A Systematic Review of the Diagnostic Criteria Used to Select Participants in Randomised Controlled Trials of Interventions Used to Treat Cervicogenic Headache.

OBJECTIVE: The aim of this study was to determine the diagnostic criteria used in randomized controlled trials to define trial participants as having cervicogenic headache (CeH). BACKGROUND: While animal and human studies suggest a biological basis for "cervicogenic" headaches the diagnostic criteria necessary to evidence CeH are debated. METHODS: A systematic review was undertaken guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. An electronic search of MEDLINE, Cochrane, CINHAL, Pedro, AMED, and EMBASE online databases of randomized controlled trials published between January 1983 and October 2018 found 39 randomized controlled trials which met the study inclusion criteria. RESULTS: Two independent reviewers found most trials cited 1 (31/39; 79.5%) or more (3/39; 7.6%) references to define the criteria used to identify CeH in their study participants. In spite of updated publications concerning the characteristics and definition of CeH, many (27/39; 69.2%) used diagnostic criteria published between 5 and 24 years prior to the randomized controlled trial. The most commonly cited diagnostic criteria included unilateral headache (18/39; 46.2%), cervical movement or sustained posture that either provoked (18/39; 46.2%) or precipitated (17/39; 43.6%) the headache. Fifteen trials did not exclude participants with signs or symptoms of other forms of headache. Although anesthetic blockade of cervical tissue or nerves is considered necessary for a "definitive" diagnosis, only 7.6% (3/39) of trials used anesthetic blockade at recruitment. CONCLUSIONS: This systematic review evidences the heterogeneity in the clinical characteristics used to diagnose CeH in participants recruited in randomized controlled trials. It raises a significant concern about the usefulness of currently available randomized controlled trials to determine the clinical merits of the treatment and management of people with CeHs. Our systematic review suggests that most randomized controlled trials published to date have investigated headaches with a clinical presentation involving the neck that maybe better defined as "possible," "probable," or "definitive" CeH depending on how well the diagnostic criteria used align with the most recent edition (3rd) of the International Classification of Headache Disorders.

Neck movement but not neck position modulates skin sympathetic nerve activity supplying the lower limbs of humans.

We previously showed that dynamic, but not static, neck displacement modulates muscle sympathetic nerve activity (MSNA) to lower limbs of humans. However, it is not known whether dynamic neck displacement modulates skin sympathetic nerve activity (SSNA). Tungsten microelectrodes inserted into the common peroneal nerve were used to record SSNA in 5 female and 4 male subjects lying supine on a table that fixed their head in space but allowed trapezoidal ramp (8.1 ± 1.2°/s) and hold (17.5° for 53 s) or sinusoidal (35° peak to peak at 0.33-0.46 Hz) horizontal displacement of the body about the head. SSNA recordings were made before, during, and after trapezoidal and sinusoidal displacements of the body. Spike frequency analysis of trapezoidal displacements and cross-correlation analysis during sinusoidal displacements revealed that SSNA was not changed by trapezoid body-only displacement but was cyclically modulated during sinusoidal angular displacements (median, 95% CI: 27.9%, 19.6-48.0%). The magnitude of this modulation was not statistically ( P > 0.05) different from that of cardiac and respiratory modulation at rest (47.1%, 18.7-56.3% and 48.6%, 28.4-59.3%, respectively) or during sinusoidal displacement (10.3%, 6.2-32.1% and 26.9%, 13.6-43.3%, respectively). Respiratory frequency was entrained above its resting rate (0.26 Hz, 0.2-0.29 Hz) during sinusoidal neck displacement; there was no significant difference ( P > 0.05) between respiratory frequency (0.38 Hz, 0.25-0.49 Hz) and sinusoidal displacement frequency (0.39 Hz, 0.35-0.42 Hz). This study provides evidence that SSNA is modulated during neck movement, raising the possibility that neck mechanoreceptors may contribute to the cutaneous vasoconstriction and sweat release associated with motion sickness. NEW & NOTEWORTHY This study demonstrates that dynamic, but not static, stretching of the neck modulates skin sympathetic nerve activity in the lower limbs.

