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.     

Modulation of jaw reflexes induced by noxious stimulation to the muscle in anesthetized rats

Previous studies have shown that jaw reflexes and activity patterns of the jaw muscles were modulated in the presence of jaw muscle pain. However, there is no study comparing the modulatory effects on the jaw reflexes induced by noxious stimulation to the jaw muscle. To clarify this, effects of the application of mustard oil (MO), an inflammatory irritant, into the temporalis (jaw-closing) muscle on (1) jaw-opening reflex evoked by tooth pulp stimulation (TP-evoked JOR) as a nociceptive reflex, (2) jaw-opening reflex evoked by inferior alveolar nerve stimulation as a non-nociceptive reflex and (3) jaw-closing reflex evoked by trigeminal mesencephalic nucleus stimulation as a proprioceptive reflex were investigated in anesthetized rats. The MO application induced suppression of all reflexes, and the effect on the TP-evoked JOR was more prominent than on the other reflexes. To elucidate the involvement of endogenous opioid system for the suppressive effect, a systemic administration of naloxone following the MO application was conducted. The MO-induced suppressive effect on the TP-evoked JOR was reversed by the naloxone administration. The results suggest that noxious stimulation to the jaw muscle modulate jaw reflexes particularly for the nociceptive jaw-opening reflex, and the modulatory effect includes both facilitatory and inhibitory aspects. The results also suggest that pain modulatory systems such as the endogenous opioid system play a crucial role in the suppression of the nociceptive transmissions related to nociceptive reflexes, and in some pathological states, defense reflexes may not be evoked properly.     

Depression of the human nociceptive withdrawal reflex by segmental and heterosegmental intramuscular electrical stimulation.

OBJECTIVE: To investigate the effects of intramuscular electrical conditioning in the modulation of nociceptive withdrawal reflex (NWR) and further to determine what muscle afferents are involved in the modulation of the nociceptive withdrawal reflex and the sites along the reflex pathway where the NWR modulation occurs in healthy humans. METHODS: The NWR elicited by a cutaneous test stimulus to the dorsal foot was modulated by a short (21 ms) intramuscular conditioning electrical stimulus at two times the pain threshold. At varying conditioning-test stimulus intervals, segmental conditioning stimulus was applied in the tibialis anterior muscle ipsilateral and contralateral to the test stimulus, and heterosegmental conditioning stimulus was applied in the contralateral trapezius muscle to modulate the NWR. Non-painful and painful intramuscular conditioning stimuli were also used to modulate the NWR and the soleus H-reflex. RESULTS: The NWR was depressed by preceding intramuscular conditioning stimuli, with a degree that depended on the conditioning-test stimulus intervals and on the conditioning site. Segmental conditioning depressed the NWR more quickly and gave a longer duration (15-1500 ms), and larger magnitude than heterosegmental conditioning, which depressed the NWR in a short temporal window (80-100 ms). No difference was seen in the magnitude of the NWR depression between the painful and non-painful intramuscular stimuli, and the soleus H-reflex was not affected. CONCLUSIONS: Our results suggest that segmental and heterosegmental conditionings of NWR are mediated by myelinated muscle afferents engaging central inhibitory mechanisms rather than direct changes in the excitability of motor neurons. SIGNIFICANCE: The therapeutic effects of electrotherapy could involve these mechanisms in the treatment of muscle pain syndromes.     

