neurons and by stimulation of the A-alpha fibres of the infraorbital nerve in about 26% of investigated thalamic neurons were completely suppressed. The inhibitory influence of the CGM stimulation on neuronal responses evoked by stimulation of peripheral nerves and caudal nucleus of the spinal trigeminal tract shows that the CGM influences directly the activity of thalamic neurons.     

Bulbar influences on the periaqueductal gray. Potential role in nociception

Unit activity was recorded from 96 neurons in the periaqueductal gray (PAG) in response to focal electrical stimulation of the lateral reticular nucleus (LRN) and the nucleus gigantocellularis (NGC), in anesthetized, curarized rats. Consistent with anatomical studies showing direct projections from these nuclei to PAG, short latency excitatory responses (less than 5 ms) were found in 63 neurons and inhibition of the activity in 28 neurons. Peripheral noxious heat stimulation was effective in altering the activity in 36 of these neurons (38%). The LRN and NGC stimuli inhibited the noxious evoked responses in 26 of these neurons. The inhibition could also be induced when the dorsolateral funiculi (DLFs) were cut. These results indicate that LRN and NGC can have a direct influence on PAG neurons, which are probably involved in the processing of noxious information.