Intense peripheral electrical stimulation evokes brief and persistent inhibition of the nociceptive tail withdrawal reflex in the rat

In a study of modulation of nociception by sensory inputs, electrical stimulation was applied to specific sites in the hindlimb and effects on the nociceptive tail withdrawal reflex were monitored in the lightly anaesthetized rat. Stimulation was applied to previously defined sites in the hindlimb, meridian points femur-futu (ST-32), fengshi (GB-31) and zusanli (ST-36). It consisted of a 4 Hz train of 2 ms square pulses given for 20 min at 20 × the threshold intensity required for muscle twitch. Tail withdrawal was provoked by application of a noxious heat stimulus applied to the tip of the tail. Results were expressed as a percentage of the maximal possible inhibition which is achieved when the post-treatment latency is 2 × the pre-treatment latency otherwise known as the cut off. During stimulation, the latency of the withdrawal increased to ≈ 70% of the maximal possible inhibition. Following stimulation, the inhibition persisted for > 1 h. Stimulation at 2 or 6 Hz elicited similar effects but stimulation at 8 Hz evoked inhibition during the stimulation only. Stimulation applied to sites away from defined meridian points inhibited tail withdrawal during the stimulation; no post-stimulation effect was produced. In acutely transected animals (≤ 48 h), stimulation of meridian points elicited a small, brief increase in latency but during stimulation only. At 7 and 14 days after spinal transection, this response during stimulation was greater in magnitude and a brief post-stimulation increase was also observed. The return of the of this latter effect was coincident with the return of bladder function. These data suggest that high intensity, low frequency electrical stimulation of hindlimb meridian points in the lightly anaesthetized rat produces both brief and persistent inhibitory effects on the nociceptive tail withdrawal reflex. These effects appear to be elicited by different mechanisms. The persistent effect may represent a plastic change in central inhibitory mechanisms. Data from spinal animals indicate a major participation of supraspinal structures but that spinal mechanisms are also capable of sustaining both types of effect.     

Parametric Studies on Electroacupuncture-Like Stimulation in a Rat Model: Effects of Intensity, Frequency, and Duration of Stimulation on Evoked Antinociception

We have found that electroacupuncture-like stimulation of defined sites in the hindlimb of the rat inhibits a nociceptive withdrawal reflex. The lightly anaesthetized rat was used and tail withdrawal from a noxious radiant heat stimulus was the nociceptive reflex. Standard stimulation of hindlimb meridian points femur-futu (ST-32), fengshi (GB-31), and zusanli (ST-36) consisted of a 2-ms square voltage pulse at 4 Hz for a duration of 20 min, applied at 20 times the threshold to evoke muscle twitch. This produced two types of inhibition of the reflex; one was an increase in the latency of up to 80% during the stimulation, termed the brief antinociception, and the other was a post stimulation increase of up to 60% lasting greater than 1 h, termed the persistent antinociception. When the stimulus intensity was reduced to 10 times threshold, the latency during stimulation increased up to 50%, but the persistent response did not occur. Stimulation at threshold produced neither effect. When the train duration was altered, 10 min of stimulation produced only the brief effect, whereas 40 min of stimulation produced both effects, although the persistent effect lasted only 20 min. Stimulation at 6 Hz produced responses similar to those at 4 Hz, whereas stimulation at 2 Hz produced smaller effects. At 8 Hz, only the brief antinociception was elicited. With a pulse duration of 0.2 ms, the brief response was observed but the persistent response was markedly attenuated, whereas 5 ms produced responses similar to those with 2 ms. These data suggest that high-intensity, low-frequency electrical stimulation of meridian points in the rat hindlimb produces both brief and persistent antinociceptive effects on the tail withdrawal reflex, and both effects are dependent upon the parameters of stimulation. The persistence of the latter effect beyond the period of stimulation suggests events occurring after direct synaptic activity, possibly mediated via plastic changes at spinal and/or supraspinal levels.     

