Spinal Cord Excitability Research Articles

H-reflex and physiologic measures of ejaculation in men with spinal cord injury

Courtois F, Geoffrion R, Landry E, Bélanger M. H-reflex and physiologic measures of ejaculation in men with spinal cord injury. Arch Phys Med Rehabil 2004;85:910–8. Objective To investigate the various physiologic parameters characterizing and predicting ejaculation. Design Single case-control study. Setting A referred care center and university setting. Participants Two men with spinal cord injury (SCI) and 2 control subjects. Intervention Subjects were asked to self-stimulate with a Ferticare vibrator to induce ejaculation over 5 to 8 independent sessions. Main outcome measures Penile tumescence, blood pressure, heart rate, electromyographic activity of the bulbocavernosus muscles, abdominal muscles, soleus H-reflex, and occurrence of ejaculation. Results Changes on all measures were observed, with penile tumescence being more stable in control subjects. Blood pressure increased in both groups, whereas tachycardia was observed in controls and bradycardia in subjects with SCI. H-reflex dropped slightly in controls but increased in subjects with SCI. Muscular patterns differed on ejaculatory success or failure. Conclusions Physiologic changes on all measures can be observed in men with SCI as a function of ejaculation. Changes include hypertension and bradycardia, characteristic of hyperreflexia, and tachycardia in controls. The neural mechanisms underlying these patterns are discussed. H-reflex showed increased spinal cord excitability in subjects with SCI after ejaculation, which suggests spasticity. The results support investigation of the H-reflex to predict ejaculatory success or failure in men with SCI, along with specific analysis of muscular patterns.

Reproducible measurement of voluntary activation of human elbow flexors with motor cortical stimulation

Voluntary activation of muscle is commonly quantified by comparison of the extra force added by motor nerve stimulation during a contraction [superimposed twitch (SIT)] with that produced at rest by the same stimulus (resting twitch). An inability to achieve 100% voluntary activation implies that failure to produce maximal force output from the muscle must have occurred at a site at or above the level of the motoneurons. We have used cortical stimulation to quantify voluntary activation. Here, incomplete activation implies a failure at or above the level of motor cortical output. With cortical stimulation, it is inappropriate to compare extra force evoked during a contraction with the twitch evoked in resting muscle because motor cortical and spinal cord excitability both increase with activity. However, an appropriate "resting twitch" can be estimated. We previously estimated its amplitude by extrapolation of the linear relation between SIT amplitude and voluntary torque calculated from 35 contractions of >50% maximum (Todd G, Taylor JL, and Gandevia SC. J Physiol 551: 661-671, 2003). In this study, we improved the utility of this method to enable evaluation of voluntary activation when it may be changing over time, such as during the development of fatigue, or in patients who may be unable to perform large numbers of contractions. We have reduced the number of contractions required to only three. Estimation of the resting twitch from three contractions was reliable over time with low variability. Furthermore, its reliability and variability were similar to the resting twitch estimated from 30 contractions and to that evoked by conventional motor nerve stimulation.

Interaction between repetitive stimulation of the sciatic nerve and functional ablation of cerebellar nucleus interpositus in the rat

It is established that cerebellar nuclei exert a significant effect on the excitability of spinal neurons. However, their output is heterogeneous. Conditioning trains of dentate nucleus stimuli are known to modify the post-synaptic potentials evoked in motoneurons by stimulation of group Ia and Ib afferents in appropriate peripheral nerves. The role of the interpositus nucleus in the modulation of the excitability of rat spinal cord remains unclear. We investigated the interactions between tetrodotoxin (TTX)-induced inactivation of the interpositus cerebellar nuclei and repetitive electrical stimulation of the ipsilateral sciatic nerve (proximal segment) in the anesthetized rat. TTX (10 microM) was administered in cerebellar nuclei by the technique of microdialysis (coordinates of the extremity of the guide related to bregma: AP: -11.6, L: +2.3, V: -4.6). Peripheral stimulation consisted of trains of electric stimuli at a rate of 10 Hz, which were repeated every second during 1 hour. Stimulus intensity was adjusted to produce constant somatosensory evoked potentials. H-reflex, F-wave and M responses of the plantaris muscles were analysed ipsilaterally. H-reflex recruitment curve, Hmax/Mmax ratios, F-wave persistence and mean F/mean M ratios were studied. Functional blockade of cerebellar interpositus nucleus reduced the slope of H-reflex recruitment curve without affecting the Hmax/Mmax ratio, and depressed both F-waves persistence and mean F/mean M ratios. Concomitant repetitive stimulation of the sciatic nerve counteracted the depression of the H-reflex recruitment curve, without interacting with F-waves depression. Our results (1) show that TTX-sensitive sodium channels in cerebellar nucleus interpositus modulate the H-reflex recruitment, and (2) reveal an interaction between TTX-sensitive sodium channels in cerebellar nuclei and afferent repetitive activity not described so far.

