An evaluation of a healthy participant laboratory model of epidural hyperthermia: a physiological study.

BACKGROUND: Hyperthermia complicates 21% of cases of intrapartum epidural analgesia, but the mechanism is unclear. One hypothesis is that blockade of cholinergic sympathetic nerves prevents active vasodilation and sweating, thus limiting heat loss. Because labour increases heat production, this could create a situation in which heat production exceeds loss, causing body temperature to rise. This physiological study tested a novel laboratory model of epidural-related hyperthermia, using exercise to simulate the increased heat production of labour and surface insulation to simulate the effect of epidural analgesia. METHODS: Twelve healthy non-pregnant participants (six female) cycled an ergometer for two hours at 20 Watts (W) on two occasions: once with surface insulation (intervention) and once without (control). Core temperature, skin temperature (eight sites), and heat loss (eight sites) were recorded. Mean body temperature and heat production were calculated. Values are mean (SD). RESULTS: Exercise increased heat production on both visits (intervention 38 (18) W; control 37 (31) W; P = 0.94). Total heat loss was less on the intervention visit (intervention 115 (19) W; control 129 (23) W; P = 0.002). Core temperature increased on both visits (intervention 0.21 (0.37)°C; control 0.19 (0.27)°C; P < 0.001). The increase in mean body temperature was greater on the intervention visit (intervention 0.47 (0.41)°C; control 0.25 (0.19)°C; P = 0.007). CONCLUSIONS: This laboratory model predicts that labour epidural analgesia limits heat loss by >14 W. Once the model is validated, it could be used to test the efficacy of potential interventions to prevent and treat epidural-related maternal hyperthermia.

Heat stress associated with aerosol PPE and its impact.

BACKGROUND: Aerosol personal protective equipment (PPE) is subjectively reported to negatively impact healthcare workers' performance and well-being, but this has not been assessed objectively. AIMS: This randomized controlled crossover study aimed to quantify the heat stress associated with aerosol PPE and to investigate its impact upon mood, cognitive and motor function, and task performance. METHODS: Sixteen healthy, young, lean participants (eight males) undertook an exercise protocol, which simulated the metabolic expenditure of hospital work: once wearing aerosol PPE (PPE visit) and once wearing standard surgical attire (control visit). Participants walked on a treadmill for 2 h followed by 30-min rest. Core temperature, heart rate, urine specific gravity, weight, grip strength, mood (Bond-Lader scale) and task performance (Intubation of a Manikin) were recorded. Values are between-visit mean (standard deviation) differences. RESULTS: On the PPE visit core temperature (+0.2 (0.3)°C; P < 0.01), heart rate (+12 (13) bpm; P < 0.001), urine specific gravity (+0.003 (0.005); P < 0.05) and intubation task time (+50 (81) s; P < 0.01) were greater than on the control visit; and alertness (-14 (21) mm; P < 0.001), contentment (-14 (15) mm; P < 0.001) and grip strength (-4 (4) N; P < 0.01) were less. CONCLUSIONS: This study demonstrates that wearing aerosol PPE in a simulated hospital environment results in heat exhaustion and has a negative impact upon mood, motor function, and task performance. Whilst wearing PPE is important to prevent disease transmission, strategies should be developed to limit its impact upon healthcare workers' performance and well-being.

Reliability of high-density surface electromyography for assessing characteristics of the thoracic erector spinae during static and dynamic tasks.

PURPOSE: To establish intra- and inter-session reliability of high-density surface electromyography (HDEMG)-derived parameters from the thoracic erector spinae (ES) during static and dynamic goal-directed voluntary movements of the trunk, and during functional reaching tasks. METHODS: Twenty participants performed: 1) static trunk extension, 2) dynamic trunk forward and lateral flexion, and 3) multidirectional functional reaching tasks on two occasions separated by 7.5 ± 1.2 days. Muscle activity was recorded bilaterally from the thoracic ES. Root mean square (RMS), coordinates of the barycentre, mean frequency (MNF), and entropy were derived from the HDEMG signals. Reliability was determined with intraclass correlation coefficient (ICC), coefficient of variation, and standard error of measurement. RESULTS: Good-to-excellent intra-session reliability was found for all parameters and tasks (ICC: 0.79-0.99), whereas inter-session reliability varied across tasks. Static tasks demonstrated higher reliability in most parameters compared to functional and dynamic tasks. Absolute RMS and MNF showed the highest overall reliability across tasks (ICC: 0.66-0.98), while reliability of the barycentre was influenced by the direction of the movements. CONCLUSION: RMS and MNF derived from HDEMG show consistent inter-session reliability in goal-directed voluntary movements of the trunk and reaching tasks, whereas the measures of the barycentre and entropy demonstrate task-dependent reliability.