Influence of L-DOPA on transmission in long ascending propriospinal pathways in the cat

In high spinal cats the influence of an intravenous injection ofl-3,4,-dihydroxyphenylalanine (DOPA) has been investigated on the transmission of long ascending propriospinal pathways to certain groups of forelimb motoneurones. The early discharge evoked in pectoralis major and deep radial motoneurones on electrical stimulation of hindlimb afferents, which may be obtained in some high spinal preparations, is facilitated after DOPA. A late discharge (30–80 msec) appears after DOPA in the same forelimb motoneurones and may often last up to 600 msec or more. Facilitation by hindlimb nerves of forelimb mono- and polysynaptic reflexes is similarly prolonged. Ipsilateral hindlimb nerves are more effective than contralateral. Late discharges have also been evoked in forelimb motoneurones on stimulation of forelimb afferents after DOPA and it is concluded that a somewhat similar organization of late reflexes exists in brachial segments as previously reported by Jankowskaet al. in the lumbar cord.The influence of DOPA on long ascending propriospinal and forelimb reflexes is ascribed to excitation of the terminals of noradrenergic reticulospinal fibres. The reflex changes are considered to reflect activity in neuronal systems involved in the control of stepping in the cat.A further system modifying long ascending propriospinal transmission could be excited by stimulation of the ventral quadrant of the spinal cord at C₁. The effects on propriospinal transmission could outlast the stimulus by several tens of minutes.     

Reflex mechanisms of interlimb interrelationships displayed in lumbar flexor centers of the cat spinal cord]

Interaction of segmental, propriospinal and spino-bulbo-spinal components of the lumbar flexor reflexes evoked by activation of the hind-and forelimb afferents with paired stimuli was studied in anesthetized cats. Coincidence in time of a reflex discharge evoked by stimulation of the forelimb afferent nerves with monosynaptic hindlimb flexor reflex causes considerable facilitation of the latter. The monosynaptic reflex increases for 40-50 ms. tthe polysynaptic flexor reflexes of segmental, propriospinal and spino-bulbo-spinal origin act upon each other in both a facilitatory and an inhibitory manner. Facilitation takes place only during the period of coincidence of the responses, inhibition when the responses are separated in time. Three types of inhibition with duration of 7-15, 40-150, 300-500 ms were observed. Possible neuronal mechanisms of interaction of the above-mentioned responses and their role in the inter limb interrelations are discussed     

Functional organization of long ascending propriospinal pathways linking lumbo-sacral and cervical segments in the cat

In high spinal cats propriospinal pathways ascending from lumbo-sacral levels of the spinal cord can mediate strong excitatory and inhibitory changes in reflexes to different groups of motoneurones supplying muscles of the forelimb. Discharges evoked by electrical stimulation of hindlimb nerves could be evoked in 41% of experiments in the motoneurones of pectoralis major and minor. The latency of the discharge (8–18 msec) could be shortened by increasing the repetition frequency of the stimulus, the greatest reduction occurring in the range 1–4 Hz. Contralateral hindlimb nerves were less effective and the discharge generally occurred at a latency 1–2 msec longer than for ipsilateral nerves.Monosynaptic reflexes to pectoralis major and deep radial motoneurones supplying the physiological flexor muscles were strongly facilitated by hindlimb nerve stimulation, ipsilateral nerves being more effective than contralateral. Monosynaptic reflexes to latissimus dorsi showed a reciprocal pattern of conditioning, being depressed by ipsilateral and facilitated by contralateral hindlimb extensor nerves, the flexor nerves giving the reverse pattern. Monosynaptic reflexes to median and ulnar nerves supplying physiological extensor muscles were not significantly affected by hindlimb nerve conditioning.Polysynaptic reflexes to pectoralis major and deep radial motoneurones received initial strong facilitation followed by prolonged depression, ipsilateral hindlimb nerves being more effective than contralateral. In latissimus dorsi a reciprocal pattern similar to that for monosynaptic reflex testing was found. Polysynaptic reflexes to median and ulnar motoneurones received only prolonged depression.The hindlimb afferent nerves responsible for the discharge in forelimb motoneurones and for the facilitation and depression of forelimb reflexes include groups II and II muscle afferents and group II skin afferents, especially from quadriceps and sartorius muscles, and sural and superficial peroneal nerves, respectively.The ascending long propriospinal pathways are influenced bilaterally from hindlimb nerves and are located in the lower thoracic segments in the ventrolateral funiculus. The pathways mediate effects on ipsilateral and contralateral forelimb reflex systems, the ipsilateral projections being dominant. Part of the long ascending projection terminates monosynaptically on the motoneurones of pectoralis major. It is likely that group II afferents from ipsilateral quadriceps muscle activate the ascending tract monosynaptically and those from contralateral quadriceps disynaptically.The hypothesis is suggested that long propriospinal paths primarily represent intrinsic links between hindlimb and forelimb ‘motor centres’. The pattern of long ascending influences to groups of forelimb motoneurones corresponds closely to the sequences of hindlimb and forelimb stepping observed in normal cats. A functional role in stepping is therefore proposed for long ascending propriospinal pathways.     

