Facilitation Of Reflex Research Articles

Participation of central descending nociceptive facilitatory systems in secondary hyperalgesia produced by mustard oil

The present series of experiments were designed to examine a potential role for central descending pain facilitatory systems in mediating secondary hyperalgesia produced by topical application of mustard oil and measuring the nociceptive tail-flick reflex in awake rats. Topical application of mustard oil (100%) to the lateral surface of the hind leg produced a facilitation of the tail-flick reflex that was significantly reduced in spinal transected animals. Mustard oil hyperalgesia was also inhibited in animals that had received electrolytic lesions in the rostral ventromedial medulla (RVM). Intrathecal (i.t.) administration of the non-selective cholecystokinin (CCK) receptor antagonist proglumide (10 μg) prior to mustard oil application completely blocked both the lesser and greater hyperalgesic responses observed in spinal transected and normal animals, respectively, and produced an inhibition of the tail-flick reflex in normal animals. Administration of the selective CCK B receptor antagonist L-365260 i.t. dose-dependently inhibited mustard oil hyperalgesia (ID 50 = 364 ng) at doses approximately 5-fold less than the CCK A receptor antagonist devazepide (ID 50 = 1760 ng). Similar to spinal proglumide, microinjection of the neurotensin antagonist SR48692 (3.5 μg) into the RVM blocked mustard oil hyperalgesia and inhibited the tail-flick reflex. These data suggest that secondary hyperalgesia produced by mustard oil is mediated largely by a central, centrifugal descending pain facilitatory system which involves neurotensin in the RVM and spinal CCK (via CCK B receptors). The inhibition of the tail-flick reflex produced by mustard oil following spinal or supraspinal administration of receptor antagonists suggests concurrent activation of central descending facilitatory and inhibitory systems.

M41 Facilitation of a non-nociceptive withdrawal reflex by nociceptive input in humans

M41 Facilitation of a non-nociceptive withdrawal reflex by nociceptive input in humans

Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending serotonergic systems

The centrally acting muscle relaxatn cyclobenzaprine was thought to be an α 2-adrenoceptor agoinst that reduced muscle tone by decreasing the activity of descending noradrenergic neurons. In the present study, we examined the effects of cyclobenzaprine on descending neurons by measuring the monosynaptic reflex in rats. Cyclobenzaprine reduced the monosynaptic reflex amplitude dose dependently and this effect was not inhibited by the α 2-adrenoceptor antagonists idazoxan and yohimbine. Cyclobenzaprine-induced monosynaptic reflex depression was not attenuated by noradrenergic neuronal lesions produced by 6-hydroxydopamine. However, cyclobenzaprine inhibited monosynaptic reflex facilitation induced by (±)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, a 5-HT 2 receptor agonist, in spinalized rats markedly, and 5-HT depletion by dl- p-chlorophenylalanine inhibited the depressive effect of cyclobenzaprine on the monosynaptic reflex. These results suggests that cyclobenzaprine is a 5-HT 2 receptor antagonist and that its muscle relaxant effect is due to inhibition of serotonergic, not noradrenergic, descending systems in the spinal cord.

The effect of Ketamine on stimulation of primary and secondary hyperalgesic areas induced by capsaicin -- a double-blind, placebo-controlled, human experimental study

The non-competitive NMDA-antagonist, Ketamine, was infused (i.v.) in healthy volunteers to study the effect on central excitability with the presence of cutaneous hyperalgesia. Hyperalgesia was established experimentally on the dorsum of the foot by topical application of capsaicin (1%). Different thermal and mechanical conditioning stimuli were applied to the primary and secondary hyperalgesic areas to modulate the central nociceptive excitability monitored by the nociceptive reflex. When the elicited reflex was combined with an activation of the secondary hyperalgesic area by continuous, non-painful, electrical stimulation, a facilitation of the reflex was observed. This indicates that summation of activity in non-nociceptive and nociceptive afferents can occur under mild pathological conditions. Conditioning thermal stimuli of the primary hyperalgesic area were employed to intensify the allodynia prior to testing this interaction between tactile and nociceptive activity. The same reflex facilitation was inhibited by Ketamine. Furthermore, Ketamine decreased the pain intensity associated with the stimuli eliciting the reflex. Psychophysical measures to single and repeated electrical and thermal (laser) stimuli applied within the hyperalgesic areas were also obtained. The intensity of pain sensations produced by single, painful, electrical stimuli applied to the primary hyperalgesic region was reduced after Ketamine infusion. Finally, five repeated, electrical stimuli applied to the secondary hyperalgesic area were used to assess the temporal summation threshold. Ketamine caused an increase in the summation threshold compared to the placebo treatment. In conclusion, these results demonstrate that (1) summation of activity in non-nociceptive and nociceptive afferents occurs under hyperalgesic conditions and, (2) this summation can be inhibited by NMDA-antagonists. Therefore, the study shows an apparent involvement of NMDA-receptors in some of the central mechanisms underlying secondary hyperalgesia.