Conditioning of the masseter inhibitory reflex by homotopically applied painful heat in humans

During contraction of the jaw-closing muscles, afferent input from the intraoral and perioral region can elicit two bilateral suppression periods (SP1 and SP2, respectively) in the masseter electromyogram (EMG). Non-painful electrical stimulation 2 cm from the left labial commissure was used in the present study to evoke these trigeminal inhibitory reflexes. The subjects maintained a level of 50% of their maximum masseter EMG. The degree of suppression was quantified as the percentage suppression of the mean EMG activity in a fixed post-stimulus interval (SP2, 40-90 ms). Further, brief (200 ms) painful radiant heat conditioning stimuli were delivered to the ipsilateral cheek, in order to investigate the influence of nociceptive input on the (non-nociceptive) trigeminal masseter inhibitory reflex. Nine different conditions combining radiant heat and electrical stimuli were used. Twelve stimuli were presented for each condition. The radiant heat preceded the electrical test stimuli by fixed inter-stimulus intervals (ISI), ranging from 100 ms to 500 ms. At 250-350 ms ISIs, the bilateral SP2 suppression was significantly reduced to less than 10%, in comparison to an average suppression degree of 32.5% without conditioning stimuli. The subjects perceived the heat stimulus before the electrical stimulus for a majority of the 12 pairs of stimuli at these ISIs. No differences were found in the VAS ratings for the different conditions. For the contralateral SP1, larger suppression was seen for the 300 ms ISI compared with stimulation without conditioning heat stimuli. Onset and offset for the SP1 was, however, only detected in three subjects using a criteria of 20% suppression of the pre-stimulus activity. A pre-pulse inhibitory effect onto inter-neurons in the SP2 pathways or habituation of the same inter-neurons by the heat stimuli are suggested as possible explanations for the interaction between the non-nociceptive and nociceptive input in the present study.     

Diffuse noxious inhibitory controls in humans: A neurophysiological investigation of a patient with a form of Brown-Séquard syndrome

In normal subjects, the application of heterotopic painful stimuli induces simultaneous and parallel decrease in the sensation of pain and of the spinal nociceptive flexion (R_III) reflex evoked by electrical stimulation of the sural nerve. This inhibition of the R_III reflex is absent in tetraplegic patients with clinically complete spinal cord transections and can be triggered only from the analgesic hand in patients with Wallenberg's syndrome. These findings suggest that the inhibitory phenomena observed in normal subjects are likely to be examples of diffuse noxious inhibitory controls (DNICs), being sustained by a loop involving supraspinal structures, the ascending part of which is localized in the spinoreticular tract. We now report an exceptional case of a patient with Brown-Séquard syndrome due to a 4-year-old spinal cord lesion (left side, T-6 level) produced by a knife-wound in the back. Nociceptive flexion (R_III) reflexes elicited by stimulation of cutaneous afferents in the ulnar and sural nerves were studied in the upper and lower limbs by recording from the biceps brachialis and biceps femoris muscles, respectively. For each limb, the R_III reflex threshold was determined. The reflex was then elicited regularly by stimuli of 1.2 times threshold before, during, and after periods of nociceptive electrical conditioning stimulation (15 mA; 4Hz; 1 min) applied successively to the other three limbs. Inhibitions of around 90% followed by after effects (2–3 min) were observed in all situations except that (1) no inhibition could be obtained when the conditioning stimuli were applied to the lower right limb (contralateral to the spinal lesion) and (2) the R_III reflex in the lower left limb was completely insensitive to any of the conditioning stimuli. These results suggest that in humans (1) the ascending part of the loop subserving DNICs is completely crossed at the spinal level and (2) the descending part is confined to the white matter ipsilateral to the limb being tested.     