Functional organization of the spinal reflex pathways from forelimb afferents to hindlimb motoneurons in the cat. II. Conditions of the interneuronal connections

The interneuronal conditionsof the descending pathways from forelimb afferents to hindlimb motoneurones were investigated by testing spatial interactions in these pathways and between these pathways and segmental lumbar reflex pathways. In high spinal unanaesthetized cats hindlimb motoneuroneswere intracellularly recorded and spatial interactions were tested between effects evoked by stimulation of pairs of ipsi- and contralateral forelimb nerves or pairs of a forelimb and an ipsilateral hindlimb nerve. The excitatory and late inhibitory pathways from forelimb afferents projecting to most of the hindlimb motoneurone pools, showed an interactive pattern which was distinctly different to the fast inhibitory pathway projecting specifically for ipsilateral forelimb afferents to flexor digitorum and hallucis longus (FDHL) motoneurones. Stimulation of homonymous or heteronymous pairs of two forelimb nerves of both sides evoked generally a distinct spatial facilitation of the excitatory and late inhibitory effects, while the specific early IPSPs to FDHL motoneurones were not facilitated. Paired stimulation of two forelimb nerves of one side only produced spatial facilitation of EPSPs or late IPSPs if low strength stimuli were used, using higher strength which induced larger effects, generally caused occlusion instead. In case of large IPSPs this may be due to the vicinity to the equilibrium potential. Except for an inhibition of cutaneous reflex pathways, the spatial interaction of the excitatory and late inhibitory pathways onto segmental lumbar reflex pathways was weak and variable. The fast inhibitory pathway to FDHL motoneurone showed a partial spatial facilitatory interaction with lumbar reflex pathways from cutaneous and group II muscle afferents. The second IPSP wave evoked by this pathway was inhibited by antidromic stimulation of the ventral root L7S1 and of the α-efferents of the antagonistic peroneal nerve. From the results conclusions are drawn on the interneuronal organization of the descending pathways from forelimb afferents to hindlimb motoneurones.     

Functional organization of the spinal reflex pathways from forelimb afferents to hindlimb motoneurones in the cat. II. Conditions of the interneuronal connections

The interneuronal conditions of the descending pathways from forelimb afferents to hindlimb motoneurones were investigated by testing spatial interactions in these pathways and between these pathways and segmental lumbar reflex pathways. In high spinal unanaesthetized cats hindlimb motoneurones were intracellularly recorded and spatial interactions were tested between effects evoked by stimulation of pairs of ipsi- and contralateral forelimb nerves or pairs of a forelimb and an ipsilateral hindlimb nerve. The excitatory and late inhibitory pathways from forelimb afferents projecting to most of the hindlimb motoneurone pools, showed an interactive pattern which was distinctly different to the fast inhibitory pathway projecting specifically from ipsilateral forelimb afferents to flexor digitorum and hallucis longus (FDHL) motoneurones. Stimulation of homonymous or heteronymous pairs of two forelimb nerves of both sides evoked generally a distinct spatial facilitation of the excitatory and late inhibitory effects, while the specific early IPSPs to FDHL motoneurones were not facilitated. Paired stimulation of two forelimb nerves of one side only produced spatial facilitation of EPSPs or late IPSPs if low strength stimuli were used, using higher strength which induced larger effects, generally caused occlusion instead. In case of large IPSPs this may be due to the vicinity to the equilibrium potential. Except for an inhibition of cutaneous reflex pathways, the spatial interaction of the excitatory and late inhibitory pathways onto segmental lumbar reflex pathways was weak and variable. The fast inhibitory pathway to FDHL motoneurones showed a partial spatial facilitatory interaction with lumbar reflex pathways from cutaneous and group II muscle afferents. The second IPSP wave evoked by this pathway was inhibited by antidromic stimulation of the ventral root L7S1 and of the alpha-efferents of the antagonistic peroneal nerve. From the results conclusions are drawn on the interneuronal organization of the descending pathways from forelimb afferents to hindlimb motoneurones.     