Intrathecal pituitary adenylate cyclase activating polypeptide facilitates the spinal nociceptive flexor reflex in the rat.

We have examined the effects of intrathecal (i.t.) pituitary adenylate cyclase activating polypeptide on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanaesthetized rats. The flexor reflex was elicited by electrical stimulation applied subcutaneously to the sural nerve innervation area and recorded as electromyogram activity from ipsilateral hamstring muscles. Pituitary adenylate cyclase activating polypeptide(l-27) was administered over a wide dose range (10 ng to 10 mu g) and elicited a dose-dependent facilitation of the flexor reflex and did not depress the reflex at any dose. Furthermore, pituitary adenylate cyclase activating polypeptide did not inhibit the facilitation of the flexor reflex induced by repetitive stimulation of C-fibres. It is concluded that pituitary adenylate cyclase activating polypeptide had an excitatory effect on spinal cord function which may indicate a role for this peptide in nociceptive transmission and modulation. Moreover, in contrast to previous studies, we found no evidence suggesting that pituitary adenylate cyclase activating polypeptide exerts antinociceptive action at spinal level.

Age-dependent effects of muscle vibration and the Jendrassik maneuver on the patellar tendon reflex response

Objective: To explore possible effects of aging on the excitability of spinal reflexes. Design: Using a cross-sectional design, the influences of muscle vibration and the Jendrassik maneuver on patellar tendon reflex function were compared between 30 young adults and 15 older adults. Setting: Motor control research laboratory. Subjects: The young adults were volunteers of college age. The older adults (74.5 ± 4.14yr) were volunteers from the local community. All subjects were free of medications and neurological conditions that would affect normal neuromuscular responses. Main Outcome Measures: A force-time curve analysis of the patellar tendon reflex response was used to assess the inhibition and facilitation of spinal reflexes. In the experimental protocol to assess spinal reflex inhibition, 100Hz vibration was applied to the right quadriceps muscle. In another experimental protocol, spinal reflex facilitation was assessed using the Jendrassik maneuver. To perform the Jdnrassik maneuver, subjects were instructed to grasp their hands together and to pull as hard as possible while breathing normally. After a 2-second count, the tendon tap was delivered to the right leg and the subject was instructed to relax. In both experimental protocols, control patellar tendon reflexes were collected. Results: Analysis of variance for reflex peak force revealed a significant 30% reduction in the amount of vibration-induced reflex inhibition with increasing age, and a similar 33% reduction in the amount of Jendrassik maneuver facilitation observed for the older adults as compared with the younger adults. Conclusion: These results support the hypothesis that inhibitory and excitatory influences acting on the alpha motoneuron pool are different in young and older adults.

Spinal 5-HT2 receptor-mediated facilitation of pudendal nerve reflexes in the anaesthetized cat.

1. 5-Hydroxytryptamine (5-HT) is intimately associated with central sympathetic and somatic control of the lower urinary tract. The sympathetic and somatic innervation of the lower urinary tract is conveyed through efferent axons of the hypogastric and pudendal nerves, respectively. 2. The present study examined the effects of 2,5-dimethoxy-4-iodophenylisopropylamine (DOI), a 5-HT2 receptor subtype-selective agonist, on evoked potentials recorded from the central ends of the hypogastric and pudendal nerves in response to electrical stimulation of afferent fibres in the pelvic and pudendal nerves, respectively. Various spinalization paradigms were employed to localize the site of action. All cats were pretreated with xylamidine (1 mg kg-1), a peripherally-restricted 5-HT2 receptor antagonist. 3. In acute spinal cats, DOI (0.01-3 mg kg-1, i.v.) reliably produced dose-dependent increases in the pudendal nerve reflex (to 228 +/- 31% of control). These increases were reversed by the 5-HT2 receptor-selective antagonist, LY53857 (0.3-3 mg kg-1, i.v.). On the other hand, in spinally-intact cats, DOI produced no significant changes in the pudendal reflex. However, within minutes of spinalization of DOI-pretreated cats, a marked increase (to 221 +/- 16% of control) in the pudendal reflex was observed which could be reversed by LY53857. No significant effects were observed on hypogastric reflexes in either acute spinal or spinally-intact cats following DOI administration. No effects were seen in either spinally-intact or acute spinal animals when LY53857 was administered as the initial drug. 4. These results indicate that activation of spinal 5-HT2 receptors facilitates pudendal reflexes. In spinally-intact cats, it is hypothesized that DOI activates supraspinal pathways that mediate inhibition of the pudendal reflexes and counteracts the facilitatory effects of spinal 5-HT2 receptor activation.