Remote Facilitation of Soleus H-reflex Induced by Clenching on Occlusal Stabilization Appliances

Purpose : The purpose of this study was to examine the change in spinal cord excitability in a leg muscle during maximal voluntary clenching on a stabilization appliance.Materials and Methods : The H reflex of the soleus muscle was elicited in five healthy male volunteers by electrical stimulation of the tibial nerve under the following five dental occlusal conditions : mandibular rest position (RP : control), maximum voluntary clenching in the intercuspal position (IP), maximum voluntary clenching on a hard acrylic stabilization appliance (H-SA), maximum voluntary clenching on a soft stabilization appliance (S-SA) and maximum voluntary clenching on a very soft stabilization appliance (VS-SA).Results : The soleus H reflex modulations in the IP, H-SA, S-SA and VS-SA conditions were 117.6%, 119.5%, 126.2% and 133.6%, respectively. There was a significant difference between IP and S-SA, and IP and VS-SA (p=0.0001-0.0226) ; however, there was no significant difference between IP and H-SA (p=0.3412-0.9940). Significant positive correlations between the magnitude of the soleus H reflex and the masseter electromyogram activity were found in each subject (r=0.670-0.862, p<0.05).Conclusion : This study demonstrated that the spinal cord excitability in the motor pathway of a leg muscle was considerably raised during clenching on a soft stabilization appliance compared to a hard stabilization appliance, suggesting that a powerful biting action on a resilient intraoral appliance strongly influences the motor system in humans.

Remote effects of self-paced teeth clenching on the excitability of hand motor area.

We studied remote effects of teeth clenching on motor cortical and spinal cord excitability using transcranial magnetic stimulation (TMS), brainstem electrical stimulation (BES), and ulnar nerve stimulation (F-wave) in eight normal volunteers. The TMS, BES, and ulnar nerve stimulation at the wrist were given at different intervals (0-200 ms) after the onset of masseter contraction. Surface electromyographic responses were recorded from the first dorsal interosseous muscle. Responses at different intervals were compared with the response elicited when the subject made no teeth clenching (control response). In TMS, conditioned responses (during teeth clenching) were significantly larger than the control at all intervals. In contrast, in BES and F-waves, conditioned responses were not larger than the control at an early phase (intervals shorter than 50 ms), whereas they were larger than the control at later intervals (longer than 50 ms). These results suggest that facilitation occurs in the hand motor area at the early phase of teeth clenching, and spinal facilitation dominates at its late phase. This time course of facilitation may indicate that the motor cortex must regulate hand muscles finely at the early phase of teeth clenching, and spinal cord may stabilize them firmly at the late phase. The excitability changes of the hand motor area may be in parallel with that of the masseter motor area which reflects the pattern of masseter contraction when the subject activates the masseter muscle phasically at the early phase and sustains that contraction at the late phase.