Organization of adult motor cortex representation patterns following neonatal forelimb nerve injury in rats

Somatotopic representation patterns in the motor cortex (MI) of rats that had a unilateral forelimb amputation on the first postnatal day were examined after 2-4 months of survival. Intracortical electrical stimulation and recording techniques were used to map the somatic representation in MI and in the somatic sensory cortex (SI). In normal rats, vibrissa, forelimb, and hindlimb areas comprise the bulk of the MI representation. Stimulation within the forelimb area elicits elbow, wrist, or digit movements at the lowest current intensities. The proximal limb representation appears to be contained within the distal forelimb area, since shoulder movements are nearly always evoked by stimulating at higher current intensities at some distal forelimb sites. In agreement with previous studies, the distal forelimb representation overlapped the adjacent part of the granular SI cortex. Following removal of the forelimb at birth, 3 novel features of MI organization were observed. First, the areas from which stimulation evoked movements of the vibrissa or the shoulder musculature were larger than normal. Stimulation thresholds were lower than those required for comparable movements in normal rats throughout these areas, suggesting that nerve section had not simply unmasked a high-threshold representation. Second, vibrissa movements were more commonly paired with movements of the proximal forelimb muscles at the same site. Third, stimulation in the adjacent granular SI cortex failed to evoke shoulder or trunk movements, although receptive-field mapping in this region showed that cells were responsive to cutaneous stimulation of the trunk and shoulder region. These results indicate that several organizational features develop differently in MI following perinatal nerve injury: certain remaining muscle groups have enlarged cortical representations, there is a strengthening of some normally weak connections from MI to the proximal musculature, and muscles are grouped in unusual combinations. These data demonstrate that the formation of MI representation patterns is strongly influenced by nerve injury during the perinatal period.     

Suppression of the hindlimb flexor reflex by stimulation of the medial hypothalamus and thalamus in the rat

Pentobarbital-anesthetized rats received electrical hindpaw stimulation every 10 s to elicit a maximal hindlimb withdrawal reflex. The integrated EMG response in the ipsilateral tibialis anterior was sampled by a computer which also controlled the timing of electrical stimuli applied to the brain. A suppression of the evoked flexor activity was obtained with currents below 0.05 mA for stimuli applied in the medial hypothalamic region. A second effective site was located in the paraventricular area of the thalamus. The suppression had an onset latency of 30 ms, increased over a period of 500 ms and was followed by a postinhibitory facilitation (rebound). When the noxious electrical shocks were given over prolonged periods (140 s) the suppression of the flexor reflex was seen to outlast the central stimulation by more than 100 s. Intravenous injection of naloxone or methysergide failed to reverse the effects of the brain stimuli. It is suggested that the hypothalamic induced inhibition of withdrawal reflexes is functionally meaningful in view of the incompatibility between these reflexes and the locomotor behavior which is part of the behavioral responses (i.e. fight or flight) controlled by this area.     

Modular organization of human leg withdrawal reflexes elicited by electrical stimulation of the foot sole.

Human withdrawal reflex receptive fields were determined for leg muscles by randomized, electrical stimulation at 16 different positions on the foot sole. Tibialis anterior, gastrocnemius medialis, peroneus longus, soleus, rectus femoris, and biceps femoris reflexes, and ankle joint angle changes were recorded from 14 subjects in sitting position. Tibialis anterior reflexes were evoked at the medial, distal foot and correlated well with ankle dorsal flexion. Gastrocnemius medialis reflexes were evoked on the heel and correlated with plantar flexion. Stimulation on the distal, medial sole resulted in inversion (correlated best with tibialis anterior activity), whereas stimulation of the distal, lateral sole evoked eversion. Biceps femoris reflexes were evoked on the entire sole followed by a small reflex in rectus femoris. A detailed withdrawal reflex organization, in which each lower leg muscle has its own receptive field, may explain the ankle joint responses. The thigh activity consisted primarily of flexor activation.     