Sensorimotor integration in patients with parkinsonian type multisystem atrophy

Sensorimotor integration is an essential feature of the central nervous system that contributes to the accurate performance of motor tasks. Some patients with multiple system atrophy with parkinsonian features (MSAp) exhibit clinical signs compatible with an abnormal central nervous system excitability to somatosen– sory inputs, such as action myoclonus or enhanced cutaneo–muscular reflexes. To investigate further the site where such dysfunction in sensorimotor integration takes place, we examined the inhibitory effects of a cutaneous afferent volley at two different levels of the motor system in 10 MSAp patients and in 10 agematched healthy volunteers. Electrical digital nerve stimuli were given as the conditioning stimulus for the motor evoked potentials (MEP) elicited by transcranial magnetic stimulation in hand muscles, and for the blink reflex responses obtained in the orbicularis oculi muscles by supraorbital nerve stimulation. Intervals for the conditioning were 20 to 50ms for the MEP and 90 to 110ms for the blink reflex. The MEP was significantly inhibited in test trials in healthy volunteers, reaching a mean of 32% of the baseline values at the ISI of 35 ms. Significant inhibition occurred also in the blink reflex, in which the R2 response was a mean of 12% of baseline values at the ISI of 100 ms. The inhibitory effects were abnormally reduced in 8 patients on the MEP, and in 7 patients on the blink reflex. There were significant group differences between patients and control subjects in the size of the conditioned MEP and blink reflex. These results suggest that sensorimotor integration is abnormal in patients with MSAp in at least two central nervous system sites: the sensorimotor cortex, and the brainstem reticular formation.     

Differential effects of plantar cutaneous afferent excitation on soleus stretch and H‐reflex

Previous studies have demonstrated that plantar cutaneous afferents can adjust motoneuron excitability, which may contribute significantly to the control of human posture and locomotion. However, the role of plantar cutaneous afferents in modulating the excitability of stretch and H‐reflex with respect to the location of their excitation remains unclear. In the present study, it was hypothesized that electrical stimulation delivered to the sole of the foot might be followed by modulation of spinal excitability that depends on: (1) the stimulation location and (2) the reflex studied. In these experiments, conditioned and unconditioned stretch and H‐reflexes were evoked in 16 healthy subjects in a seated position. Both reflexes were conditioned by non‐noxious electrical plantar cutaneous afferent stimulation at two different sites, the heel and metatarsal regions, at four different conditioning–test (CT) intervals. The conditioning stimulation delivered to the heel caused a significant facilitation of the soleus stretch reflex for all CT intervals, whereas the soleus H‐reflex had significant facilitation only at CT interval of 50 ms and significant inhibition at longer CT intervals. Stimulation delivered to the metatarsal region, however, resulted mainly in reduced stretch and H‐reflex sizes. This study extends the reported findings on the contribution of plantar cutaneous afferents within spinal interneuron reflex circuits as a function of their location and the reflex studied. Muscle Nerve, 2008     

Inhibitory effects from various types of dorsal column and raphe magnus stimulations on nociceptive withdrawal flexion reflexes

Most of the clinical and research reports agree about the analgesic effects of dorsal column (DC) stimulation, but there is no unanimity about the neural mechanisms involved in this stimulation. The aim of the present study was to compare the effects of segmental and rostral activation of the DCs and to investigate whether these effects are mediated through a brainstem spinal loop. Decerebrate-decerebellate cats were subjected to selective DC lesions at C(1) and C(3) spinal cervical levels and their reflex reactions to natural or electrical nociceptive stimuli were monitored either as withdrawal flexion reflexes or as motorneuronal discharges. Conditioning stimulation was performed as train of shocks (100 Hz, for 1 to 10 min or 300 Hz for 30 ms) applied on the DCs either rostral (DCr) or caudal (DCc) to the spinal lesions or on the raphe magnus (RM). Conditioning trains for 5-10 min applied on DCr inhibited the withdrawal flexion reflexes recorded as toe flexion (90% of the control). Comparisons of the effects of DCr, DCc or RM of conditioning stimuli were made on the discharges of 110 motorneurons recorded in isolated ventral root fibers. Conditioning stimulation applied to DCc produced short lived inhibition (in about 60%) or facilitation (in about 30% of the neurons) while DCr or RM conditioning produced inhibition in 90% of neurons which outlasted the duration of the conditioning trains. It was also shown that repetitive application of conditioning train on either DCr or RM resulted in longer duration of inhibition than that observed following DCc conditioning. We conclude that the stronger inhibition of motorneuronal discharges, evoked by nociceptive stimuli, is obtained by rostral activation of the DCs and that long term effects of DCst are mediated through a DC-brainstem-spinal loop.     

