Philip S. Bolton

The ventrolateral medulla of the cat mediates vestibulosympathetic reflexes

Extracellular recordings were made from 94 neurons located in the ventrolateral medulla (VLM) whose firing rate was affected by vestibular nerve (VN) stimulation; 50 of these units were in the subretrofacial (SRF) nucleus, which contains cells that make direct excitatory connections with sympathetic preganglionic neurons. The sample included 12 SRF cells which were antidromically driven from the upper thoracic spinal cord and had conduction velocities of 10 m/s or less; the effect of VN stimulation on all but one of these units was inhibition. The onset latency of the response to VN stimulation was long [20.3 +/- 3.7 (S.E.M.) ms, n = 9, for the antidromically activated neurons and 12.1 +/- 1.2 ms, n = 73, for the others], suggesting that the effects were predominantly polysynaptic. In addition, most of the spontaneously active units tested (33/36) received convergent inputs from the carotid sinus nerve (CSN), as would be expected for neurons which influence sympathetic outflow. Vestibular-elicited inhibition of SRF neurons with projections to the intermediolateral cell column could account for late, long duration inhibition of sympathetic discharges produced by labyrinth stimulation.

Responses of neurons in the rostral ventrolateral medulla of the cat to natural vestibular stimulation.

To investigate the neural substrate of vestibulo-sympathetic reflexes, we studied the responses of neurons in the rostral ventrolateral medulla (RVLM) of decerebrate cats to natural stimulation of the labyrinth in vertical and horizontal planes. The RVLM is a major source of excitatory inputs to sympathetic preganglionic neurons. The animals used in these studies were baroreceptor-denervated and vagotomized and had a cervical spinal transection so that inputs from tilt-sensitive receptors outside of the labyrinth did not influence the units we recorded. Of the 38 neurons whose type of vertical vestibular inputs could be classified, the majority (27) received signals mainly from otolith organs. Only 4 of the neurons received inputs predominantly from vertical semicircular canals, and 7 were classified as having convergent inputs from otoliths and canals that were spatially aligned (2 cells) or misaligned (5 cells). In addition, only 2 of 68 neurons tested responded to sinusoidal horizontal rotations in a manner typical of brainstem neurons that receive inputs from the horizontal semicircular canals. Thus, the vestibular inputs to the RVLM appear to come mainly from otolith receptors. In labyrinthectomized cats, we were unable to locate neurons with responses to tilt similar to those of cells recorded in labyrinth-intact cats, confirming that the responses attributed to vertical vestibular inputs were produced by signals from the labyrinth. In animals whose semicircular canals had been rendered dysfunctional by plugging, we only recorded responses similar to those of neurons classified as having mainly otolith inputs in canal-intact animals, indicating that the dynamic behavior of these cells does not depend upon canal inputs. The presence of otolith inputs to the RVLM is consistent with the hypothesis that this region mediates vestibulo-sympathetic reflexes involved in correcting posturally-related changes in blood pressure.

Effects of deep and superficial experimentally induced acute pain on muscle sympathetic nerve activity in human subjects