Reflex effects evoked by stimulation of hypoglossal afferent fibers

In pentobarbitone-anesthetized cats, electrical stimulation of the central ends of the main trunks of transected hypoglossal nerves evoked vascular (pressor or depressor) reactions, mydriasis, slow and deep breathing, and reflex activation of laryngeal and facial muscles. Stimulation of the central end of the transected ramus descendens hypoglossi also provoked reflex contraction of cricothyroideus. These reflexes may be elicited also after intracranial section of hypoglossal nerve roots, but not after intracranial section of ipsilateral vagal roots. The above reflexes were abolished by acute section of the ipsilateral hypoglossonodosal branch, but they may be reproduced by electrical stimulation of the central end of this anastomotic branch between hypoglossal nerve and nodose ganglion. Stimulation of the central end of one transected hypoglossus evoked reflex efferent discharges in contralateral hypoglossus and contraction of contralateral tongue muscles. Stimulation of the central end of one transected hypoglossal end-branch inhibited efferent discharges in another end-branch. The crossed hypoglossohypoglossal reflex and the ipsilateral reflex inhibition were abolished by section of the hypoglossonodosal branch or vagal roots at the stimulated side. We conclude that reflexes evoked by stimulation of peripheral hypoglossal nerve in cats are mediated by afferent fibers directed to the nodose ganglion and entering the brain stem via vagal roots.     

Movement representation in the dorsal and ventral premotor areas of owl monkeys: A microstimulation study

We used intracortical microstimulation to investigate the lateral premotor cortex and neighboring areas in 14 hemispheres of owl monkeys, focusing on the somatotopic distribution of evoked movements, thresholds for forelimb movements, and the relative representation of proximal and distal forelimb movements. We elicited movements from the dorsal and ventral premotor areas (PMD, PMV), the caudal and rostral divisions of primary motor cortex (Mlc, Mlr), the frontal eye field (FEF), the dorsal oculomotor area (OMD; area 8b), the supplementary motor area (SMA), and somatosensory cortex (areas 3a and 3b). Area PMD was composed of architectonically distinguishable caudal and rostral subdivisions (PMDc, PMDr). Stimulation of PMD elicited movements of the hindlimb, forelimb, neck and upper trunk, face, and eyes. Hindlimb and forelimb movements were represented in the caudalmost part of PMDc. Face, neck, and eye movements were represented in the lateral and rostral parts of PMDc and in PMDr. Stimulation of PMV elicited forelimb and orofacial movements, but not hindlimb movements. Both proximal and distal forelimb movements were elicited from PMDc and PMV, although PMD stimulation elicited mainly shoulder and elbow movements, while PMV stimulation evoked primarily wrist and digit movements. Distal movements were evoked more frequently from PMV than from Mlr or Mlc. Across cases, the median forelimb thresholds for PMDc and PMV were 60 and 36 μA, respectively, values that differ significantly from each other and from the value of 11 μA obtained for Mlr. Our observations indicate that premotor cortex is much more responsive to electrical stimulation than commonly thought, and contains a large territory from which eye movements can be elicited. These results suggest that in humans, much of the electrically excitable cortex located on the precentral gyrus, including cortex sometimes considered part of the frontal eye field, is probably homologous to the premotor cortex of nonhuman primates. © 1996 Wiley-Liss, Inc.     

Modulation of the jaw-opening reflex by peripheral electrical stimulation

Modulation of the jaw-opening reflex (JOR) by peripheral electrical stimulation was studied in the rat. The JOR was evoked by electrical stimuli delivered to the tongue, infraorbital nerve, or tooth pulp chamber, and single-pulse conditioning stimuli were delivered to the forelimb, hind limb, or tail. Threshold current for eliciting the JOR was modulated in a biphasic manner with facilitation when the delay between conditioning and test stimuli was short (peaking at 10 to 15 ms) and inhibition at longer intervals (peaking at 40 to 60 ms). Modulation was similar for all peripheral conditioning sites and was not affected by Fentanyl, naloxone, or picrotoxin. Thus, the modulation of the JOR by single-pulse peripheral electrical stimulation is a widespread, nonsegmental phenomenon, and is probably not associated with the endogenous opiate system. Data collected during the course of this study call into question the usefulness of the JOR elicited by electrical stimulation in the rat incisor tooth pulp chamber as a pain model.     

