Paul H. Strutton

Corticospinal excitability in patients with chronic low back pain.

Objective: This study was designed to investigate corticospinal excitability of lumbar muscles using transcranial magnetic stimulation (TMS) in patients with chronic low back pain and correlate this with self-rated measures of disability and pain. Methods: Twenty-four patients with chronic low back pain and 11 healthy control subjects were used in this study. TMS was delivered through an angled double-cone coil, with its cross-over on the vertex and a posterior-to-anterior current flow in the brain. Electromyographic (EMG) recordings were made from erector spinae (ES) muscles at the fourth lumbar level. Motor cortical excitability was assessed using motor threshold (MTh) for motor evoked potentials (MEPs) and threshold for silent period (SP) during facilitation of the back muscles. Latency, duration, and area of MEPs and SPs were also measured. Results: The latency, duration, and size of MEPs and SPs did not differ between the left and right ES muscles in either the patients or the control subjects and also did not differ between the patients and the control subjects. However, there was a significantly higher MTh and threshold for the SP in the patients as compared with the control subjects; the full significance of this requires further investigation. Interestingly, there was a positive correlation between the self-rated measure of disability (the Oswestry Disability Index score) and both the MTh and the threshold for the SP in the patients. There was also a positive correlation between the self-rated index of back pain and the threshold for the SP in the patients. This finding of an association between clinical and neurophysiologic measures reinforces the need for further research to establish the clinical relevance of these rises in MTh and SP threshold. Conclusions: In summary, this study has revealed that corticospinal excitability, driving ES muscles close to the site of pain, is lowered in patients with chronic low back pain.

Hypoglycaemia-Induced Inhibition of Pulsatile Luteinizing Hormone Secretion in Female Rats: Role of Oestradiol, Endogenous Opioids and the Adrenal Medulla

Oestradiol (E2) has been shown to exacerbate the inhibitory effect of hypoglycaemic stress on gonadotrophin‐releasing hormone pulse generator (GnRH) activity in primates. The mechanism by which this is mediated is not yet known. We therefore aimed to establish whether there is a sensitizing influence of E2 on the suppression of LH pulsatility in response to hypoglycaemia in the female rat, thus providing a more amenable model in which to study this phenomenon. In ovariectomized Wistar rats with E2 replacement, insulin‐induced hypoglycaemia (0.5 U/kg iv) resulted in an interruption of pulsatile LH secretion. Induction of the same degree of hypoglycaemia in ovariectomized rats without E2 replacement was without effect on LH pulsatility. Naloxone administration prevented the hypoglycaemia‐induced inhibition of LH pulses. Because hypoglycaemia is a potent activator of the sympathetic nervous system, we also tested the hypothesis that the adrenal medulla is involved in this suppression of LH pulses in the rat. Adrenomedullectomy completely prevented this inhibitory response to hypoglycaemic stress. These data are consistent with the hypothesis that E2 sensitizes the GnRH pulse generator to the inhibitory influences of hypoglycaemic stress in the rat. Furthermore, a clear role for both endogenous opioid peptides and the adrenal medulla in the stress‐induced suppression of LH pulsatility is identified.

Review of physiological motor outcome measures in spinal cord injury using transcranial magnetic stimulation and spinal reflexes

This article reviews methods that have been developed as part of a clinical initiative on improving outcome measures for motor function assessment in subjects with spinal cord injury (SCI). Physiological motor outcome measures originally developed for limbs-transcranial magnetic stimulation (TMS) of the motor cortex to elicit motor-evoked potentials (MEPs) and mechanical stimulation to elicit spinal reflexes-have been extended to muscles of the trunk. The impetus for this development is the lack of a motor component in the American Spinal Injury Association clinical assessment for the thoracic myotomes. The application of TMS to the assessment of limb muscles is reviewed, followed by consideration of its application to the assessment of paravertebral and intercostal muscles. Spinal reflex testing of paravertebral muscles is also described. The principal markers for the thoracic SCI motor level that have emerged from this clinical initiative are (1) the threshold of MEPs in paravertebral muscles in response to TMS of the motor cortex, (2) the facilitation pattern and latency of MEPs in intercostal muscles during voluntary expiratory effort, and (3) the absence of long-latency reflex responses and the exaggeration of short-latency reflex responses in paravertebral muscles.

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 ERα-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,...

Estimation of cortical silent period following transcranial magnetic stimulation using a computerised cumulative sum method.