Supraspinal influences on the facilitation of rat nociceptive reflexes induced by carrageenan monoarthritis

During hyperalgesia there is an enhancement of wind-up and the appearance of a novel wind-up of the A-fibre-mediated responses. We have examined if these phenomena are influenced by supraspinal mechanisms by analysing single motor unit activity in control and arthritic rats, either intact or acutely spinalised. Enhancement of the C-fibre wind-up and the novel A-fibre wind-up were only observed in the intact arthritic animals. We conclude that C-fibre wind-up is a spinal phenomenon, whereas the enhancement of the C-fibre wind-up and the novel A-fibre wind-up during arthritis depend also on supraspinal influences.

Impaired reflex responses to airway occlusion in the inspiratory muscles of asthmatic subjects.

Asthmatic subjects have an impaired capacity to activate the diaphragm during attempted maximal inspiratory efforts. Limb muscles require reflex facilitation to achieve maximal force. The reflex responses of inspiratory muscles to airway occlusion in asthmatic subjects were measured and compared with those in non-asthmatic control subjects. Nine healthy asthmatic subjects breathed at a constant inspiratory flow through a low resistance valve. Random inspirations were transiently occluded for 250 ms. Surface electromyographic activity (EMG) was recorded over the scalene muscles, parasternal intercostal muscles, and the lateral chest wall overlying the diaphragm. The asthmatic subjects were studied with and without bronchoconstriction. Responses were compared with data from a matched group of 12 control subjects. Compared with the reflex responses to airway occlusion in control subjects, the duration of the initial short latency inhibition of inspiratory muscles was prolonged by 50% in asthmatic subjects and the size of the subsequent excitation was reduced by 30%. Bronchoconstriction reduced the time to the peak of the excitatory response in asthmatic subjects, although the values remained longer than in the control subjects. This study reveals impaired reflex excitation of inspiratory motoneurones in asthmatic subjects which could contribute to the reduced ability of these subjects to drive the diaphragm during maximal volitional efforts.

Changes in nociceptive reflex facilitation during carrageenan-induced arthritis

Facilitation of neuronal responses induced by repetitive electrical stimulation of C-fibres (wind-up) is thought to be a substrate of hyperalgesia. There is little information on how these responses are in turn modified during hyperalgesia, and the extent to which hyperalgesic states also induce a facilitation of the neuronal responses mediated by A-fibres. The current study was undertaken in order to evaluate the effects of peripheral inflammation and stimulus presentation on the facilitation of nociceptive reflexes. Flexor reflexes, recorded as single motor units, were evoked in rats by cycles of low and high frequency electrical stimulation with pulse durations of 0.2, 0.5 and 2 ms. Responses were studied in control and inflammatory conditions, using the carrageenan-induced mono-arthritis model. The results show that the facilitation of late (C-fibre mediated) responses was proportional to the pulse duration of stimulation, as well as to the stimulation frequency. Facilitation was always higher when animals were subjected to inflammation. In inflammatory conditions, facilitation of reflexes was observed not only for late (C-fibre mediated) but also for early (A-fibre mediated) reflex responses. However, the facilitation of these early responses was not proportional to the intensity of stimulation. Thus, in arthritic animals, late (C-fibre mediated) flexion reflexes elicited from the skin, are facilitated and early (A-fibre mediated) reflexes are not only facilitated but, in addition, show a novel wind-up phenomenon.

5-HT3 and 5-HT4 receptor-mediated facilitation of the emptying phase of the peristaltic reflex in the marmoset isolated ileum.