Contrasting alterations to synaptic and intrinsic properties in upper-cervical superficial dorsal horn neurons following acute neck muscle inflammation.

BACKGROUND: Acute and chronic pain in axial structures, like the back and neck, are difficult to treat, and have incidence as high as 15%. Surprisingly, most preclinical work on pain mechanisms focuses on cutaneous structures in the limbs and animal models of axial pain are not widely available. Accordingly, we developed a mouse model of acute cervical muscle inflammation and assessed the functional properties of superficial dorsal horn (SDH) neurons. RESULTS: Male C57/Bl6 mice (P24-P40) were deeply anaesthetised (urethane 2.2 g/kg i.p) and the rectus capitis major muscle (RCM) injected with 40 µl of 2% carrageenan. Sham animals received vehicle injection and controls remained anaesthetised for 2 hrs. Mice in each group were sacrificed at 2 hrs for analysis. c-Fos staining was used to determine the location of activated neurons. c-Fos labelling in carrageenan-injected mice was concentrated within ipsilateral (87% and 63% of labelled neurons in C1 and C2 segments, respectively) and contralateral laminae I - II with some expression in lateral lamina V. c-Fos expression remained below detectable levels in control and sham animals. In additional experiments, whole cell recordings were obtained from visualised SDH neurons in transverse slices in the ipsilateral C1 and C2 spinal segments. Resting membrane potential and input resistance were not altered. Mean spontaneous EPSC amplitude was reduced by ~20% in neurons from carrageenan-injected mice versus control and sham animals (20.63 ± 1.05 vs. 24.64 ± 0.91 and 25.87 ± 1.32 pA, respectively). The amplitude (238 ± 33 vs. 494 ± 96 and 593 ± 167 pA) and inactivation time constant (12.9 ± 1.5 vs. 22.1 ± 3.6 and 15.3 ± 1.4 ms) of the rapid A type potassium current (IAr), the dominant subthreshold current in SDH neurons, were reduced in carrageenan-injected mice. CONCLUSIONS: Excitatory synaptic drive onto, and important intrinsic properties (i.e., IAr) within SDH neurons are reduced two hours after acute muscle inflammation. We propose this time point represents an important transition period between peripheral and central sensitisation with reduced excitatory drive providing an initial neuroprotective mechanism during the early stages of the progression towards central sensitisation.

What are the temporal and physical characteristics of locally applied vibration that modulate balance in older adults? - A systematic review of the literature.

BACKGROUND: Compromised balance is known to contribute to falls, which are associated with increased morbidity and mortality for older adults. Evidence suggests that the application of local vibration to the lower limbs of older adults has the potential to modulate balance. RESEARCH QUESTION: To identify the temporal and mechanical parameters of vibration applied locally to the lower limbs of older adults that modulate measures of balance, and to define the short- and long-term effects of vibration on balance in this population. METHODS: The PRISMA 2020 guidelines were used to conduct a systematic search including the PUBMED, EMBASE, and Scopus databases to identify peer-reviewed literature where vibration was applied to the lower limbs of older adults to modulate balance. Data was extracted using a study-specific data extraction form and risk of bias assessed. Where possible, effect sizes were calculated. RESULTS: Of 7777 records screened, ten randomised controlled trials and 43 prospective laboratory-based studies met the inclusion criteria. Vibration frequencies ranged from 1 to 272 Hz, most studies (n=41) used ≤100 Hz. Amplitude ranged from 0.2 to 3.0 mm, most studies (n=28) used ≤1 mm. Effects of short-term vibration (applied for seconds to hours) were measured during and/or immediately after application. Short-term suprathreshold perceived muscle/tendon vibration had a 'large' destabilising effect size on balance in healthy older adults, but little or no effect on older fallers. Short-term subthreshold vibration to the soles of the feet had a 'small' stabilising effect size. Suprathreshold muscle, tendon or sole vibration applied for 10-30 min over days to weeks improved balance measures, but most (8 of 10) had increased risk of bias. SIGNIFICANCE: The heterogeneity of methodology, populations, and vibration and balance parameters precluded conclusions about the relative effects of lower limb vibration in older adults. However, these results suggest that the application of local vibration to the lower limbs of older adults can modulate balance in the short- and long-term.