A mechanistic study of the tremor associated with epidural anaesthesia for intrapartum caesarean delivery.

BACKGROUND: It is not known if the tremor associated with an epidural top-up dose for intrapartum caesarean delivery is thermoregulatory shivering. A tremor is only shivering if it has the same frequency profile as cold stress-induced shivering. Thermoregulatory shivering is a response to a reduction in actual body temperature, whereas non-thermoregulatory shivering may be triggered by a reduction in sensed body temperature. This mechanistic study aimed to compare: 1. the frequency profiles of epidural top-up tremor and cold stress-induced shivering; and 2. body temperature (actual and sensed) before epidural top-up and at the onset of tremor. METHODS: Twenty obstetric patients received an epidural top-up for intrapartum caesarean delivery and 20 non-pregnant female volunteers underwent a cold stress. Tremor, surface electromyography, core temperature, skin temperature (seven sites) and temperature sensation votes (a bipolar visual analog score ranging from -50 to +50 mm) were recorded. RESULTS: The mean (SD) primary oscillation (9.9 (1.9) Hz) frequency of epidural top-up tremor did not differ from that of cold stress-induced shivering (9.0 (1.6) Hz; P=0.194), but the mean (SD) burst frequency was slower (6.1 (1.2) × 10-2 Hz vs 6.9 (0.7) × 10-2 Hz, respectively; P=0.046). Before the epidural top-up dose, the mean (SD) core temperature was 37.6 (0.6) °C. Between the epidural top-up dose and the onset of tremor the mean (SD) core temperature did not change (-0.1 (0.1) °C; P=0.126), the mean (SD) skin temperature increased (+0.4 (0.4) °C; P=0.002) and the mean (SD) temperature sensation votes decreased (-12 (16) mm; P=0.012). CONCLUSION: These results suggest that epidural top-up tremor is a form of non-thermoregulatory shivering triggered by a reduction in sensed body temperature.

Diffusion tensor imaging reveals changes in microstructural integrity along compressed nerve roots that correlate with chronic pain symptoms and motor deficiencies in elderly stenosis patients.

Age-related degenerative changes in the lumbar spine frequently result in nerve root compression causing severe pain and disability. Given the increasing incidence of lumbar spinal disorders in the aging population and the discrepancies between the use of current diagnostic imaging tools and clinical symptoms, novel methods of nerve root assessment are needed. We investigated elderly patients with stenosis at L4-L5 or L5-S1 levels. Diffusion tensor imaging (DTI) was used to quantify microstructure in compressed L5 nerve roots and investigate relationships to clinical symptoms and motor neurophysiology. DTI metrics (i.e. FA, MD, AD and RD) were measured at proximal, mid and distal segments along compressed (i.e. L5) and intact (i.e. L4 or S1) nerve roots. FA was significantly reduced in compressed nerve roots and MD, AD and RD were significantly elevated in the most proximal segment of the nerve root studied. FA was significantly correlated with electrophysiological measures of root function: minimum F-wave latency and peripheral motor conduction time (PMCT). In addition, FA along the compressed root also correlated with leg pain and depression score. There was also a relationship between RD and anxiety, leg pain and disability score and AD correlated with depression score. Taken together, these data show that DTI metrics are sensitive to nerve root compression in patients with stenosis as a result of age-related lumbar degeneration. Critically, they show that the changes in microstructural integrity along compressed L5 nerve roots are closely related to a number of clinical symptoms associated with the development of chronic pain as well as neurophysiological assessments of motor function. These inherent relationships between nerve root damage and phenotype suggest that the use DTI is a promising method as a way to stratify treatment selection and predict outcomes.

Body temperature, cutaneous heat loss and skin blood flow during epidural anaesthesia for emergency caesarean section.