1. The patterns of intestinal motility and the effect of an increase in intraluminal pressure were studied in vitro on segments obtained from the marmoset small intestine. 2. Segments obtained from the distal half of the marmoset small intestine exhibited segmentation, consisting of narrow annular contractions (lasting for 2-3 s) interposed between the relaxed segments of varying length. The subsequent contractions occurred slightly distal to the previous contraction, with ring-like contractions appearing to move in the aboral direction. Such segmentation was infrequent or absent in the segments obtained from the proximal half of the small intestine. An increase in intraluminal pressure inhibited segmentation and finally produced peristalsis in most of the tissues. 3. The influence of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on the threshold of the peristaltic reflex was investigated in the segments obtained from the distal half of the intestine after segmentation had subsided. The effect of drug application to the serosal surface was measured as a change in threshold pressure required to trigger the peristaltic reflex. A facilitation was defined in two ways (a) as a reduction in the threshold pressure required to trigger the reflex and (b) in those tissues that failed to respond with peristalsis on raising intraluminal pressure to the maximum attainable (1 kPa), as a reduction in threshold pressure compared to this value. 4. 5-HT (7.85 +/- 0.19), 5-methoxytryptamine (7.79 +/- 0.24), 5-carboxamidotryptamine (6.66 +/- 0.13) and 2-methyl-5-HT (6.24 +/- 0.16) caused a concentration related facilitation of the peristaltic reflex, the pD2 values (mean +/- s.e.mean) being shown in parentheses. 5. The concentration-response curves to both 5-HT and 5-methoxytryptamine were dextrally shifted in a surmountable manner in the presence of GR 113808 (30 nM). pD2 values for 5-HT and 5-methoxytryptamine were significantly decreased to 6.98 +/- 0.24 and 6.83 +/- 0.36 respectively in the presence of GR 113808 (30 nM). 6. In the presence of a high concentration of (10 microM) 5-methoxytryptamine the subsequent addition of 2-methyl-5-HT (3-10 microM) but not 5-methoxytryptamine (10 microM) facilitated peristalsis; the effect of 3 microM 2-methyl-5-HT was significantly decreased by 2 microM ondansetron. 7. It is concluded that the facilitation of the peristaltic reflex in the marmoset intestine induced by 5-HT at submicromolar concentrations involves a 5-HT4 receptor stimulation with an additional 5-HT3 receptor activation at higher concentrations.

Restoration of extensor excitability in the acute spinal cat by the 5-HT2 agonist DOI

1. The decerebrate cat preparation with an intact spinal cord is characterized by a high degree of excitability in extensor motoneuron pools, which is eliminated by acute spinalization. Subtype-specific agonists for serotonin (5-HT) were investigated in terms of their effectiveness in restoring the extensor excitability following spinalization. 2. Our hypothesis was that 5-HT2 receptors have the primary role in enhancement of extensor reflex excitability, whereas 5-HT1A and 5-HT1B/D receptors are relatively unimportant. Reflex excitability was assessed from the tonic levels of force and electromyographic (EMG) output from the ankle extensors medial gastrocnemius (MG) and soleus (SOL), and from the reflex forces in both these muscles generated by ramp-and-hold stretches of MG. 3. Before spinal transection, MG and SOL usually exhibited a small amount of tonic background EMG activity and force output. Ramp-and-hold stretch of MG generated a large-amplitude reflex response. Spinal transection at the level of T10 virtually abolished tonic background activity in both extensors and greatly attenuated the MG stretch reflex. Ventral topical application of the selective 5-HT2A/2C agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane hydrochloride (DOI) restored the amplitude of the MG stretch reflex in a dose-dependent fashion. However, a considerable portion of the DOI-mediated restoration of MG stretch reflex force was due to elevation of tonic background force levels above previous intact cord levels. 4. The DOI-induced increase in extensor tonic background excitability and facilitation of MG stretch reflex were reversed by ventral topical administration of the selective 5-HT2 antagonist ketanserin. No increase in extensor excitability was observed in spinalized preparations after administration of either the 5-HT1A agonist (+-)-8-hydroxy-dipropylaminotetralin hydrobromide or the 5-HT1B/1D agonist 7-trifluoromethyl-4-(4 methyl-1-piperazinyl)-pyrrolo[1,2- a]quinoxaline maleate. These data strongly suggest that the DOI-induced facilitation of extensor stretch reflex and tonic activity in spinalized preparations is mediated through an action on spinal 5-HT2 receptors. 5. One important difference between the actions of DOI in spinalized versus intact states was that the DOI-induced tonic and reflex forces in the spinalized state were subject to irregular oscillations. In contrast, DOI did not noticeably affect the smoothness of reflex force generation in the intact state. This discrepancy was probably due to the effects of clasp knife inhibition from muscular free nerve endings, which have potent reflex actions in the spinalized but not intact states. Thus DOI elevated excitability levels but did not alter the effects of spinalization on stretch reflex patterns.