What are the clinical criteria justifying spinal manipulative therapy for neck pain?- a systematic review of randomized controlled trials.

OBJECTIVE: Manipulation and mobilization are used to treat neck pain. However, little is known about the diagnostic criteria used to determine the need for manipulation in cases of neck pain. The primary aim of this study was to determine what diagnostic criteria are used to identify which neck pain sufferers should receive spinal manipulation or mobilization. DESIGN: We systematically reviewed randomized controlled trials (RCT) involving mobilization or manipulation for neck pain. A data extraction pro forma was developed and trialled before two independent assessors extracted data sets from each RCT. A descriptive analysis was undertaken. RESULTS: Thirty RCTs met the inclusion criteria. Acute and chronic "Mechanical" neck pain was the most common (43%) diagnosis at recruitment to the RCTs but some (10%) included patients with cervicogenic headache. Clinical criteria were used to determine the need for neck manipulation in over half (63%) of the RCTs. This usually involved exclusion of serious conditions, manual examination for tenderness on palpation, and/or altered vertebral motion in the neck or upper thoracic region which are known to lack validity. The remainder of the RCTs did not report a diagnostic strategy. All RCTs lacked detail descriptions of diagnostic criteria or interventions used. CONCLUSIONS: This systematic review highlights the absence of reliable and valid diagnostic protocols to determine the need for spinal manipulation in persons presenting with non-serious, idiopathic, or whiplash-associated (grade II) neck pain. Guidelines requiring the reporting of valid diagnostic criteria are needed to improve the quality of RCTs concerning manual therapy.

Cerebrospinal fluid pressure response to upper cervical vertebral motion and displacement in the anesthetized rat.

OBJECTIVE: This study examined whether aligned or off-axis (subluxated) static and dynamic vertebral displacement within normal physiological ranges modulated cerebrospinal fluid pressure (CSF) as is considered to occur by some chiropractic theories. METHODS: Cerebrospinal fluid pressure pressure was measured via a subarachnoid catheter implanted at the lumbar level in 12 anesthetized adult male Wistar rats. A computer-driven manipulator was used to impose 3 motion patterns on the C2 vertebra: (i) dynamic oscillatory displacement (24 degrees peak-to-peak 1.0 and 2.0 Hz), (ii) static rotary (ramp 20 degrees at 10 degrees per second and hold for 4 minutes) displacement about both the normal and an offset axis of rotation, and (iii) a spinal manipulative thrust displacement (200 degrees per second; 12 degrees peak-to-peak). RESULTS: The CSF pressure at rest for all rats ranged from 4.5 to 9.1 mm Hg, with a mean (+/- SD) of 6.3 +/- 1.4 mm Hg. Of the imposed movements, only an offset ramp and hold displacement resulted in a significant (P < .05) difference between the CSF pressure before (6.1 +/- 0.7 mm Hg) and during the imposed movement (6.6 +/- 0.7 mm Hg). None of the interventions were associated with significant changes in the powers of the principal peaks of the CSF pressure power spectrum. CONCLUSIONS: The results of this study suggest that static or dynamic displacement of an upper cervical vertebra within the limits of tissue integrity do not induce physiologically important changes in absolute CSF pressure or pressure dynamics in anesthetized rats.

Cerebrospinal fluid pressure in the anesthetized rat.

OBJECTIVE: The primary aims of this study were to determine the major frequencies and powers of oscillations in cerebrospinal fluid (CSF) pressure in the anesthetized rat, and determine whether the CSF pressure oscillations correlated with the major oscillation frequencies in the cardiovascular and respiratory systems as proposed by some chiropractic theories. METHODS: The cardiac and ventilatory cycles, and CSF pressure were simultaneously recorded during spontaneous and positive-pressure mechanical ventilation in the anesthetized rat. Power spectra were generated from the raw data to identify the major oscillation frequencies in cardiorespiratory and CSF data sets. Entrainment of CSF pressure with ventilation was tested by mechanically pacing the ventilation over a range of frequencies. RESULTS: The most powerful oscillation in CSF pressure was coincident with ventilatory chest movement during both spontaneous and mechanically paced ventilation. In 22 of 26 trials, there was also a very weak oscillation in CSF pressure that was entrained to heart rate. In addition, in 21 of 26 trials, it was possible to identify a low-frequency oscillation (<0.25 Hz) in CSF pressure that was coincident with a low-frequency oscillation in the power spectrum of the cardiac cycle. CONCLUSIONS: This study suggests oscillations in CSF pressure in the anesthetized rat are entrained to and driven by ventilation. The arterial pulse pressure makes little contribution to oscillations in CSF pressure in the immobile, anesthetized rat. This study provides normative, quantitative data on which to develop studies concerning the effects of vertebral movements and spinal posture on CSF dynamics.