Human studies conducted more than half a century ago have suggested that superficial pain induces excitatory effects on the sympathetic nervous system, resulting in increases in blood pressure (BP) and heart rate (HR), whereas deep pain is believed to cause vasodepression. To date, no studies have addressed whether deep or superficial pain produces such differential effects on muscle sympathetic nerve activity (MSNA). Using microneurography we recorded spontaneous MSNA from the common peroneal nerve in 13 awake subjects. Continuous blood pressure was recorded by radial arterial tonometry. Deep pain was induced by intramuscular injection of 0.5 ml hypertonic saline (5%) into the tibialis anterior muscle, superficial pain by subcutaneous injection of 0.2 ml hypertonic saline into the overlying skin. Muscle pain, with a mean rating of 4.9 ± 0.8 (s.e.m.) on a 0–10 visual analog scale (VAS) and lasting on average 358 ± 32 s, caused significant increases in MSNA (43.9 ± 10.0%), BP (5.4 ± 1.1%) and HR (7.0 ± 2.0%) – not the expected decreases. Skin pain, rated at 4.9 ± 0.6 and lasting 464 ± 54 s, also caused significant increases in MSNA (38.2 ± 12.8%), BP (5.1 ± 2.1%) and HR (5.6 ± 2.0%). The high‐frequency (HF) to low‐frequency (LF) ratio of heart rate variability (HRV) increased from 1.54 ± 0.25 to 2.90 ± 0.45 for muscle pain and 2.80 ± 0.52 for skin pain. Despite the different qualities of deep (dull and diffuse) and superficial (burning and well‐localized) pain, we conclude that pain originating in muscle and skin does not exert a differential effect on muscle sympathetic nerve activity, both causing an increase in MSNA and an increase in the LF : HF ratio of HRV. Whether this holds true for longer lasting experimental pain remains to be seen.

Spinal Manipulative Therapy and Somatosensory Activation

Manually-applied movement and mobilization of body parts as a healing activity has been used for centuries. A relatively high velocity, low amplitude force applied to the vertebral column with therapeutic intent, referred to as spinal manipulative therapy (SMT), is one such activity. It is most commonly used by chiropractors, but other healthcare practitioners including osteopaths and physiotherapists also perform SMT. The mechanisms responsible for the therapeutic effects of SMT remain unclear. Early theories proposed that the nervous system mediates the effects of SMT. The goal of this article is to briefly update our knowledge regarding several physical characteristics of an applied SMT, and review what is known about the signaling characteristics of sensory neurons innervating the vertebral column in response to spinal manipulation. Based upon the experimental literature, we propose that SMT may produce a sustained change in the synaptic efficacy of central neurons by evoking a high frequency, bursting discharge from several types of dynamically-sensitive, mechanosensitive paraspinal primary afferent neurons.

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.

Influences of neck afferents on sympathetic and respiratory nerve activity.

It is well established that the vestibular system influences the sympathetic nervous system and the respiratory system; presumably, vestibulosympathetic and vestibulorespiratory responses participate in maintaining stable blood pressure and blood oxygenation during movement and changes in posture. Many brainstem neurons that generate vestibulospinal reflexes integrate signals from the labyrinth and neck muscles to distinguish between head movements on a stable body and whole body movements. In the present study, responses were recorded from the splanchnic (sympathetic), hypoglossal (inspiratory) and abdominal (expiratory) nerves during stimulation of the C2 dorsal root ganglion or C2 or C3 nerve branches innervating dorsal neck muscles. Stimulation of neck afferents using low current intensities, in many cases less than twice the threshold for producing an afferent volley recordable from the cord dorsum, elicited changes in sympathetic and respiratory nerve activity. These data suggest that head rotation on a stable body would elicit both cervical and vestibular inputs to respiratory motoneurons and sympathetic preganglionic neurons. The effects of cervical afferent stimulation on abdominal, splanchnic and hypoglossal nerve activity were not abolished by transection of the brainstem caudal to the vestibular nuclei; thus, pathways in addition to those involving the vestibular nuclei are involved in relaying cervical inputs to sympathetic preganglionic neurons and respiratory motoneurons. Transection of the C1-3 dorsal roots enhanced responses of the splanchnic and abdominal nerves to pitch head rotations on a fixed body but diminished responses of the hypoglossal nerve. Thus, neck and vestibular afferent influences on activity of respiratory pump muscles and sympathetic outflow appear to be antagonistic, so that responses will occur during whole body movements but not head movements on a stationary trunk. In contrast, neck and vestibular influences on tongue musculature are complementary, presumably to produce tongue protrusion either during movements of the head alone or of the whole body.