Effects of H-reflex conditioning upon the contralateral alpha motoneuron pool.

H-reflex recovery curves have been elicited by subliminal conditioning stimuli applied to the ipsilateral and contralateral posterior tibial nerves in 10 healthy female subjects. In both types of recovery curve there was clear evidence of a period of facilitation in the ipsilateral soleus motoneuron pool 75-250 msec after the conditioning stimulus. These results indicate the bilateral nature of the facilitation and show it to be most probably produced by stimulus-evoked inputs as opposed to twitch-evoked inputs. If the facilitation is produced by descending long-loop reflex influences, then complementary evidence is provided for previous electromyographic data showing the bilaterality of long-loop reflexes evoked by percutaneous electrical stimulation. It is impossible, however, at the present time, to rule out the possible involvement of cutaneous afferent discharges or other stimulus evoked inputs in the late facilitation.     

Effect of pinching-evoked pain on jaw-stretch reflexes and exteroceptive suppression periods in healthy subjects.

OBJECTIVE: To investigate the influence of conditioning cutaneous nociceptive inputs by a new "pinch" model on the jaw-stretch reflex and the exteroceptive suppression periods (ES1 and ES2) in jaw muscles. METHODS: The jaw-stretch reflex was evoked with the use of a custom-made muscle stretcher and electrical stimuli were used to evoke an early and late exteroceptive suppression period (ES1 and ES2) in the jaw-closing muscles. Electromyographic (EMG) activity was recorded bilaterally from the masseter and temporalis muscles. These brainstem reflexes were recorded in 19 healthy men (28.8+/-1.1 years) during three different conditions: one painful clip applied to the earlobe; one painful clip applied to the nostril, and four painful clips applied simultaneously to the earlobe, nostril, eyebrow, and lower lip. Pain intensity induced by the application of the clips was scored continuously by the subjects on a 100mm visual analogue scale (VAS). RESULTS: The highest VAS pain scores were evoked by placement of four clips (79+/-0.5mm). There was no significant modulation of the jaw-stretch reflex (ANOVAs: P=0.929), the ES1 (P=0.298) or ES2 (P=0.082) in any of the three painful conditions. CONCLUSIONS: Intense and tonic cutaneous pain could be elicited by this new "pinch" pain model; however, there was no significant modulation on either excitatory or inhibitory brainstem reflex responses. SIGNIFICANCE: The novel observation that high-intensity pinch stimuli applied to the craniofacial region fail to modulate two different brainstem reflexes is in contrast to other experimental pain studies documented facilitation of the jaw-stretch reflexes or inhibition of exteroceptive suppression periods. The clinical implication of the present findings is that only some craniofacial pain conditions could be expected to show perturbation of the brainstem reflex responses.     

Intense peripheral electrical stimulation differentially inhibits tail vs. limb withdrawal reflexes in the rat