It is not clear how converting epidural analgesia for labour to epidural anaesthesia for emergency caesarean section affects either cutaneous vasomotor tone or mean body temperature. We hypothesised that topping up a labour epidural blocks active cutaneous vasodilation (cutaneous heat loss and skin blood flow decrease), and that as a result mean body temperature increases. Twenty women in established labour had body temperature, cutaneous heat loss and skin blood flow recorded before and after epidural top-up for emergency caesarean section. Changes over time were analysed with repeated measures ANOVA. Mean (SD) mean body temperature was 36.8 (0.5)°C at epidural top-up and 36.9 (0.6)°C at delivery. Between epidural top-up and delivery, the mean (SD) rate of increase in mean body temperature was 0.5 (0.5) °C.h-1 . Following epidural top-up, chest (p < 0.001) and forearm (p = 0.004) heat loss decreased, but head (p = 0.05), thigh (p = 0.79) and calf (p = 1.00) heat loss did not change. The mean (SD) decrease in heat loss was 15 (19) % (p < 0.001). Neither arm (p = 0.06) nor thigh (p = 0.10) skin blood flow changed following epidural top-up. Despite the lack of change in skin blood flow, the most plausible explanation for the reduction in heat loss and the increase in mean body temperature is blockade of active cutaneous vasodilation. It is possible that a similar mechanism is responsible for the hyperthermia associated with labour epidural analgesia.

Frequency-dependent top-down modulation of temporal summation by anodal transcranial direct-current stimulation of the primary motor cortex in healthy adults.

BACKGROUND: Transcranial direct-current stimulation (tDCS) applied over the primary motor cortex has been shown to be effective in the treatment of a number of chronic pain conditions. However, there is a lack of understanding of the top-down analgesic mechanisms involved. METHOD: In this study, we investigated the effects of tDCS on the facilitation of subjective sensory and pain scores using a transcutaneous electrically evoked measure of temporal summation. In this randomized, blinded, cross-over study healthy subjects received a single stimulus given at 0.9× pain threshold (pTh) over the L5 dermatome on the lateral aspect of the right leg, followed by a train of 5 stimuli given at 0.5, 1, 5 and 20 Hz before and after 20 min of sham or anodal tDCS (2 mA) applied over the primary motor cortex. Ratings of sensation and pain intensity were scored on a visual analogue scale (VAS). RESULTS: Temporal summation leading to pain only occurred at higher frequencies (5 and 20 Hz). Sham or real tDCS had no effect over temporal summation evoked at 5 Hz; however, there was a significant analgesic effect at 20 Hz. Sham or real tDCS had no effect over acute, single stimuli-evoked responses. CONCLUSION: These results indicate that anodal tDCS applied to the primary motor cortex preferentially modulates temporal summation induced by high-frequency electrical stimulation-induced pain. The inhibitory effects of tDCS appear to be dynamic and dependent on the degree of spinal cord excitability and may explain the higher analgesic efficacy in patients with moderate to severe chronic pain symptoms. SIGNIFICANCE: The analgesic effects of tDCS are dependent on spinal cord excitability. This work provides insight into top-down modulation during acute pain and temporal summation. This knowledge may explain why tDCS has a higher analgesic efficacy in chronic pain patients.

Relationships between the integrity and function of lumbar nerve roots as assessed by diffusion tensor imaging and neurophysiology.

PURPOSE: Diffusion tensor imaging (DTI) has shown promise in the measurement of peripheral nerve integrity, although the optimal way to apply the technique for the study of lumbar spinal nerves is unclear. The aims of this study are to use an improved DTI acquisition to investigate lumbar nerve root integrity and correlate this with functional measures using neurophysiology. METHODS: Twenty healthy volunteers underwent 3 T DTI of the L5/S1 area. Regions of interest were applied to L5 and S1 nerve roots, and DTI metrics (fractional anisotropy, mean, axial and radial diffusivity) were derived. Neurophysiological measures were obtained from muscles innervated by L5/S1 nerves; these included the slope of motor-evoked potential input-output curves, F-wave latency, maximal motor response, and central and peripheral motor conduction times. RESULTS: DTI metrics were similar between the left and right sides and between vertebral levels. Conversely, significant differences in DTI measures were seen along the course of the nerves. Regression analyses revealed that DTI metrics of the L5 nerve correlated with neurophysiological measures from the muscle innervated by it. CONCLUSION: The current findings suggest that DTI has the potential to be used for assessing lumbar spinal nerve integrity and that parameters derived from DTI provide quantitative information which reflects their function.

Voluntary activation of trunk extensors appears normal in young adults who have recovered from low back pain.