State dependent excitability changes of spinal flexor reflex in patients with restless legs syndrome secondary to chronic renal failure

Objective: Periodic limb movement in sleep (PLMS) is a common dysfunction of motor control during sleep, occurring either in isolation or associated with a variety of neurological disorders including restless legs syndrome (RLS). Although the PLMS generators have not been established, their occurrence in patients with spinal cord injury and their clinical resemblance to the spinal cord flexor withdrawal reflex (FR) suggest that PLMS may originate in the circuitry that mediates the FR. The significantly increased spinal cord excitability noted in primary RLS/PLMS patients may play an important role in the pathophysiology of primary RLS. The aim of this study is to establish whether the enhanced spinal cord excitability, which is represented by a lower threshold and/or greater spatial spread of the FR, is also true for the RLS/PLMS patients whose RLS is secondary to chronic renal failure (CRF). Methods: Twenty patients with RLS/PLMS secondary to CRF have been compared with matched controls according to the state dependent changes in FR excitability. All patients met the diagnostic criteria for RLS and PLMS. They had CRF for 5.2±3.5 years, and were under the hemodialysis treatment. Twenty healthy, age and sex matched subjects were tested as controls. The electrophysiological testing of the FR was performed during wakefulness (9:30–10:30 p.m.) and sleep (beginning of stage II, the first sleep cycle). Results: A significant increase in FR excitability was found in RLS/PLMS patients with CRF. This abnormality was prominent during sleep, which was also true for the primary RLS. Conclusions: Our results suggest that similar neuronal pathways are involved in primary and secondary RLS/PLMS patients. Our results also support that RLS/PLMS and FR share a common spinal mechanism.

Comparison of the effect of intrathecal endomorphin-1 and endomorphin-2 on spinal cord excitability in rats

We examined and compared the effects of intrathecal (i.t.) endomorphin-1 and endomorphin-2 on the nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats. I.t. endomorphin-1 and -2 induced a dose-dependent depression of the flexor reflex with an initial brief facilitatory effect. The magnitude of reflex facilitation and depression was similar between endomorphin-1 and -2, but the duration of depression was significantly longer for endomorphin-1 than endomorphin-2. The results suggested that the spinal antinociceptive effects of endomorphin-1 and -2 are similar, with endomorphin-1 being more resistant to enzymatic degradation.

Modulation of spinal cord excitability by subthreshold repetitive transcranial magnetic stimulation of the primary motor cortex in humans.

Repetitive transcranial magnetic stimulation (rTMS) allows the modulation of intra-cortical excitability and may therefore affect the descending control of spinal excitability. We applied rTMS at subthreshold intensity and 1 Hz frequency for 10 min to the left primary motor cortex representation of the flexor carpi radialis muscle (FCR) in 10 subjects and assessed the H and M responses to median nerve stimulation before and after the rTMS. Following rTMS, H wave thresholds significantly reduced by approximately 20%. Maximal H but not M wave amplitude significantly increased over the baseline, so that H/M amplitude ratio was increased by 41%. Sham stimulation did not induce any noticeable change in M or H waves. Slow rTMS might facilitate monosynaptic spinal cord reflexes by inhibiting the cortico-spinal projections modulating spinal excitability.

Transient inhibition of the human motor cortex by capsaicin-induced pain. A study with transcranial magnetic stimulation

Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the left motor cortex were recorded from the right first dorsal interosseous (FDI), abductor pollicis brevis (APB), abductor digiti minimi (ADM), flexor carpi radialis (FCR), extensor carpi radialis (ECR) in 17 normal subjects, before and after painful application of capsaicin on the skin overlying the right FDI and FCR muscles. The amplitude of MEPs from the FDI and FCR was significantly reduced from 20 to 30 min after the application of capsaicin over the FDI and FCR muscles, respectively, then progressively returned to the basal values. A similar trend of MEPs inhibition was observed for APB and FCR muscles, but this reduction was not significant. Indices of peripheral nerve (M-wave) and spinal cord excitability (F and H waves) did not change throughout the experiments. Motor cortex inhibition induced by tonic cutaneous pain is maximal to muscles adjacent to the painful area. This inhibition may be due to the activation of the C fibres which mediate ‘slow’ nociception and might be important to alert subject to possible phasic nociceptive events that may occur close to the painful area.

Endogenous galanin is required for the full expression of central sensitization following peripheral nerve injury.