The effects of isoflurane on repeated nociceptive stimuli (central temporal summation)

Central temporal summation of afferent nociceptive stimuli is involved in central hyperexcitability. This is assumed to be an important mechanism in the nociceptive system which is probably activated during surgery and trauma. The purpose of the present study was to investigate if isoflurane has a specific effect on central temporal summation in humans. Facilitation of the nociceptive reflex to repeated stimuli can be used to assess central summation in subjects unable to cooperate due to an anaesthetic procedure. The nociceptive reflex to single and repeated (5 pulses delivered at 2 Hz) electrical surface stimuli of the sural nerve were measured in 6 healthy volunteers anaesthetized with isoflurane. A reflex was defined as an EMG signal from the rectus and biceps femoris exceeding 20 μV for more than 10 msec in the 80–200 msec interval after the stimulus. The end-tidal isoflurane concentration was increased in steps of 0.25 vol% from 0.25 to 1.50 vol%. For each concentration the thresholds for the nociceptive reflex were determined as the current intensity that could just elicit a reflex response to single stimulations, and for the repeated stimulations as the current intensity that could just elicit a reflex response to the 4th and/or 5th stimuli in the train of 5 stimuli. The nociceptive reflex to single stimuli was depressed at isoflurane concentrations producing sedation or light anaesthesia (0.25–0.50 vol% end-tidal). In contrast, 2–4-fold higher isoflurane concentrations (1.00–1.50 vol% end-tidal) that normally produce surgical anaesthesia were required to depress the nociceptive reflex to repetitive stimuli. This indicates that central temporal summation in the nociceptive system is a potent mechanism, and that isoflurane has a weak potency for depressing temporal summation in humans. As such isoflurane alone is not adequate for inhibiting surgically evoked hyperexcitability.

Convergence of skin reflex and corticospinal effects in segmental and propriospinal pathways to forelimb motoneurones in the cat

The organization of facilitatory convergence from cutaneous afferents (Skin) and the corticospinal tract (pyramidal tract, Pyr) in pathways to forelimb motoneurones of mainly distal muscles was studied in anaesthetized cats by analysing postsynaptic potentials (PSPs), which were spatially facilitated by combinations of stimuli to the two sources at different time intervals. Conditioning Pyr volleys facilitated Skin-evoked PSPs of fixed (1.2-3.6 ms) central latencies (Skin PSPs), suggesting that disynaptic and polysynaptic skin reflex pathways are facilitated from the pyramidal tract. The shortest latencies (1.2-1.7 ms) of pyramidal facilitation suggested direct connection of pyramidal fibres with last order neurones of skin reflex pathways. Conditioning Skin volleys facilitated Pyr-evoked PSPs of fixed, mostly disynaptic latencies (1.0-2.5 ms; Pyr PSPs), suggesting that pyramido-motoneuronal pathways are facilitated from Skin at a premotoneuronal level. The shortest pathway from skin afferents to the premotor neurones appeared to be monosynaptic. Although Pyr and Skin volleys were mutually facilitating, the facilitation curve of Pyr PSPs and that of Skin PSPs were discontinuous to each other, with the peak facilitation at different Skin-Pyr volley intervals. Transection of the dorsal column (DC) at the C5/C6 border had little effect on the latencies or amplitudes evoked by maximal stimulation and the pyramidal facilitation of Skin PSPs. In contrast, the facilitation of Pyr PSPs by Skin stimulation was greatly decreased after the DC transection, and the facilitation curve of Pyr PSPs was continuous to that of Skin PSPs, with no separate peak. Latencies of Pyr PSPs ranged similarly to those in DC intact preparations. More rostral DC transection (C4/C5 border) reduced Skin-facilitated Pyr excitatory PSPs (EPSPs) less than C5/C6 lesions, suggesting that the C5 segment also contains neurones mediating Skin-facilitated Pyr EPSPs. The results show that convergence from skin afferents and the corticospinal tract occurs at premotor pathways of different cervical segments. We suggest that corticospinal facilitation of skin reflex occurs mostly in the brachial segments and Skin facilitation of cortico-motoneuronal effects takes place largely in the rostral cervical segments and partly in the brachial segments.