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.     

Influence of spinalization on spinal withdrawal reflex responses varies depending on the submodality of the test stimulus and the experimental pathophysiological condition in the rat

The influence of midthoracic spinalization on thermally and mechanically induced spinal withdrawal reflex responses was studied in the rat. There were three experimental groups of rats: healthy controls, rats with a spinal nerve ligation-induced unilateral neuropathy, and rats with a carrageenan-induced inflammation of one hindpaw. Tail flick response was induced by radiant heat. Hindlimb withdrawal was induced by radiant heat, ice water, and innocuous or noxious mechanical stimulation of the paw. Prior to spinalization, spinal nerve ligated and carrageenan-treated animals had a marked unilateral allodynia and hyperalgesia. Spinalization tended to induce a facilitation of noxious heat-evoked reflexes. This spinalization-induced facilitation was stronger on tail than hindlimb withdrawal. Spinalization-induced skin temperature change did not explain the facilitation of noxious heat-evoked reflexes. In contrast, spinal withdrawal responses induced by noxious cold or mechanical stimulation were significantly suppressed following spinalization. The spinalization-induced facilitatory effects as well as inhibitory ones on spinal reflexes were enhanced in inflamed/neuropathic animals. The results indicate that the tonic descending control of spinal nocifensive responses varies depending on the submodality of the test stimulus, the segmental level of the reflex (tail vs. hindlimb), and on the pathophysiological condition.     

Extracellular space volume changes in the rat spinal cord produced by nerve stimulation and peripheral injury

Double-barrelled potassium and tetramethylammonium-sensitive microelectrodes were used in diffusion studies with tetramethylammonium ions, which remain essentially extracellular during the measurements. Activity-related changes in the extracellular space (ECS) volume fraction (), ECS tortuosity (γ) and the dynamics of the ECS volume changes were examined in the spinal dorsal horns of rats. The and γ in L₄ and L₅ segments of unstimulated rats werea = 0.24 ± 0.01 (i.e. ECS occupied24 ± 1% of the total spinal cord volume) andγ = 1.54 ± 0.04 (mean ± S.D. of mean, n = 21). The values were not significantly different throughout the dorsal horn. Repetitive electrical stimulation of peripheral nerves at 3-100 Hz increased extracellular potassium concentration ([K⁺]_e) and ECS volume in Rexed laminae III-V by15.8 ± 2.7% (n = 5). After the end of stimulation, when the [K⁺]_e decreased below the original baseline (K⁺ undershoot), the ECS volume decreased by 20–45%. The magnitude and duration of ECS volume decrease were positively related to the stimulation frequency and duration. The ECS volume decrease was maximal at 2–10 min after the stimulation had been discontinued, and it returned to the prestimulation values in 15–40 min. The ECS volume decreased by 20–50% after injury of the ipsilateral hind paw evoked either by subcutaneous injection of turpentine (n = 5), or by thermal injury (n = 6). The maximal changes were found in Rexed laminae III–V, 5–10 min after injection of turpentine and 10–25 min after thermal injury, and persisted for more than 120 min and 30 min, respectively. The tortuosity of the ECS was not significantly altered by stimulation or injury. Our measurements indicate that the dynamic changes in the spinal cord ECS volume accompany transmembrane ionic shifts during and long after neural activity which had been evoked by peripheral stimulation or injury.     

Patterning of sympathetic nerve activity in response to vestibular stimulation

Growing evidence suggests a role for the vestibular system in regulation of autonomic outflow during postural adjustments. In the present paper we review evidence for the patterning of sympathetic nerve activity elicited by vestibular stimulation. In response to electrical activation of vestibular afferents, firing of sympathetic nerves located throughout the body is altered. However, activity of the renal nerve is most sensitive to vestibular inputs. In contrast, high-intensity simultaneous activation of cutaneous and muscle inputs elicits equivalent changes in firing of the renal, superior mesenteric and lumbar colonic nerves. Responses of muscle vasoconstrictor (MVC) efferents to vestibular stimulation are either inhibitory (Type I) or are comprised of a combination of excitation and inhibition (Type II). Interestingly, single MVC units located in the hindlimb exhibited predominantly Type I responses while those located in the forelimb and face exhibited Type II responses. Furthermore, brachial and femoral arterial blood flows were dissociated in response to vestibular stimulation, such that brachial vascular resistance increased while femoral resistance decreased. These studies demonstrate that vestibulosympathetic reflexes are patterned according to both the anatomical location and innervation target of a particular sympathetic nerve, and can lead to distinct changes in local blood flow.     