The neuropeptide galanin is known to be involved in nociceptive sensory processing in the spinal cord. We have attempted to better characterise the function of endogenous galanin in nociceptive signalling by examining a mouse strain carrying a loss of function mutation in the galanin gene (gal-/-). Galanin expression is significantly up-regulated following damage to a peripheral nerve. To address what effect this up-regulation has on spinal cord excitability we have examined wild type (gal+/+) and gal-/- mice 3 days after complete transection of the sciatic nerve using an electrophysiological paradigm, the flexor withdrawal reflex. We demonstrate that the up-regulation of galanin has no direct effect on basal spinal excitability after nerve injury. However, galanin is shown to be a crucial neuromodulator involved in the development of the central sensitization as both windup and the facilitation of spinal reflexes following conditioning stimulation are significantly impaired in gal-/- mice following peripheral nerve injury.

Modulation of spinal excitability during observation of hand actions in humans.

There is growing evidence that observation of actions performed by other individuals activates observer's cortical motor areas. This matching of observed actions on the observer's motor repertoire could be at the basis of action recognition. Here we investigated if action observation, in addition to cortical motor areas, involves also low level motor structures mimicking the observed actions as if they were performed by the observer. Spinal cord excitability was tested by eliciting the H-reflex in a finger flexor muscle (flexor digitorum superficialis) in humans looking at goal-directed hand actions presented on a TV screen. We found that, in the absence of any detectable muscle activity, there was in the observers a significant modulation of the monosynaptic reflex size, specifically related to the different phases of the observed movement. The recorded H-reflex rapidly increased in size during hand opening, it was depressed during hand closing and quickly recovered during object lifting. This modulation pattern is, however, opposite to that occurring when the recorded muscles are actually executing the observed action [Lemon et al. (1995) J. Neurosci., 15, 6145-56]. Considering that, when investigated at cortical level the modulation pattern of corticospinal excitability replicates the observed movements [Fadiga et al. (1995) J. Neurophysiol., 73, 2608-2611], this spinal 'inverted mirror' behaviour might be finalised to prevent the overt replica of the seen action.

Changes in spinal cord excitability in patients affected by ulnar neuropathy.

To evaluate whether ulnar neuropathy could induce changes in spinal cord and motor cortex excitability and therefore predispose to development of focal dystonia. A high incidence of ulnar neuropathy has been observed in patients with musician's cramp. Polygraphic electromyograph recordings in patients with entrapment of the ulnar nerve at the elbow have demonstrated long-duration bursts of co-contraction in antagonistic muscles, similar to those observed in focal dystonia. All control subjects and 12 patients with ulnar neuropathy underwent an electrophysiologic protocol consisting of polygraphic recordings of a repetitive tapping task of the fourth finger, assessment of reciprocal inhibition in forearm muscles, and investigation of motor cortex excitability after paired transcranial magnetic stimulation. Eleven of 12 patients with ulnar neuropathy showed a loss of alternation and of well-formed bursts in both flexor and extensor muscles. Evaluation of reciprocal inhibition in these patients revealed a reduction in the amount of inhibition in the disynaptic and presynaptic phases. None of the patients presented with a clinically evident dystonia of the upper limb. The study of intracortical excitability after paired shocks did not reveal any difference in the amount of intracortical inhibition and facilitation compared with the control group. A peripheral nerve injury can induce a rearrangement of reciprocal inhibition circuits at the spinal cord level. These changes might predispose to the development of a focal dystonia. However, it is likely that another, yet unknown, factor is required to alter the intracortical circuits and produce a clinically evident dystonia.