Design, rationale and feasibility of a multidimensional experimental protocol to study early life stress.

There is a rapidly accumulating body of evidence regarding the influential role of early life stress (ELS) upon medical and psychiatric conditions. While self-report instruments, with their intrinsic limitations of recall, remain the primary means of detecting ELS in humans, biological measures are generally limited to a single biological system. This paper describes the design, rationale and feasibility of a study to simultaneously measure neuroendocrine, immune and autonomic nervous system (ANS) responses to psychological and physiological stressors in relation to ELS. Five healthy university students were recruited by advertisement. Exclusion criteria included chronic medical conditions, psychotic disorders, needle phobia, inability to tolerate pain, and those using anti-inflammatory medications. They were clinically interviewed and physiological recordings made over a two-hour period pre, during and post two acute stressors: the cold pressor test and recalling a distressing memory. The Childhood Trauma Questionnaire and the Parental Bonding Index were utilised to measure ELS. Other psychological measures of mood and personality were also administered. Measurements of heart rate, blood pressure, respiratory rate, skin conductance, skin blood flow and temporal plasma samples were successfully obtained before, during and after acute stress. Participants reported the extensive psychological and multisystem physiological data collection and stress provocations were tolerable. Most (4/5) participants indicated a willingness to return to repeat the protocol, indicating acceptability. Our protocol is viable and safe in young physically healthy adults and allows us to assess simultaneously neuroendocrine, immune and autonomic nervous system responses to stressors in persons assessed for ELS.

Spinal manipulation and spinal mobilization influence different axial sensory beds.

Manipulation and mobilization are two forms of manual therapy commonly employed in the management of musculoskeletal disorders. Spinal manipulation and mobilization are often distinguished from one another by reference to certain biomechanical parameters such as peak force, duration and magnitude of translation. However, as of yet, there is relatively little research which distinguishes between them in terms of neurological mechanisms or clinical effectiveness. Theories concerning the mechanisms underlying the therapeutic effects of manipulation and mobilization commonly make reference to mechanical events such as the release of entrapped tissue or the disruption of intra-articular adhesions. Relatively less attention is given to neural effects. In this paper, we hypothesize that, at least in part, spinal manipulation preferentially influences a sensory bed which, in terms of anatomical location and function, is different from the sensory bed influenced by spinal mobilization techniques. More specifically, we hypothesize that manipulation may particularly stimulate receptors within deep intervertebral muscles, while mobilization techniques most likely affect more superficial axial muscles. In part, our rationale for this hypothesis is based on differences in mechanical advantage of the respective manual procedures on multi-segmental versus short intervertebral muscles.

Skin Sympathetic Nerve Activity is Modulated during Slow Sinusoidal Linear Displacements in Supine Humans.

Low-frequency sinusoidal linear acceleration (0.08 Hz, ±4 mG) modulates skin sympathetic nerve activity (SSNA) in seated subjects (head vertical), suggesting that activation of the utricle in the peripheral vestibular labyrinth modulates SSNA. The aim of the current study was to determine whether SSNA is also modulated by input from the saccule. Tungsten microelectrodes were inserted into the common peroneal nerve to record oligounitary SSNA in 8 subjects laying supine on a motorized platform with the head aligned with the longitudinal axis of the body. Slow sinusoidal (0.08 Hz, 100 cycles) linear acceleration-decelerations (peak ±4 mG) were applied rostrocaudally to predominately activate the saccules, or mediolaterally to predominately activate the utricles. Cross-correlation histograms were constructed between the negative-going sympathetic spikes and the positive peaks of the sinusoidal stimuli. Sinusoidal linear acceleration along the rostrocaudal axis or mediolateral axis both resulted in sinusoidal modulation of SSNA (Median, IQR 27.0, 22-33% and 24.8, 17-39%, respectively). This suggests that both otolith organs act on sympathetic outflow to skin and muscle in a similar manner during supine displacements.