Click-rate induced facilitation of the acoustic reflex using constant number of pulses.

This investigation was designed to evaluate acoustic reflex thresholds at various repetition rates using a constant number of clicks (constant acoustic energy). Ipsilateral acoustic reflex thresholds were obtained from 19 left ears by presenting 300 clicks at the repetition rates of 50, 100, 150, 200 and 300/s. The results showed an improvement in the acoustic reflex thresholds with an increase in the repetition rates (rate integration). Thus for the test conditions used in the study, rate-induced facilitation of the acoustic reflex thresholds can be demonstrated even if the acoustic energy in the stimuli at various rates is held constant. Greater acoustic energy at higher repetition rates is unnecessary for such facilitation.

Role of Spinal Nitric Oxide in the Facilitation of the Micturition Reflex by Bladder Irritation

Purpose Nitric oxide (NO) is known to have an important transmitter function at peripheral synapses in the urogenital tract and has also been implicated in the transmission of nociceptive information in the spinal cord. The present study evaluated the role of NO in the central micturition reflex pathway. Materials and Methods We examined the effect of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, on micturition reflexes induced by continuous infusion of saline or 0.1 percent acetic acid (a noxious stimulus) into the bladder in urethane-anesthetized female rats. Bladder and external urethral sphincter function were monitored with a continuous cystometrogram (CMG) and electromyography (EMG). Results Intrathecal injection of L-NAME (0.01 to 1 micromole) did not significantly change the CMG or sphincter EMG during saline infusion. Infusion of acetic acid decreased the intercontraction interval (ICI), indicating a decrease in the volume threshold for inducing micturition. Subsequent intrathecal administration of L-NAME partially reversed the decreased ICI in a dose-dependent manner, but did not change the amplitude of bladder contractions: 0.01, 0.1 and 1 micromole of L-NAME produced increases of 25 percent, 31 percent and 56 percent in the ICI. D-NAME, the inactive stereoisomer had no effect. This effect of L-NAME was reversed by injection of L-arginine (2 micromole intrathecally) which, by itself, did not alter ICI during saline infusion or acetic acid infusion. Conclusions These results indicate that: (1) spinal NO containing pathways do not play a role in the normal micturition reflex, (2) NO is involved at the spinal level in the facilitation of the micturition reflex by nociceptive bladder afferents activated by noxious chemical irritation of the bladder.

Changes in Spinal Reflexes Preceding a Voluntary Movement in Young and Old Adults

Age-related differences in spinal excitability during response preparation were assessed by eliciting either a 50% H-reflex or an Achilles tendon reflex preceding the onset of a right plantar flexion contraction in 20 young adults (23.1 +/- 1.64 yrs) and 20 old adults (68.5 +/- 5.53 yrs). On each simple reaction time trial, the test reflex was elicited at a specific test interval during either the foreperiod or the response period. The foreperiod test intervals were 500, 600, 700, 800, 900, and 1000 msec after the presentation of the warning stimulus. The response period test intervals were 50, 100, 150, 200, 250, and 300 msec after the presentation of the response stimulus. Control reflexes were randomly elicited between the simple reaction time trials. Changes in reflex excitability were not observed during the foreperiod in either age group. During the response period, the percentage of H-reflex facilitation as compared to control H-reflexes was similar for the young (68%) and the old (61%) adults, but the magnitude of Achilles tendon reflex facilitation with respect to control reflex responses was greater in the young adults (74%) than in the old adults (38%). The time course of H- and tendon reflex facilitation was delayed in the old group during the response period. The results indicate that processes underlying the preparation and generation of a motor response are similar in young and old adults. However, these processes occur at a slower rate in old adults.