In an on-going study on mechanisms by which activation of sensory afferents regulates nociception, high-intensity, low-frequency electrical stimulation was applied to previously defined meridian and non-meridian points of the hindlimb or forelimb, and the effects measured on the withdrawal reflex of the tail or limb in the lightly anesthetized rat. Withdrawal was evoked by application of noxious radiant heat to the tip of the tail or to the plantar surface of a hindpaw or forepaw. Parameters of conditioning electrical stimulation were 2 ms pulses at 4 Hz for 20 min at 20 × threshold (20–30 mA) where threshold was the minimum intensity which evoked muscle twitch. In experiments on tail withdrawal, stimulation applied to meridian points fengshi (GB-31), femur-futu (ST-32) and zusanli (ST-36) of the hindlimb or to wai-kuan (TH-5) and hoku (LI-4) of the forelimb increased the latency of the withdrawal reflex to 70–100% of the maximum possible inhibition (MPI) during the stimulation. Inhibition persisted for more than 1 h after the end of stimulation. Bilateral stimulation of hindlimb meridian points evoked a greater inhibition during the stimulation ( > 95% of the MPI); the inhibition persisted for 40 min. Stimulation of non-meridian sites in hindlimb or forelimb inhibited the withdrawal reflexes by 45–50% of the MPI during the stimulation only. Thus, the evoked inhibition has two components, a brief effect elicited by non-meridian point stimulation and a persistent post-stimulation effect produced only upon stimulation of meridian points. Stimulation produced little effect on nociceptive limb withdrawal reflexes. The results suggest that high-intensity, low-frequency electrical stimulation of meridian points produced a long-lasting, extrasegmental inhibition of the tail withdrawal but not of limb withdrawal reflexes. This differential inhibition may be due to differences in neuronal circuitry and CNS modulatory control mechanisms. The persistent inhibition appears to be dependent on the site of stimulation because it is not evoked by stimulation of sites outside of meridian points.     

Soleus H‐reflex operant conditioning changes the H‐reflex recruitment curve

Introduction: Operant conditioning can gradually change the human soleus H‐reflex. The protocol conditions the reflex near M‐wave threshold. In this study we examine its impact on the reflexes at other stimulus strengths. Methods: H‐reflex recruitment curves were obtained before and after a 24‐session exposure to an up‐conditioning (HRup) or a down‐conditioning (HRdown) protocol and were compared. Results: In both HRup and HRdown subjects, conditioning affected the entire H‐reflex recruitment curve. In 5 of 6 HRup and 3 of 6 HRdown subjects, conditioning elevated (HRup) or depressed (HRdown), respectively, the entire curve. In the other HRup subject or the other 3 HRdown subjects, the curve was shifted to the left or to the right, respectively. Conclusions: H‐reflex conditioning does not simply change the H‐reflex to a stimulus of particular strength; it also changes the H‐reflexes to stimuli of different strengths. Thus, it is likely to affect many actions in which this pathway participates. Muscle Nerve 47: [?show $1534v]–[?show $1535v], 2013     

Sensitization of enteric reflexes in the rat colon in vitro

We have investigated sensitization of reflexes in the isolated rat colon in order to develop a model that might prove useful for investigating how the sensitivity of enteric reflexes can be altered by prior stimulation. Records were taken of circular muscle tension, 7-10 mm oral and anal to radial distension exerted by a hook passed through the wall of the colon. A test stimulus of 1.5 g produced consistent contractions both oral and anal to the distension. A conditioning protocol, consisting of repeated application of 3 g for 30 s with 30 s between the stimuli for 30 min, doubled the amplitudes of reflex contractions that were evoked by the test stimuli but did not change the sensitivity of the muscle to the direct action of carbachol. The enhanced responses persisted for at least 40 min. The enhancement of reflexes was not reduced by antagonists of tachykinin NK3 receptors or of 5-HT3 receptors, but the reflex oral to stimulation was reduced by NK1 and NK3 antagonists added together. Sensitization was abolished by the cyclo-oxygenase and thromboxane synthase inhibitor, indomethacin. We conclude that sensitization can be reliably induced in vitro and that the model described in the present work can be used to investigate drugs that interfere with the sensitization process.     

Is the cutaneous silent period an opiate‐sensitive nociceptive reflex?