The influence of cervical spinal cord compression and vertebral displacement on somatosympathetic reflexes in the rat.

BACKGROUND CONTEXT: One theory within chiropractic proposes that vertebral subluxation in the upper cervical region induces spinal cord compression sufficient to alter spinal cord efferent output. We report on the feasibility of three different experimental approaches to test this theory. METHODS: A high threshold electrical-evoked somatosympathetic reflex was recorded in adrenal or renal nerves of 10 anaesthetized adult male rats before and after (1) graded pressure was applied directly to the C1/C2 spinal cord segment in eight rats by the use of either direct compression or inflation of an extradural balloon and (2) displacement, less than a dislocation applied posterior to anterior, to the C2 vertebra in two rats. The latency and amplitude of the pre- and postintervention reflex responses were compared. RESULTS: The reflex amplitude was not significantly changed by pressure (26 mmHg) from an extra-dural balloon or direct compression of the dura mater onto the dorsal spinal cord. Additional pressure, at least sufficient to occlude the dorsal vessels, induced a significant reduction in the amplitude of the reflex, and this reduction persisted for 20 minutes after removal of the pressure (Dunn's method for all pairwise multiple comparison Q stat=3.437; critical value for k=6 with α=0.05 is 2.936). Maximal vertebral (C2) displacement (4 mm), without dislocation did not induce significant changes compared with the control period. CONCLUSIONS: Although this feasibility study suggests it is unlikely that upper cervical vertebral subluxation, displacement less than a dislocation, compromises the sympathetic outflow in the adrenal or renal nerves, further vertebral displacement studies are necessary to formally test this.

Vestibular modulation of muscle sympathetic nerve activity during sinusoidal linear acceleration in supine humans.

The utricle and saccular components of the vestibular apparatus preferentially detect linear displacements of the head in the horizontal and vertical planes, respectively. We previously showed that sinusoidal linear acceleration in the horizontal plane of seated humans causes a pronounced modulation of muscle sympathetic nerve activity (MSNA), supporting a significant role for the utricular component of the otolithic organs in the control of blood pressure. Here we tested the hypothesis that the saccule can also play a role in blood pressure regulation by modulating lower limb MSNA. Oligounitary MSNA was recorded via tungsten microelectrodes inserted into the common peroneal nerve in 12 subjects, laying supine on a motorized platform with the head aligned with the longitudinal axis of the body. Slow sinusoidal linear accelerations-decelerations (peak acceleration ±4 mG) were applied in the rostrocaudal axis (which predominantly stimulates the saccule) and in the mediolateral axis (which also engages the utricle) at 0.08 Hz. The modulation of MSNA in the rostrocaudal axis (29.4 ± 3.4%) was similar to that in the mediolateral axis (32.0 ± 3.9%), and comparable to that obtained by stimulation of the utricle alone in seated subjects with the head vertical. We conclude that both the saccular and utricular components of the otolithic organs play a role in the control of arterial pressure during postural challenges.

Vestibulo-sympathetic responses.