Responses of neurons in the caudal medullary raphe nuclei of the cat to stimulation of the vestibular nerve

SummaryIn the decerebrate cat, recordings were made from neurons in the caudal medullary raphe nuclei to determine if they responded to electrical stimulation of the vestibular nerve and thus might participate in vestibulo-sympathetic reflexes. Many of these cells projected to the upper thoracic spinal cord. The majority (20/28) of raphespinal neurons with conduction velocities between 1 and 4 m/s received vestibular inputs; 13 of the 20 were inhibited, and 7 were excited. Since many raphespinal neurons with similar slow conduction velocities are involved in the control of sympathetic outflow, as well as in other functions, these cells could potentially relay vestibular signals to sympathetic preganglionic neurons. The onset latency of the vestibular effects was long (median of 15 ms), indicating the inputs were polysynaptic. In addition, 34 of 42 raphespinal neurons with more rapid conduction velocities (6–78 m/s) also received long-latency (median of 10 ms) labyrinthine inputs; 26 were excited and 8 were inhibited. Although little is known about these rapidlyconducting cells, they do not appear to be involved in autonomic control, suggesting that the function of vestibular inputs to raphe neurons is not limited to production of vestibulosympathetic reflexes. One hypothesis is that raphe neurons are also involved in modulating the gain of vestibulocollic and vestibulospinal reflexes; this possibility remains to be tested.

Reflex effects of vertebral subluxations: the peripheral nervous system. An update

Abstract Background: The traditional chiropractic vertebral subluxation hypothesis proposes that vertebral misalignment cause illness, disease, or both. This hypothesis remains controversial. Objective: To briefly review and update experimental evidence concerning reflex effects of vertebral subluxations, particularly concerning peripheral nervous system responses to vertebral subluxations. Data source: Information was obtained from chiropractic or, scientific peer-reviewed literature concerning human or animal studies of neural responses to vertebral subluxation, vertebral displacement or movement, or both. Conclusion: Animal models suggest that vertebral displacements end putative vertebral subluxations may modulate activity in group I to IV afferent nerves. However, it is not clear whether these afferent nerves are modulated during normal day-to-day activities of living end, if so, what segmental or whole-body reflex effects they may have. (J Manipulative Physiol Ther 2000;23:101–3)

Commissural neurons in the cat upper cervical spinal cord

WE have begun a study of the intrinsic circuitry of the cats upper cervical cord, in part to elucidate the role of spinal interneurons in vestibulocollic reflexes. Using retrograde labelling with Fluoro-Gold and intra-spinal microstimulation, we have identified commissural neurons projecting to the contralateral ventral horn. Neurons tended to be in the medial half of lamina VIII. Approximately half of the neurons were propriospinal neurons that could be activated antidromically from the rostral border of the cervical enlargement. Most of the tested, spontaneously active neurons were driven by stimulation of the ipsi- and/or contralateral vestibular nerve, in some cases disynaptically.

A descriptive study of the force and displacement profiles of the toggle-recoil spinal manipulative procedure (adjustment) as performed by chiropractors

The aim of this study was to determine the variability of the thrust parameters produced by practitioners performing a high velocity spinal manipulative therapy technique (toggle-recoil) normally applied to the neck. Fourteen participants performed three thrust trials, separated by >30minutes, on a patient simulation device. Force and displacement generated during the thrusts were simultaneously recorded and analysed off line. Peak thrust force ranged from 18.2 to 246N with a mean of 111.2N (SD 48.8). Time to peak thrust force ranged from 20 to 100ms, mean 67.5 ms (SD 13.1). Peak thrust displacement ranged from 6.1 to 28.9mm, mean 24.1mm (SD 4.9) and time to peak thrust displacement ranged from 22.5 to 105ms, mean 59.4ms (SD 13.8). This study demonstrates that the force and displacement induced by any individual practitioner on a simulator can vary by up to 50% during a toggle-recoil thrust. Furthermore, different practitioners may vary in their force by as much 100% and in displacement by 50% when the toggle-recoil spinal manipulative procedure is performed.