Auditory startle (audio-spinal) reaction in normal man: EMG responses and H reflex changes in antagonistic lower limb muscles

The audiospinal reaction (ASR) to a 30 msec tone of 90 dB has been studied in 66 seated healthy volunteers. Electromyographic bursts induced in trapezius (Tra), soleus (Sol) and tibialis anterior (TA) have been looked for. Facilitation of Sol H reflex has been measured in 21 subjects in terms of delays from delivery of the sound. Among the subjects, 11 had a stable TA H reflex whose facilitation was compared to that of Sol H. Effects of selective isometric voluntary contraction of either Sol or TA were assessed both on EMG responses and H reflex facilitation.At rest, only 36% of subjects exhibited a response in Sol at a mean latency of 123 msec and 39% in TA at a latency of 119 msec. Responses were seen in antagonist muscles in 74% of subjects. Incidence in Tra was 96%. During voluntary contraction, the results were not significantly changed either in the contracted muscle or its antagonist. H reflex facilitation of both TA and Sol started 50 msec after the sound to peak after 75–125 msec and returned to baseline values after 250 msec. Extent of Sol H reflex facilitation remained similar during voluntary contraction of Sol and TA. It was observed that EMG responses were more frequent in subjects with brisk reflexes but not necessarily in those who exhibited the largest H reflex facilitation. The results are in agreement with assumptions that ASR is mediated through reticulo-spinal pathways but do not support the view that it corresponds to a flexor reaction. In addition to providing quantitative data for comparisons in pathological cases, they suggest differences in the mode of activation of motoneurones by the motor cortex and subcortical nuclei.

New high affinity peptide antagonists to the spinal galanin receptor

1. The role of endogenous galanin in somatosensory processing has been studied with galanin receptor antagonists. The new galanin receptor ligands C7, M32, M38 and M40 bind with high affinity (Kd in nanomolar range) to spinal cord galanin receptors and possess oxidative stability as compared to earlier generations of peptide ligands. These peptides have been examined in the spinal flexor reflex model where exogenous galanin exhibited biphasic excitatory and inhibitory effects. 2. Intrathecal administration of C7 [galanin(1-13)-spantide] and M32 [galanin (1-13)-neuropeptide Y(25-36) amide] blocked facilitation of the nociceptive flexor reflex induced by 30 pmol intrathecal galanin in decerebrate, spinalized rats in a dose-dependent manner, thus behaving as antagonists of the galanin receptor. In contrast, M38[galanin(1-13)-(Ala-Leu)3-Ala amide] and M40 [galanin(1-13)-Pro-Pro-(Ala-Leu)2-Ala amide], exhibited only weak antagonism at high doses in this model. Moreover, lower doses of M40 potentiated galanin-induced reflex facilitation. C7 was neurotoxic at high doses in the rat spinal cord. 3. M32 and C7 were potent antagonists of galanin receptors in rat spinal cord, in correlation with their in vitro binding characteristics. In contrast, M38 and M40, despite their high in vitro affinity, exhibited only very weak antagonism. Moreover, M40 may also behave as a partial agonist. 4. Previous studies have shown that the galanin receptor may be heterogeneous. The discrepancy between in vitro binding and in vivo antagonistic potency of M38 and M40 may also suggest the presence of different galanin receptor subtypes within the rat spinal cord. However, other explanations for the discrepancy, such as differences in metabolic stability, diffusion rates and penetration to the site of action are also possible.

Facilitation of the human nociceptive reflex by stimulation of A beta-fibres in a secondary hyperalgesic area sustained by nociceptive input from the primary hyperalgesic area.

Hyperalgesia was induced in healthy volunteers by topical capsaicin applied on the dorsum of the foot within the receptive field of the sural nerve. Under presence of hyperalgesia different normally non-noxious conditioning stimuli were applied to the hyperalgesic area and the polysynaptic nociceptive spinal reflex and pain ratings were used to assess central excitability. The nociceptive reflex was measured in the knee extensor and flexor muscles evoked by electrical stimulation of the sural nerve trunk at an intensity of 1.5 times the initial reflex threshold (an intensity above the pain threshold). Thermal stimulation of the primary hyperalgesic area (re)established both on-going spontaneous pain and secondary hyperalgesia. Thus, increased nociceptive reflexes were recorded and increased pain intensity reported when A beta-fibres in the secondary hyperalgesic area were activated concurrently with the reflex testing after a non-noxious thermal stimulation of the primary hyperalgesic area. The A beta-fibre activation was achieved by continuous low-intensity electrical stimulation (40 Hz) that was initiated after on-going pain produced by the thermal stimulation had waned. The same measurement without prior thermal conditioning stimulation of the primary area resulted in no reflex facilitation, indicating rapid changes in the central excitability with existence of on-going nociceptive activity. This indicates that the development and maintenance of secondary hyperalgesia are dependent on sustained peripheral nociceptive activity. The study also shows that a central summation of nociceptive and non-nociceptive afferent activity can occur once secondary hyperalgesia is present.