Brief and prolonged effects of Lissauer tract stimulation on dorsal horn cells

Increased excitability of dorsal horn neurones may play a critical role in producing some pain states and there is evidence that the excitability of neurones lying throughout the dorsal horn is subject to regulation by cells in its most superficial laminae. This paper examines the effect on dorsal horn cell receptive fields and excitability of the specific activation of Lissauer's tract, a tract containing propriospinal axons which arise from cells in the substantia gelatinosa and which project to the substantia of neighbouring spinal segments. Experiments were carried out on anaesthetised spinal rats in the L3-4 spinal segments with microelectrode stimulation on the surface of the Lissauer tract (LT) and microelectrode recording of single cells or small groups of cells that responded to gentle brushing on the skin. Single shocks or brief trains of low-level stimuli to the LT produced a characteristic long-latency dorsal root potential (DRP) on the L3 dorsal root and a brief burst of firing in superficial cells with no stimulation of primary afferents. Generally, this was accompanied by no excitation of deeper dorsal horn cells but commonly by a period of inhibition, often followed by facilitation. We then turned to the effect of long periods (30–90min) of continual LT stimulation because we had seen hints of prolonged facilitation of the deeper cells after periods of such stimulation. Trains of 5 stimuli separated by 2ms and repeated every 200ms were used with individual pulses of 200μs duration and less than 10μA amplitude. This resulted in a shift of the effect on deep cells from primarily inhibition to mainly facilitation. We then examined in detail the effect of these long periods of LT stimulation on the size of receptive fields (RFs) of dorsal horn cells first on single units and then by repeated mapping of the RFs of small groups of cells. Control periods of 60min with no LT stimulation produced no significant RF changes but 30, 60 or 90min of LT stimulation produced successively greater expansions of RFs. When the LT stimulus was turned off after 1h, the RFs remained expanded for at least 2h. The spike height of these cells remained unchanged. The effect was not influenced by the NMDA antagonist MK801 but was imitated by the GABAA antagonist picrotoxin. It is concluded that the prolonged expansion of RFs could not be produced by modulation of descending control since the animals had spinal transections. Neither was it dependent on an NMDA-sensitive mechanism. With these data it is not possible to conclude whether the mechanism is pre-synaptic, post-synaptic or both. It is proposed that the most likely explanation is a decrease in the normal tonic inhibition operated in part by a GABA dependent mechanism. This phenomenon may play a role in prolonged pathological states of increased spinal cord excitability.

Excitability of spinal cord and gracile nucleus neurons in rats with chronically injured sciatic nerve examined by c-fos expression

Low-threshold sensory pathways have been suggested to have an important role in the formation and maintenance of sensory abnormalities which are observed after peripheral nerve injury. Fos-like immunoreactive (Fos-LI) neurons are expressed in spinal cord laminae III–IV and the gracile nucleus by electrically stimulating the injured nerves at Aβ strength after sciatic nerve transection in rats. This suggests that the excitability of these neurons is increased by nerve injury. In this study, we investigated which receptors are involved in the regulation of the increased excitability in spinal and gracile nucleus neurons. The sciatic nerve of Sprague–Dawley rats (150 g) was transected 7 days before the experiment day. The rats were administered morphine, muscimol, baclofen, MK-801, CNQX, N G-nitro- l-arginine methyl ester hydrochloride ( l-NAME) or clonidine i.p., and then electrically stimulated at 0.1 mA to the proximal region to the nerve injury site under urethane anesthesia. Two hours after the stimulation, Fos-LI expression was increased in the spinal cord dorsal horn and the gracile nucleus in control rats. Baclofen inhibited the Fos-LI expression both in the spinal cord and the gracile nucleus. Morphine inhibited only the Fos-LI expression in the posterior cutaneous (PC) nerve territory of laminae I–II, but not in the sciatic nerve (SC) territory, laminae III–IV nor the gracile nucleus. MK-801 had an inhibitory but complicated effect in laminae I–II and the gracile nucleus. The other drugs were not effective on Fos-LI expression. It is suggested that the GABA B receptor has a pivotal role in the regulation of Fos-LI expression after electrical stimulation to the injured low-threshold sensory fibers, and other receptors have little effect on the Fos-LI expression.

The effects of desflurane on the nervous system: from spinal cord to muscles.