The cortical silent period (CSP) following transcranial magnetic stimulation (TMS) of the motor cortex can be used to measure intra-cortical inhibition and changes in a number of important pathologies affecting the central nervous system. The main drawback of this technique has been the difficulty in accurately identifying the onset and offset of the cortical silent period leading to inter-observer variability. We developed an automated method based on the cumulative sum (Cusum) technique to improve the determination of the duration and area of the cortical silent period. This was compared with experienced raters and two other automated methods. We showed that the automated Cusum method reliably correlated with the experienced raters for both duration and area of CSP. Compared with the automated methods, the Cusum also showed the strongest correlation with the experienced raters. Our results show the Cusum method to be a simple, graphical and powerful method of detecting low-intensity CSP that can be easily automated using standard software.

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.

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.

Fatigue-induced change in corticospinal drive to back muscles in elite rowers

This study examined post‐exercise changes in corticospinal excitability in five ‘elite’ rowers and six non‐rowers. Transcranial magnetic stimulation (TMS) was delivered to the motor cortex and bilateral electromyographic (EMG) recordings were made from erector spinae (ES) muscles at L3/L4 spinal level and from the first dorsal interosseous (FDI) muscle of the dominant hand. Each subject completed two exercise protocols on a rowing ergometer: a light exercise protocol at a sub‐maximal output for 10 min and an intense exercise protocol at maximum output for 1 min. A trial of ten magnetic stimuli was delivered before each of the protocols and, on finishing exercise, further trials of ten stimuli were delivered every 2 min for a 16 min period. Amplitudes of motor‐evoked potentials (MEPs) in each of the three test muscles were measured before exercise and during the recovery period after exercise. The non‐rowers showed a brief facilitation of MEPs in ES 2 min after light and intense exercise that was only present in the elite rowers after intense exercise. In the period 4‐16 min after light exercise, the mean (± S.E.M.) MEP amplitude (relative to pre‐exercise levels) was less depressed in the elite rowers (79.4 ± 2.1%) than in the non‐rowers (60.9 ± 2.5%) in the left ES but not significantly so in the right ES. MEP amplitudes in FDI were significantly larger in the elite rowers, averaging 119.0 ± 3.1% pre‐exercise levels, compared with 101.2 ± 5.8% in the non‐rowers. Pre‐exercise MEP latencies were no different in the two groups. After light exercise MEP latencies became longer in the elite rowers (left ES, 16.1 ± 0.5 ms; right ES, 16.1 ± 0.4 ms; dominant FDI, 23.4 ± 0.2 ms) than in the non‐rowers (left ES, 15.0 ± 0.3 ms; right ES, 15.2 ± 0.3 ms; dominant FDI, 21.5 ± 0.2 ms). There were no differences in MEP depression or latency between elite rowers and non‐rowers after intense exercise. We conclude that the smaller degree of MEP depression in the elite rowers after light exercise reflects less central fatigue within corticospinal control pathways than that seen in the non‐rowers. The longer latency of MEPs seen in the elite rowers may reflect recruitment of more slower‐conducting fatigue‐resistant motor units compared with the non‐rowers. These differences may be because the energy requirements for the non‐rowers during light exercise are closer to their maximum capacity, leading to more fatigue. This notion is supported by the lack of any difference between groups following intense exercise when both groups were working at their own maximum.

Stability of corticospinal excitability and grip force in intrinsic hand muscles in man over a 24-h period

The maximum voluntary muscle force can vary throughout the day; typically being low in the morning and high in the evening. The nature of this possible variation has been investigated with respect to corticospinal excitability. Six healthy subjects were studied. Maximum voluntary contraction (MVC) in the thenar muscles was measured. In addition, we monitored several indices of corticospinal excitability using electromyographic (EMG) recording and transcranial magnetic stimulation (TMS) of the motor cortex. Motor evoked potentials (MEPs) were recorded while relaxed and at 10% MVC when the silent period was assessed as an index of corticospinal inhibition. Readings were taken every 3 h for 24 h. MVC of the thenar muscles did not change significantly over the 24 h. The mean areas, latencies and durations of MEPs did not show significant changes over the 24-h test period with the muscle relaxed or contracted; however, MEP area did vary between sessions at all stimulus intensities suggesting non-time-of-day-dependent changes in corticospinal excitability. Furthermore, the extent and duration of the silent period seen after the MEP in the contracted muscle did not change significantly over the 24 h of the experiment at any stimulus intensity. These results provide evidence that the MVC force of the thenar muscles and their responses to TMS are stable throughout the course of the day and suggest that, in hand muscles, corticospinal excitability may not be subject to circadian variation.

Impaired neural drive in patients with low back pain

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.