In humans, high-intensity electrical stimuli delivered to the fingers induce an inhibitory effect on C7-T1 motoneurons. This inhibitory reflex, called the cutaneous silent period (CSP) is considered a defense response specific for the human upper limbs. It is not clear whether the CSP-like other defense responses such as the corneal reflex and the R III reflex-is an opiate-sensitive nociceptive reflex. Because opiates suppress some, but not all, nociceptive reflexes, we studied the effect of the narcotic-analgesic drug fentanyl on the CSP and the R III reflex. The CSP was recorded from the first dorsal interosseous (FDI) muscle in seven normal subjects during voluntary contraction, before and 10 and 20 min after fentanyl injection. To assess possible fentanyl-induced changes, we also tested the effect of finger stimulation on motor evoked potentials (MEPs) elicited in the FDI muscle by transcranial magnetic stimulation before and after fentanyl injection. Fentanyl-induced changes were also studied on the R III reflex recorded from the biceps femoris muscle. Fentanyl, as expected, suppressed the R III reflex but failed to change the inhibitory effect of finger stimulation on FDI motoneurons. Finger stimulation reduced the size of MEPs in the FDI, and fentanyl injection left this inhibitory effect unchanged. The differential fentanyl-induced modulation of the CSP and R III reflex provides evidence that the CSP circuit is devoid of mu-opiate receptors and is therefore an opiate-insensitive nociceptive reflex, which may be useful in the assessment of central-acting, non-opioid drugs.     

Contralateral influences on triceps surae motoneuron excitability.

In an effort to more fully investigate spinal reflex pathways in humans, we measured the isometric force-time curve of the tibial nerve H-reflex in 12 college age subjects. We also conditioned the reflex with a contralateral H-reflex stimulus or a contralateral tendon-tap, to ascertain the effects of crossed spinal segmental inputs on alpha motoneuron excitability. The conditioning stimulus preceded the test reflex by 10, 25, 40, 55, 70, 85, 100, 115, 130 or 145 msec. The results demonstrate that a conditioning tibial nerve H-reflex produced marked facilitation onto the contralateral triceps surae motoneurons, predominantly at longer-latency intervals. Conversely, a conditioning Achilles tendon-tap produced long-latency inhibition to the triceps surae. These results demonstrate that differential motoneuron excitability changes can be produced by electrical and mechanical conditioning stimuli. Moreover, these excitability changes may be long lasting and only appear after a relatively long latency. Several neurophysiological mechanisms are proposed to contribute to these changes.     

Post-stimulus depression of reflex changes in circular muscle activity in the guinea pig small intestine.

The extent and time course of depression of successive reflex responses recorded with intracellular microelectrodes from the circular smooth muscle of the guinea pig small intestine were determined. Two stimuli were used, distension and distortion of the mucosa by compression; these were applied either at the same or at different sites. Excitatory responses oral and inhibitory responses anal to the stimuli were recorded. Post-stimulus depression of both ascending excitatory and descending inhibitory reflexes occurred, but the extent of depression was slightly less for the descending inhibition. A conditioning distension lasting 9 s depressed the excitatory response to a test distension applied 2 s later at the same site by 90%. After 30 s the depression was 50% and test responses were normal if inter-stimulus intervals were increased to 2 min. Increasing the duration of the conditioning stimulus increased the depression. Post-stimulus depression was less for compression stimuli than for distension stimuli and prior mucosal compression had almost no effect on responses to subsequent distension. The post-stimulus depression was greater if conditioning and test stimuli were at the same rather than different sites. For different sites, conditioning stimuli at 15 mm from the recording site (near) depressed responses to stimuli at 30 mm (far) to a greater extent than far stimuli depressed responses to near stimuli. If the conditioning stimulus at 15 mm was maintained until after the far test stimulus was applied, depression of the test response did not occur. It is concluded that the major sites of post-stimulus depression are at the synapses between primary sensory neurons and the first interneurons of reflex pathways, and that post-stimulus depression also occurs at other places in the pathway, presumably at synapses between interneurons or between interneurons and motor neurons.     