BACKGROUND: Low back pain (LBP) is associated with alterations in control of trunk movements and changes within central nervous system (CNS). Evidence shows that some of these alterations within the CNS are reversible when the symptoms are relieved, whereas other shows the opposite. Therefore, the purpose of the current study was to investigate whether alterations in voluntary activation (VA) of central neural drive, as assessed using twitch interpolation to measure VA, are present in subjects with a history of low back pain (HLBP), who are free from pain at the time of experiment. METHODS: Twelve adults with HLBP and 12 controls participated. Bilateral electromyographic recordings were obtained from erector spiane muscles at two vertebral levels (T12 and L4) and from rectus abdominis. Participants performed a series of brief isometric back extensions (50-100% maximum voluntary contraction) during which transcranial magnetic stimulation was delivered. The sizes of the evoked (superimposed) twitches were measured using dynamometry and VA was derived. The amplitude of motor evoked potentials (MEPs) and duration of cortical silent period (CSP) in erector spinae muscles were calculated; questionnaires were used to evaluate disability, levels of physical activity, quality of life and pain. RESULTS: The level of VA was not significantly different between HLBP and control groups. Additionally, there were no between-group differences in the time-to-peak amplitudes of the twitches, MEP amplitudes or duration of CSP. CONCLUSIONS: The ability to voluntarily activate back extensor muscles maximally does not appear to be impaired in subjects with a history of LBP during pain-free episodes.

Impaired neural drive in patients with low back pain.

BACKGROUND: Control of trunk movement relies on the integration between central neuronal circuits and peripheral skeletomuscular activities and it can be altered by pain. There is increasing evidence that there are deficits within the central nervous system controlling the trunk muscles in people with low back pain (LBP). However, it is unclear how LBP impacts upon neural drive to back muscles at different levels of voluntary contraction. Therefore, the purpose of this study was to investigate if neural drive is impaired in these patients. METHODS: Seventeen patients with LBP and 11 healthy controls were recruited. Bilateral electromyographic (EMG) recordings were obtained from the erector spinae (ES) muscles at two vertebral levels (T12 and L4). Participants performed a series of brief isometric back extensions (50-100% maximum voluntary contraction - MVC), during which transcranial magnetic stimulation was delivered. The size of the evoked (superimposed) twitch was measured using dynamometry. RESULTS: The size of the superimposed twitch decreased linearly with increasing contraction strength in the controls; however, this linear relationship was not observed in the patients. Additionally, patients had larger superimposed twitches and longer time-to-peak amplitudes during MVCs than those observed in controls. Furthermore, patients had lower MVC and root-mean-square EMG activity of ES muscles during MVCs. CONCLUSIONS: A decline of central neural drive to the back muscles at high level of voluntary contraction was observed in patients with LBP. These results suggest that it might be pertinent to include neuromuscular facilitation programmes and therapeutic exercise utilizing high voluntary contractions for patients with LBP.

Effect of dual tasking on postural responses to rapid lower limb movement while seated on an exercise ball.

Postural adjustments are used by the central nervous system to pre-empt and correct perturbations in balance during voluntary body movements. Alteration in these responses is associated with a number of neuromuscular/musculoskeletal conditions. Attention has been identified as important in this system; performing a concurrent cognitive task has been suggested to reduce the efficacy of this postural control. The aim of this study was to examine the effect of concurrent cognitive tasking on anticipatory postural adjustments while sitting on an exercise ball with a view to help inform future rehabilitation programmes. Bilateral EMG activity was recorded from the external and internal obliques, rectus abdominis, erector spinae and the right rectus femoris of 20 healthy subjects (9 males) with mean (SD) age of 21.88 (0.86) years (range 21-24 years). A rapid hip flexion protocol was carried out under three conditions: no concurrent task, counting out loud up from one and completing a serial sevens task. The addition of the cognitive task delayed and reduced the EMG in the prime mover muscle but had little impact on the responses of the trunk muscles within the time frame of the anticipatory responses; suggestive of a decoupling of voluntary and postural control mechanisms. The results of this study suggest that perhaps the clinical effects of dual task may not be largely due to changes in anticipatory postural adjustments. However, it would be important to compare these results to those seen in older and functionally impaired individuals as this would be more representative of the typical population undertaking such rehabilitation programmes.

The effect of an exercise ball on trunk muscle responses to rapid limb movement.