Evidence accumulated over 30 years, from experiments on animals and human subjects, has conclusively demonstrated that inputs from the vestibular otolith organs contribute to the control of blood pressure during movement and changes in posture. This review considers the effects of gravity on the body axis, and the consequences of postural changes on blood distribution in the body. It then separately considers findings collected in experiments on animals and human subjects demonstrating that the vestibular system regulates blood distribution in the body during movement. Vestibulosympathetic reflexes differ from responses triggered by unloading of cardiovascular receptors such as baroreceptors and cardiopulmonary receptors, as they can be elicited before a change in blood distribution occurs in the body. Dissimilarities in the expression of vestibulosympathetic reflexes in humans and animals are also described. In particular, there is evidence from experiments in animals, but not humans, that vestibulosympathetic reflexes are patterned, and differ between body regions. Results from neurophysiological and neuroanatomical studies in animals are discussed that identify the neurons that mediate vestibulosympathetic responses, which include cells in the caudal aspect of the vestibular nucleus complex, interneurons in the lateral medullary reticular formation, and bulbospinal neurons in the rostral ventrolateral medulla. Recent findings showing that cognition can modify the gain of vestibulosympathetic responses are also presented, and neural pathways that could mediate adaptive plasticity in the responses are proposed, including connections of the posterior cerebellar vermis with the vestibular nuclei and brainstem nuclei that regulate blood pressure.

Visceral responses to spinal manipulation.

While spinal manipulation is widely seen as a reasonable treatment option for biomechanical disorders of the spine, such as neck pain and low back pain, the use of spinal manipulation to treat non-musculoskeletal complaints remains controversial. This controversy is due in part to the perception that there is no robust neurobiological rationale to justify using a biomechanical treatment of the spine to address a disorder of visceral function. This paper therefore looks at the physiological evidence that spinal manipulation can impact visceral function. A structured search was conducted, using PubMed and the Index to Chiropractic Literature, to construct of corpus of primary data studies in healthy human subjects of the effects of spinal manipulation on visceral function. The corpus of literature is not large, and the greatest number of papers concerns cardiovascular function. Authors often attribute visceral effects of spinal manipulation to somato-autonomic reflexes. While this is not unreasonable, little attention is paid to alternative mechanisms such as somato-humoural pathways. Thus, while the literature confirms that mechanical stimulation of the spine modulates some organ functions in some cohorts, a comprehensive neurobiological rationale for this general phenomenon has yet to appear.

Validity of the Doppler velocimeter in examination of vertebral artery blood flow and its use in pre-manipulative screening of the neck.

Pre-existing compromise of one or both vertebral arteries is considered a contraindication to neck manipulation. Current pre-manipulative screening tests may not adequately identify individuals with such compromise. It has been proposed that using a continuous wave ultrasound device (Doppler velocimeter) may assist in identifying patients presenting with flow abnormalities. The aim of this study was to determine the validity and reliability of the use of a velocimeter in detecting altered vertebral artery blood flow. Blood flow in the atlanto-axial segment of seated healthy adult volunteers (n=60) was examined in the neutral and end-range contralateral rotation positions. Duplex ultrasound scans were performed (n=58) and identified 17 volunteers (29.3%) with abnormal flow according to pre-determined criteria. Three trained physiotherapists blinded to the duplex examination results used a velocimeter to examine the vertebral arteries of the volunteers. The specificity of the velocimeter examination to detect abnormal flow identified by the duplex examination was fair to good (range 0.78-0.88). However, its sensitivity was poor (range 0.25-0.38) and the inter-examiner reliability was poor (kappa ranged from 0.15 to 0.26). This study suggests that the velocimeter may be neither a valid or reliable tool for the detection of abnormal blood flow in the vertebral arteries.

Pre-manipulative testing and the use of the velocimeter.

Manipulation of the cervical spine remains a common intervention for neck pain and dysfunction, despite the well-documented associated risk of vertebrobasilar stroke. The currently advocated pre-manipulative risk assessment protocols include the use of provocative positional tests to challenge the integrity of the vascular supply to the brain. This paper critically evaluates the validity of these pre-manipulative provocative tests in the light of ultrasonographic blood flow studies of the vertebral arteries. It also critically evaluates the evidence concerning the clinical utility of a portable continuous wave Doppler device (or velocimeter) to examine vertebral artery blood flow prior to neck manipulation. There is clear evidence that the provocative tests may produce both false positive and false negative findings. Initial research regarding the clinical use of a velocimeter suggests this device may provide a more objective assessment of vertebral artery blood flow than the provocative tests. However, the sensitivity, specificity and reliability of the use of the velocimeter in identifying abnormal vascular flow in the vertebral arteries, and therefore its clinical utility, has not yet been fully established.

Measurement of the vertebral canal dimensions of the neck of the rat with a comparison to the human.