Flexor reflex decreases during sympathetic stimulation in chronic human spinal cord injury

A better understanding of autonomic influence on motor reflex pathways in spinal cord injury is important to the clinical management of autonomic dysreflexia and spasticity in spinal cord injured patients. The purpose of this study was to examine the modulation of flexor reflex windup during episodes of induced sympathetic activity in chronic human spinal cord injury (SCI). We simultaneously measured peripheral vascular conductance and the windup of the flexor reflex in response to conditioning stimuli of electrocutaneous stimulation to the opposite leg and bladder percussion. Flexor reflexes were quantified using torque measurements of the response to a noxious electrical stimulus applied to the skin of the medial arch of the foot. Both bladder percussion and skin conditioning stimuli produced a reduction (43–67%) in the ankle and hip flexor torques (p < 0.05) of the flexor reflex. This reduction was accompanied by a simultaneous reduction in vascular conductance, measured using venous plethysmography, with a time course that matched the flexor reflex depression. While there was an overall attenuation of the flexor reflex, windup of the flexor reflex to repeated stimuli was maintained during periods of increased sympathetic activity. This paradoxical depression of flexor reflexes and minimal effect on windup is consistent with inhibition of afferent feedback within the superficial dorsal horn. The results of this study bring attention to the possible interaction of motor and sympathetic reflexes in SCI above and below the T5 spinal level, and have implications for clinicians in spasticity management and for researchers investigating motor reflexes post SCI.     

Fear conditioned potentiation of the acoustic blink reflex in patients with cerebellar lesions

OBJECTIVE: To investigate whether the human cerebellum takes part in fear conditioned potentiation of the acoustic blink reflex. METHODS: A group of 10 cerebellar patients (eight patients with lesions involving the medial cerebellum, two patients with circumscribed lesions of the cerebellar hemispheres) was compared with a group of 16 age and sex matched healthy control subjects. The fear conditioned potentiation paradigm consisted of three phases. During the first, habituation phase subjects received 20 successive acoustic blink stimuli. In the subsequent fear conditioning phase, subjects passed through 20 paired presentations of the unconditioned fear stimulus (US; an electric shock) and the conditioned stimulus (CS; a light). Thereafter, subjects underwent the potentiation phase, which consisted of a pseudorandom order of 12 trials of the acoustic blink stimulus alone, 12 acoustic blink stimuli paired with the conditioned stimulus, and six conditioned stimuli paired with the unconditioned stimulus. The EMG of the acoustic blink reflex was recorded at the orbicularis oculi muscles. The potentiation effect was determined as the difference in normalised peak amplitude of the blink reflex evoked by pairs of CS and acoustic blink stimuli and evoked by the acoustic stimulus alone. RESULTS: In the habituation phase, short term habituation of the acoustic blink reflex was preserved in all cerebellar patients. However, in the potentiation phase, the potentiation effect of the blink reflex was significantly reduced in patients with medial cerebellar lesions compared with the controls (mean (SD) potentiation effect (%), patients: -6.4 (15.3), controls: 21.6 (35.6)), but was within normal limits in the two patients with lateral lesions. CONCLUSIONS: The present findings suggest that the human medial cerebellum is involved in associative learning of non-specific aversive reactions-that is, the fear conditioned potentiation of the acoustic blink reflex.     

The cumulative inhibitory effect of repetitively flashed stimuli on the recovery process of the human visual evoked potential to a test stimulus.

Cumulative inhibitory effects produced by visual response to flashed conditioning stimuli were measured by means of the amplitude reduction of the visual evoked potential (VEP) to a test stimulus. Four kinds of conditioning stimuli were used: a single conditioning stimulus and 3 repetitive conditioning stimuli with interstimulus intervals (ISIs) of 100, 200 and 400 msec, respectively. The VEP amplitude for the test stimulus was reduced most when the stimulus was paired with the single conditioning stimulus. It still remained small when the test stimulus was paired with the repetitive conditioning stimulus of 400 msec ISI, increased significantly when the ISI was shortened from 400 to 200 msec. Explanations of the VEP behaviors in terms of the stimulus relevance, task difficulty and the recovery rate of the cortical excitability were discussed.     

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.