The use of exercise balls as an aid to facilitate improvements in posture in patients with trunk weakness is widely advocated. However, mechanisms underlying any effect on postural mechanisms have received little attention. This study compared the increases in trunk EMG activity in response to limb movement when seated on an exercise ball or on a chair in 16 healthy, moderately active subjects. At the sound of an auditory cue, the subjects carried out either hip flexion or arm flexion (unilateral or bilateral), as fast as possible, whilst sitting on an exercise ball or a standard chair. The amplitude of EMG activity was recorded from selected trunk muscles (erector spinae, external obliques, internal obliques and rectus abdominis) and either an upper limb muscle (deltoid) or a lower limb muscle (rectus femoris). There were minimal differences in amplitudes of EMG activity in any of the trunk muscles between the conditions (ball or chair) following the upper limb movements. These results suggest that there is no benefit in simple arm flexion movements whilst seated on the exercise ball in comparison to a chair. The onset and amplitude of the rectus abdominis (RA) and external obliques (EO) were significantly different between conditions in the hip flexion protocol. However, they do suggest significant benefit in decreasing RA and EO muscle activity onsets and increasing amplitude in the hip flexion condition. These results may have implications for rehabilitation of those with trunk muscle deficits such as stroke.

Interaction between vestibulo-spinal and corticospinal systems: a combined caloric and transcranial magnetic stimulation study.

We investigated the interaction between vestibular and corticospinal stimuli in 8 healthy volunteers. Vestibular stimulation was induced with unilateral ear caloric irrigation (30°C) with subjects supine. Single transcranial magnetic stimulation (TMS) pulses were delivered (double-cone coil, intensities 60-75% maximal output) every 10-20 s during vestibular activation and during baseline. Bilateral surface electromyography (EMG) from splenius capitis, sternocleidomastoid (SCM), obliquus externus abdominis, vastus lateralis, biceps femoris (BF), tibialis anterior and peroneus longus was obtained. During whole-body maximal rotatory voluntary isometric contraction (MRVC), only SCM and BF displayed EMG activation/inhibition patterns indicating axial rotatory action. TMS-induced motor evoked potentials (MEPs) after caloric irrigation revealed that only SCM showed consistent vestibular-mediated excitation/inhibition responses, i.e. an increase in MEP area contralateral to the irrigation and a decrease in MEP area ipsilaterally (+12.7 and -6.3% of the MRVC, respectively). A putative head turn induced by this SCM activity pattern would be in the same direction of the slow-phase eye movement. EMG in the 100 ms preceding TMS showed muscle tone values of approximately 10% of MRVC. After caloric irrigation, these values increased by ca. 2% for all muscles bilaterally and hence cannot explain the direction-specific SCM MEP changes. Thus, SCM MEPs show caloric-induced amplitude modulation indicating that SCM is under both horizontal semicircular canal and corticospinal control. This vestibular modulation of corticospinal SCM control likely occurs at cortical levels. The direction of the MEP modulation indicates a directional coupling between vestibularly induced head and eye movements.

Establishment of a protocol to test fatigue of the trunk muscles.

BACKGROUND: Muscle fatigue has high relevance in human performance yet little research has evaluated how it should be assessed. OBJECTIVE: To perform a pilot study to identify suitable methods of generating and assessing fatigue of the trunk flexor and extensor muscles. METHODS: Sixteen university rugby players (mean (SEM) age 21.9 (0.2) years) were recruited and subjected to four protocols (A, B, C, D), separated by a week to allow recovery, with peak torque being recorded during each test: A, isokinetic measurements before and after fatigue, with a 10 repetition isokinetic fatigue period; B, isokinetic measurements before and after fatigue with a 45 second isometric fatigue period; C, isometric measurements before and after fatigue with a 10 repetition isokinetic fatigue period; D, isometric measurements before and after fatigue with a 45 second isometric fatigue period. All were conducted during flexion and extension of the trunk on the Cybex Norm Isokinetic Dynamometer trunk flexion-extension unit. RESULTS: All subjects completed all four protocols. Fatigue induction appeared more effective in flexion than extension. Significant differences in mean peak torque before and after fatigue were seen in protocols A, B, and D in flexion and only in protocol D for extension. In flexion, protocol D produced the greatest fatigue, peak torque being 16.2% less after than before fatigue, suggesting greatest sensitivity. CONCLUSIONS: Protocol D, which incorporates isometric testing and fatigue protocols, appears to be able to produce fatigue most effectively, and therefore may provide the most valid assessment of fatigue in the trunk flexor and extensor muscles.