Multi-joint movement of the cat hindlimb evoked by microstimulation of the lumbosacral spinal cord

Microstimulation of the lumbosacral spinal cord may be an effective tool for the restoration of locomotion after spinal cord injury. To examine this possibility, complex coordinated multi-joint hindlimb movements were evoked by electrical stimulation with sine waveform modulation using a single microelectrode positioned in the L5–S1 spinal cord. Four types of hindlimb movement (flexion, extension, abduction, and adduction) were identified, and their stimulation locations were mapped onto cross-sectional drawings of L5–S1 spinal cord following histological examination of electrode tracks in the cord. Hindlimb flexion was evoked without abduction/adduction at many locations in the dorsal part of the L5–S1 spinal cord, whereas extension was evoked with abduction/adduction in the ventral part of the cord. Bilateral reciprocal lifting of the hindlimb was evoked by implanting two microelectrodes (one on each side) in the spinal cord. This study indicates that functional hindlimb movements can be elicited by activating a small number of sites in lumbosacral spinal cord.     

Functional organization of the spinal reflex pathways from forelimb afferents to hindlimb motoneurones in the cat

The effects of electrically stimulated forelimb afferents on hindlimb motoneurones of high spinal cats were investigated by means of intracellular recordings. The results revealed four essential findings: (1) EPSPs with a minimum latency of 5.6 msec, measured from the incoming volley recorded at C6; (2) IPSPs with a minimum latency of 8 msec, often superimposed on the EPSPs; (3) long lasting, late hyperpolarizations with a latency of 25–60 msec; and (4) early IPSPs with a minimum latency of 3.1 msec evoked exclusively in FDL motoneurones. With the exception of sartorius motoneurones, which received almost pure inhibition, combined excitatory-inhibitory effects were observed in all species of hindlimb motoneurones, although the effects in ankle extensors (GS, P1) were generally larger than those in ankle flexors (DP, SPM). The relation between excitation and inhibition was variable, so that in extreme cases almost pure EPSPs or IPSPs could occur. Except for their time course, the conditions for mediating EPSPs and IPSPs were similar: they were evoked from medium to high threshold afferents of both sides and were easily diminished by increasing the stimulation frequency. It is discussed whether, although the excitatory and inhibitory pathways are activated together, the final action on a motoneurone is dependent on the phase or position of the hindlimb.By comparison, the early IPSP evoked specifically in FDL motoneurones had fundamentally different characteristics: it was mainly evoked from low threshold afferents of more distal cutaneous or mixed nerves from the ipsilateral side only and it followed stimulus frequencies up to about 100 Hz. It is proposed that this inhibition prevents plantar flexion of the toes during the first extension phase of the hindlimb.     

The somatotopic organization of the supplementary motor area: intracortical microstimulation mapping

The somatotopic organization of the supplementary motor area (SMA) is commonly held to consist of a rostrocaudal sequence of orofacial, forelimb, and hindlimb representations. Recently, however, this somatotopy has been questioned. Studies of regional cerebral blood flow in humans and the movements evoked by intracortical electrical stimulation in cynomolgus monkeys have been unable to reveal evidence of distinct orofacial, forelimb, and hindlimb representations rostrocaudally situated along the medial cortex of the hemisphere. Partly on the basis of those results, it has been suggested that the SMA functions as a nontopographically organized "higher-order" motor center. The present study reexamines SMA organization by observing stimulation-evoked movements. The medial frontal cortex of 2 rhesus monkeys was mapped using a modified intracortical microstimulation technique. We observed a forelimb representation mainly on the medial surface of the hemisphere in both animals. Rostral or rostrolateral to the forelimb representation, depending on the individual, we evoked orofacial movements (including eye movements). Hindlimb movements were evoked from tissue overlapping, but largely caudal to, the forelimb representation. Thus, we conclude that there is a clear rostrocaudal progression of orofacial, forelimb, and hindlimb movement representations in the SMA.