Monitoring of motor pathways via muscle contraction recording is sensitive to anesthetics, particularly volatile anesthetics. However, the specific action sites of these anesthetics on the spinal cord and the peripheral nervous system are not well known in humans. Therefore, we studied proximal and distal motor and sensory nerve conduction, neuromuscular junction transmission, and spinal cord excitability (H/M amplitude ratio and F-wave amplitude and persistency) using standard neurophysiological techniques in 10 patients who underwent orthopedic surgery. Muscle potentials evoked by spinal cord stimulation were recorded in five additional patients. Desflurane was introduced to achieve end-tidal concentration of 3.7% and 7.4%, in 50% O2/N2O and in 100% O2. Measurements were obtained before desflurane administration and 20 min after obtaining a stable level of each concentration. Peripheral nerve conduction and neuromuscular function were not significantly affected by desflurane. However, spinal cord excitability was significantly decreased by desflurane administration (H/M ratio 37% +/- 9%, 12% +/- 5%, 7% +/- 4% at desflurane concentration 0.0%, 3.7%, and 7.4% in 100% O2, respectively). Muscle potentials evoked by spinal cord stimulation were abolished by desflurane. These data rule out the possibility that desflurane specifically alters peripheral nerve conduction or synapse transmission at the neuromuscular junction. They demonstrate that desflurane acts preferentially at the level of the spinal motoneuron. We used neurophysiological techniques to assess the effects of desflurane on spinal cord conduction and excitability, motor and sensory peripheral nerve conduction, and neuromuscular transmission. Our data demonstrate that desflurane acts preferentially at the level of the spinal motoneuron, providing useful information for neurophysiological monitoring and immobilization during surgery and for minimum alveolar anesthetic concentration definition.

Regulation of excitability of spinal cord and gracile nucleus neurons in the chronically injured sciatic nerve

Regulation of excitability of spinal cord and gracile nucleus neurons in the chronically injured sciatic nerve

Temporal summation of C-fiber afferent inputs: competition between facilitatory and inhibitory effects on C-fiber reflex in the rat.

Long-lasting facilitations of spinal nociceptive reflexes resulting from temporal summation of nociceptive inputs have been described on many occasions in spinal, nonanesthetized rats. Because noxious inputs also trigger powerful descending inhibitory controls, we investigated this phenomenon in intact, halothane-anesthetized rats and compared our results with those obtained in other preparations. The effects of temporal summation of nociceptive inputs were found to be very much dependent on the type of preparation. Electromyographic responses elicited by single square-wave electrical shocks (2 ms, 0.16 Hz) applied within the territory of the sural nerve were recorded in the rat from the ipsilateral biceps femoris. The excitability of the C-fiber reflex recorded at 1.5 times the threshold (T) was tested after 20 s of electrical conditioning stimuli (2 ms, 1 Hz) within the sural nerve territory. During the conditioning procedure, the C-fiber reflex was facilitated (wind-up) in a stimulus-dependent fashion in intact, anesthetized animals during the application of the first seven conditioning stimuli; thereafter, the magnitude of the responses reached a plateau and then decreased. Such a wind-up phenomenon was seen only when the frequency of stimulation was 0.5 Hz or higher. In spinal, unanesthetized rats, the wind-up phenomenon occurred as a monotonic accelerating function that was obvious during the whole conditioning period. An intermediate picture was observed in the nonanesthetized rat whose brain was transected at the level of the obex, but the effects of conditioning were profoundly attenuated when such a preparation was anesthetized. In intact, anesthetized animals the reflex was inhibited in a stimulus-dependent manner during the postconditioning period. These effects were not dependent on the frequency of the conditioning stimulus. Such inhibitions were blocked completely by transection at the level of the obex, and in nonanesthetized rats were then replaced by a facilitation. A similar long-lasting facilitation was seen in nonanesthetized, spinal rats. It is concluded that, in intact rats, an inhibitory mechanism counteracts the long-lasting increase of excitability of the flexor reflex seen in spinal animals after high-intensity, repetitive stimulation of C-fibers. It is suggested that supraspinally mediated inhibitions also participate in long term changes in spinal cord excitability after noxious stimulation.