Motor neurone excitability in back muscles assessed using mechanically evoked reflexes in spinal cord injured patients.

OBJECTIVE: The clinical and functional assessment of back muscles in human spinal cord injury (SCI) has received little attention. The aim of this study was to develop a method to assess the level of a thoracic spinal cord lesion based on the reflex activation of back muscles. METHODS: In 11 control subjects and in 12 subjects with clinically complete thoracic SCI (T2-T12), either a spinous process or an erector spinae muscle was prodded to elicit short latency reflexes recorded electromyographically at the spinal level of stimulation. An electromagnetic servo, attached to a blunt probe, applied stimuli at a frequency of 1 Hz and amplitude of 3 mm. Two trials of 50 mechanical prods were conducted at each site. RESULTS: Reflexes were evoked in control subjects in 82% of trials when the spinous process was prodded, and in 80% of trials when the muscle was prodded. In contrast, reflexes in SCI subjects could be elicited in 90-100% of trials two segments either above or below the lesion. Reflex responses in control subjects had a mean (SEM) latency of 5.72 (0.53) ms when the spinous process was prodded, and 5.42 (0.42) ms when the muscle was prodded. In the SCI subjects, responses had slightly (but insignificantly) longer latencies both above and below the lesion to either stimulus. The amplitude of reflex responses, expressed as a percentage of the background EMG, was on average 2-3 times larger at the three vertebral levels spanning the lesion in SCI subjects than at sites above or below the lesion or at any level in control subjects. CONCLUSION: We propose that the size of these mechanically evoked reflexes may be useful in determining the level of thoracic SCI. Furthermore, the reflexes might provide a valuable tool with which to monitor recovery after an intervention to repair or improve function of a damaged spinal cord.

The effect of an energy drink containing glucose and caffeine on human corticospinal excitability.

Glucose- and caffeine-containing energy drinks are said to influence the cognitive and cellular function within the brain. In this study, we have used the size of motor-evoked potentials (MEPs) produced in response to transcranial magnetic stimulation (TMS) of the motor cortex as an index of corticospinal excitability after ingestion of Lucozade and control drinks of glucose-containing or caffeine-containing carbonated water or carbonated water alone. With local ethical approval and informed consent, 10 healthy volunteers took part; surface electromyographic (EMG) recordings were taken from the thenar muscles of the dominant hand. In each assessment, 15 TMS stimuli were delivered over the motor cortex at an intensity of 1.1 T. Six subjects ingested a 380-ml bottle of carbonated Lucozade drink containing 68 g of glucose and 46 mg caffeine. Four subjects took part in three control trials drinking: (A) carbonated water with caffeine, (B) carbonated water with glucose and (C) carbonated water alone. Assessments were made before and at 30-min intervals after each drink. Mean fasting blood glucose concentrations and mean areas of MEPs rose after the Lucozade, remaining elevated for 90 min. Similar rises in MEP areas were seen in trials after drinking carbonated water with caffeine or with glucose, but not after drinking carbonated water alone. No change was seen in the M-wave evoked by electrical stimulation of the ulnar nerve. We conclude that Lucozade can affect the size of MEPs to activation of the motor cortex with fixed-intensity TMS. The underlying mechanism is likely to relate to the combined effects of caffeine and glucose on the brain.

Specificity and functional impact of post-exercise depression of cortically evoked motor potentials in man.

Magnetic stimulation of the motor cortex with electromyographic recordings from exercising muscles has shown corticospinal excitability to be depressed following exercise. We now investigate whether this depression spreads to non-exercising muscles and its influence on performance. Healthy volunteers made unilateral biceps curls to exhaustion and, in another later session, for 25% of the time to exhaustion. Bilateral motor-evoked potentials (MEPs) in biceps brachii and first dorsal interosseus muscles were measured at 2-min intervals before and after exercise. In another experiment, subjects performed exhaustive curls and, in addition to MEP areas, force production in biceps, hand-grip force, simple reaction times and movement times were measured bilaterally. MEPs were depressed after exhaustive exercise in the exercising biceps for over 60 min; depression was also observed 10-15 min after exercise in the non-exercising biceps but not in the first dorsal interosseus of either hand. The shorter exercise period produced depression of MEPs only in the exercising muscle. After exhaustive exercise maximum voluntary contraction fell in the exercising biceps and this correlated with MEP areas. No reduction in force was seen in the non-exercising biceps but hand-grip force fell slightly in both arms. There was no change in reaction times or movement times. Depression of MEPs can occur in non-exercising homonymous muscles but not in heteronymous muscles and only when exercise levels are high. There was no measurable functional deficit in the non-exercising limb, so we conclude that the reduced corticospinal excitability observed in this limb has little or no consequence on the performance parameters measured.