The aim of this study was to determine the dimensions of the vertebral canal in the neck of the rat, because little is known about the morphology of the rat's cervical spine. A comparison then was made to the vertebral canal in the neck of the human. In part 1 of this study, we determined the precision of three different methods to measure the vertebral canal. The error (coefficient of variation) in these methods was found to range from 1 to 8%. In part 2, we used a computer-based system to measure digital images of the vertebra and determined the anterior to posterior and the transverse vertebral canal dimensions in the neck of 19 young adult Sprague-Dawley rats. The anterior to posterior dimension of the vertebral canal was greatest at the upper cervical (C1-C2) level and progressively decreased in the more caudal segments (C3-T1). The transverse dimension was greatest at the atlas (C1) vertebra and smallest at the axis (C2) vertebra with a steady increase in the transverse dimension with more caudal segments and a maximum transverse dimension at the level of the C6 and C7 vertebra. This study has demonstrated that the vertebral canal in the neck of young adult rats is similar in some regards to that of human. However, there are clear differences between the rat and human. These may be associated with differences in the morphology of the spinal cord or postural differences such as the cervicothoracic lordosis in bipeds compared with that in quadrupeds.

Modulation of muscle sympathetic bursts by sinusoidal galvanic vestibular stimulation in human subjects.

There is controversy as to whether the vestibulosympathetic reflexes demonstrated in experimental animals actually exist in human subjects. While head-down neck flexion and off-vertical axis rotation can increase muscle sympathetic nerve activity (MSNA) in awake subjects, we recently showed that bipolar galvanic vestibular stimulation (GVS) does not. However, it is possible that our stimuli (2 mA, 1 s)-although capable of causing strong postural and occulomotor responses-were too brief. To address this issue we activated vestibular afferents using continuous sinusoidal (0.5-0.8 Hz, 60-100 cycles, +/-2 mA) bipolar binaural GVS in 11 seated subjects. Sinusoidal GVS evoked robust vestibular illusions of "rocking in a boat" or "swinging from side to side." Cross-correlation analysis revealed a cyclic modulation of MSNA ranging from 31 to 86% across subjects (mean +/- SE 58 +/- 5%), with total MSNA increasing by 156 +/- 19% (P = 0.001). Furthermore, we documented de novo synthesis of sympathetic bursts that were coupled to the sinusoidal input, such that two bursts-rather than the obligatory single burst-could be generated within a cardiac interval. This demonstrates that the human vestibular apparatus exerts a potent facilitatory influence on MSNA that potentially operates independently of the baroreceptor system.

Absence of short-term vestibular modulation of muscle sympathetic outflow, assessed by brief galvanic vestibular stimulation in awake human subjects.

There is evidence in experimental animals for a potent vestibulosympathetic reflex, but its existence in humans is controversial. Static head-down neck flexion and off-vertical axis rotation have been shown to increase muscle sympathetic nerve activity (MSNA), but not skin sympathetic nerve activity (SSNA), whereas horizontal linear acceleration decreases MSNA in humans. However, both forms of stimuli also activate other receptors. To examine the effects of a pure vestibular stimulus on MSNA and SSNA, and its potential interaction with the baroreceptors, we used galvanic vestibular stimulation (GVS) in 12 healthy seated subjects. MSNA was recorded in ten subjects via a percutaneous microelectrode in the peroneal nerve; ECG, blood pressure, respiration, skin blood flow and sweating were also recorded. GVS (2 mA, 1 s pulse) was delivered via surface electrodes over the mastoid processes at unexpected times, triggered from the R-wave with a delay of 0, 200, 400 or 600 ms. In addition to causing robust postural illusions, GVS caused cutaneous vasoconstriction and sweat release in all subjects (due to a short-latency increase in SSNA, three subjects), but no significant change in MSNA. The failure of GVS to elicit a change in muscle sympathetic nerve activity, as documented by averaging, suggests that the vestibular system is not engaged in short-term modulation of muscle sympathetic activity. Conversely, phasic vestibular inputs do excite cutaneous sympathetic neurones, consistent with the observation that motion sickness is accompanied by pallor and sweating.