The effect of naturally occurring fragments of galanin message-associated peptide on spinal cord excitability in rats

Galanin message-associated peptide (GMAP), a 60 amino acid fragment of galanin precursor protein, is present in dorsal root ganglion cells and upon intrathecal (i.t.) administration influences the spinal nociceptive flexor reflex in rat in a complex manner. The present study assessed the effects on spinal cord excitability of N-terminal fragment GMAP (1–30) and C-terminal fragments GMAP (34–60) or GMAP (35–60), which were formed from GMAP following enzymatic degradation. The effect of the fragments was compared with the effects of the complete peptide sequence. The GMAP fragments slightly facilitated the flexor reflex and dose-dependently blocked hyperexcitability following C-fiber conditioning stimulation. The potency of the blocking effect of GMAP(1–30) was comparable to GMAP(1–60) and was one order of magnitude higher than the potency of the C-terminal fragments. The results indicated that both naturally formed N- and C-terminal fragments of GMAP are pharmacologically active and produce effects which are similar to the full peptide sequence.

Signal changes in the spinal cord of the rat after injection of formalin into the hindpaw: characterization using functional magnetic resonance imaging.

Changes in metabolism and local circulation occur in the spinal cord during peripheral noxious stimulation. Evidence is presented that this stimulation also causes signal intensity alterations in functional magnetic resonance images of the spinal cord during formalin-induced pain. These results indicate the potential of functional magnetic resonance imaging in assessing noninvasively the extent and intensity of spinal cord excitation in this well characterized pain model. Therefore, the aim of this study was to establish functional magnetic resonance imaging as a noninvasive method to characterize temporal changes in the spinal cord after a single injection of 50 microl of formalin subcutaneously into the hindpaw of the anesthetized rat. This challenge produced a biphasic licking activity in the freely moving conscious animal. Images of the spinal cord were acquired within 2 min, enabling monitoring of the site and the temporal evolution of the signal changes during the development of formalin-induced hyperalgesia without the need of any surgical procedure. The time course of changes in the spinal cord functional image in the isoflurane-anesthetized animal was similar to that obtained from behavioral experiments. Also, comparable physiological data, control experiments, and the inhibition of a response through application of the local anesthetic agent lidocaine indicate that the signal changes observed after formalin injection were specifically related to excitability changes in the relevant segments of the lumbar spinal cord. This approach could be useful to characterize different models of pain and hyperalgesia and, more importantly, to evaluate effects of analgesic drugs.

Spinal Cord Motoneuron Excitability during Isoflurane and Nitrous Oxide Anesthesia

Recent evidence suggests that the spinal cord is an important site of anesthesia that is necessary for surgical immobility, but the specific effect of anesthetics within the spinal cord is unclear. This study assessed the effect of isoflurane and nitrous oxide on spinal motoneuron excitability by monitoring the H-reflex and the F wave. Eight adult patients, categorized as American Society of Anesthesiologists physical status 1 or 2, who were undergoing elective orthopaedic surgery were anesthetized with 0.6, 0.8, 1.0, and 1.2 times the estimated minimum alveolar concentration (MAC) of isoflurane. Nitrous oxide was added in graded concentrations of 30%, 50%, and 70%, whereas the isoflurane concentration was decreased to maintain a total MAC of 1. The H-reflex of the soleus muscle and the F wave of the abductor hallucis muscle were measured before anesthesia and 15 min after each change of anesthetic concentration. Four or more trials of the H-reflex and 18 trials of the F wave were recorded at each concentration of anesthesia. The effect of the anesthetics on the H-reflex and F wave was analyzed using. Dunnett's test. H-reflex amplitude was decreased to 48.4 +/- 18.6% of preanesthesia level at 0.6 MAC isoflurane and to 33.8 +/- 19.1% when isoflurane concentration increased from 0.6 MAC to 1.2 MAC. F wave amplitude and persistence decreased to 52.2 +/- 33.6% and 44.4 +/- 26% of baseline at 0.6 MAC isoflurane, and to 33.8 +/- 26% and 21.7 +/- 22.8% at 1.2 MAC isoflurane. Isoflurane plus nitrous oxide (total 1 MAC) decreased H-reflex amplitude to 30.4-33.3% and decreased F wave persistence to 42.8-56.3% of baseline. Both isoflurane alone and isoflurane plus nitrous oxide decrease H-reflex and F-wave amplitude and F-wave persistence. These effects suggest that isoflurane and nitrous oxide decrease motoneuronal excitability in the human spinal cord. This may play an important role in producing surgical immobility.