Ketamine-induced general anesthesia is compatible with gonadotropin-releasing hormone pulse generator activity in gonadectomized rats: prospects for detailed electrophysiological studies in vivo.

Previous studies on the mediobasal hypothalamus (MBH) of rats, rhesus monkeys and goats have detected episodic increases in multiunit activity (MUA volleys) which immediately precede a pulse of luteinizing hormone (LH). These volleys are considered to reflect the activity of the gonadotropin-releasing hormone (GnRH) pulse generator. Our understanding of this system would be greatly enhanced if it were possible to study the electrophysiological aspects of this system at the single cell level; such an approach requires anesthesia of the animals (as in the classic studies on the oxytocin and vasopressin systems). Although it is widely held that anesthetic agents disrupt the processes regulating LH release, little is known about their specific effects on the dynamics of this system. Using on-line electrophysiological techniques in addition to subsequent radioimmunoassay for LH, we have found that anesthesia by ketamine is compatible with the continued production of MUA volleys and LH pulses in gonadectomized rats. In contrast to the hypothermia induced by the LH pulse-suppressing anesthetic sodium pentobarbitone, a small rise in core temperature occurs following ketamine. The present findings offer the prospect of detailed electrophysiological analysis of GnRH pulse generator activity in rats maintained under general anesthesia.

Estrogen receptor immunoreactivity is present in the majority of central histaminergic neurons: evidence for a new neuroendocrine pathway associated with luteinizing hormone-releasing hormone-synthesizing neurons in rats and humans.

The central regulation of the preovulatory LH surge requires a complex sequence of interactions between neuronal systems that impinge on LH-releasing hormone (LHRH)-synthesizing neurons. The reported absence of estrogen receptors (ERs) in LHRH neurons indicates that estrogen-receptive neurons that are afferent to LHRH neurons are involved in mediating the effects of this steroid. We now present evidence indicating that central histaminergic neurons, exclusively located in the tuberomammillary complex of the caudal diencephalon, serve as an important relay in this system. Evaluation of this system revealed that 76% of histamine-synthesising neurons display ERalpha-immunoreactivity in their nucleus; furthermore histaminergic axons exhibit axo-dendritic and axo-somatic appositions onto LHRH neurons in both the rodent and the human brain. Our in vivo studies show that the intracerebroventricular administration of the histamine-1 (H1) receptor antagonist, mepyramine, but not the H2 receptor antagonist, ranitidine, can block the LH surge in ovariectomized estrogen-treated rats. These data are consistent with the hypothesis that the positive feedback effect of estrogen in the induction of the LH surge involves estrogen-receptive histamine-containing neurons in the tuberomammillary nucleus that relay the steroid signal to LHRH neurons via H1 receptors.

Adrenomedullectomy prevents the suppression of pulsatile luteinising hormone release during fasting in female rats.

Fasting inhibits the pulsatile secretion of luteinising hormone (LH) in female rats, an effect which is potentiated by the presence of oestradiol (E2). We have previously described various pharmacological or surgical treatments that can rapidly restore the pulses in a fasting animal. Nevertheless, the central and peripheral mechanisms that mediate this suppression of the pulses remain unclear. We have recently shown that adrenomedullectomy prevents the suppression of LH pulses by insulin-induced hypoglycaemia, a state which activates the sympathoadrenal axis. The present study was undertaken to establish whether this axis might contribute to the loss of the pulses that occurs in ovariectomised E2-treated rats that have been fasted for 48 h. Following sham adrenomedullectomy LH pulses were observed in animals fed ad libitum; after 48 h of fasting the animals that had received this sham procedure showed a significant suppression of LH levels and LH pulse frequency. In contrast, adrenomedullectomy prevented the inhibition of the pulses by 48 h of fasting; it had no effect on the pulses in the absence of fasting. These results suggest that adrenomedullary activity plays a significant role in the fasting-induced suppression of LH pulses in rats.