Human Studies Related to the Autonomic Nervous System
An informed understanding of the structure and function of the autonomic nervous system is important to the effective practice of the individual chiropractic clinician and to the development of the discipline of chiropractic. At a superficial level, it is widely theorized that reflexes mediated via the autonomic nervous system are probably the primary mechanisms by which subluxation and adjustment may affect the function of the internal organs. That is not to say that they are the only mechanisms because other neurologic mechanisms and also nonneurologic mechanisms have the capacity to modify organ function in response to somatic stimulation. However, somatoautonomic reflexes provide what are thought to be the dominant forces.
It is therefore absolutely essential that the practitioner understand the potential relationships between somatic stimulation and autonomic function, that they are equipped to monitor autonomic function and diagnose autonomic dysfunction, and that they understand the implications that treatments at their disposal hold for somatoautonomic interactions. For the discipline of chiropractic, an understanding of autonomic structure and function is essential to the design, execution, and interpretation of clinical studies. Such understanding also provides the principal scientific rationale for the extension of chiropractic adjusting beyond musculoskeletal care.
Having defined what could be achieved with an intelligent understanding of the autonomic nervous system, and to consider what steps the chiropractic profession might wish to take with respect to this area of science, it would be worth examining the present status of our knowledge base. With particular reference to research of interest to the discipline of chiropractic, knowledge up to the mid 1990s was exquisitely synthesized in the landmark monograph of Sato et al  published in 1997. This volume particularly emphasized basic physiologic work, particularly animal experimentation, which formed the bulk of work in autonomic neuroscience up until that time. Consequently, only 3 of approximately 750 studies cited in the monograph by Sato et al made reference to the effects of spinal stimulation, and all of these were animal studies.
In the past quarter century, however, tremendous advances have been made in the noninvasive measurement of autonomic function, such that experiments which previously could only be performed in anesthetized animals can now be replicated and exceeded in human subjects. In addition, the appreciation of the role of the autonomic nervous system in such common and important diseases such as diabetes and chronic heart failure has led to enormous growth in clinically oriented research. This is manifested in the large numbers of research articles published and in such concrete indicators as the founding of the journal Clinical Autonomic Research and in the renewal of the Journal of the Autonomic Nervous System as Autonomic Neuroscience: Basic and Clinical. Since the publication of the last white paper, certainly, thousands of research articles of relevance to chiropractic have been published. The challenge for the chiropractic profession is in accessing, understanding, and applying this knowledge. A relatively small number of articles pertaining to autonomic neuroscience are directly concerned with chiropractic interventions. These article, which are most patently relevant to SM, will now be summarized.
Articles written by chiropractors and related to autonomic neuroscience have tended to focus on the use of SM in the relief of visceral complaints, on the reasonable assumption that any observed therapeutic effects are mediated by the autonomic nervous system. Logically, this research has focused on cardiovascular function, which is relatively easy to monitor, of profound clinical importance, and the primary target of short-term autonomic behavior. In addition, it is assumed to be relatively easy to extrapolate from measures of cardiovascular function to autonomic nervous system behavior.
Until a decade ago, virtually all discussion of autonomic involvement in chiropractic interventions was based on small studies — often case studies or series of patients. Indeed, with older articles in the health sciences in general, there may have been a tendency to mix large doses of hypothesis with rather miserly portions of original data. One article described a patient with premature ventricular contractions who was treated with SM.  Case reports [363–365] have also referred to positive effects in hypertension. Another article referred to 2 patients who received SM for the treatment of hypercholesterolemia. 
Several clinical studies have previously examined the effects of SM on blood pressure and heart rate in conscious humans to draw conclusions about physiologic regulation. Tran and Kirby [367, 368] reported that neither cervical SM (with the subject supine) nor upper thoracic SM (with the subject prone) had any effect on heart rate in small cohorts of healthy young adults. They did report small changes in systolic and diastolic blood pressure. However, these proposed effects are not supported by statistical analysis of their raw data — the authors only gave their impression of the general trend in blood pressure readings. An additional problem is that the authors did not give the time frame over which pre- and posttreatment measurements were taken, that is, seconds, minutes, or hours before and after treatment. Hood  reported that with chiropractic treatment and lifestyle modification, 75 patients who previously had high or low blood pressure, subsequently had readings closer to the norm. It is unclear from the written report whether the trial was prospective or retrospective, nor is it clear when blood pressure readings were taken in relation to treatment. Hence, the effects described may be nothing more than a demonstration of regression toward the mean.
McKnight and DeBoer  reported statistically significant decreases in systolic and diastolic blood pressure in a cohort of 53 healthy young college students (versus no significant changes in a control cohort of 22 subjects). The treatment applied was a cervical manipulation with the subject sitting. Blood pressure was measured by sphygmomanometry within the few minutes before treatment and within the 1 minute after treatment. On the other hand, Nansel et al  detected no responses in blood pressure and heart rate to sitting cervical SM in healthy young adults when comparing measures taken 15 minutes or more before treatment and 5 minutes or more after treatment. Yates et al  reported statistically significant decreases in systolic and diastolic blood pressure in a small cohort of mildly hypertensive patients receiving a single upper thoracic manipulation applied with a mechanical percussive device. Blood pressure was measured with a sphygmomanometer before and “immediately after” treatment. The effects of authentic manipulation could not be shown using placebo or sham treatments. However, there was no follow-up of patients beyond the day of treatment.
Knutson  reported on a cohort of patients (including normotensives and hypertensives) who received SM for “upper cervical joint dysfunction.” With blood pressure measured in the few minutes before and within 2 minutes after treatment, there was a significant decline in systolic, but not diastolic, blood pressure. There was no follow-up after the single treatment. In a small pilot study  examining the effects of SM vs massage in subjects with essential hypertension, small declines in systolic and diastolic pressure were seen over the course of several months, with the greatest effects achieved in the control (no treatment) group. No statistical comparison was made for effect size in this pilot study. A study by Goertz et al  showed that the addition of SM to dietary management did not improve outcomes (decreases in systolic and diastolic pressure at ~4 weeks) for subjects with “high-normal blood pressure or stage 1 hypertension.” Either the authors themselves or those who have subsequently interpreted these various studies have been inclined to speculate that increases in heart rate and blood pressure reflect increases in cardiac sympathetic output or, conversely, withdrawal of vagal output. In fact, better markers of autonomic function exist as do better markers of cardiovascular health.
None of these relatively few studies in healthy and hypertensive subjects report significant long-term effects on systolic or diastolic blood pressure. On the other hand, some studies have found statistically significant effects for cervical and thoracic manipulation in the few minutes immediately after treatment. This might have been predicted by reference to basic knowledge of autonomic function, which should have been referenced in designing these studies. An additional design problem with virtually all physiologic and clinical studies published until the late 1990s concerning SM and cardiovascular function lies in the methods of subject monitoring. In all instances cited, the investigators have relied on sphygmomanometry to measure blood pressure. In as much as this technique is inappropriate for continuous monitoring of blood pressure, and blood pressure fluctuates continuously in the conscious subject, most studies published so far on the short-term effects of SM on blood pressure have little credibility. Unlike conventional sphygmomanometry, arterial tonometry is appropriate for the continuous measurement of cardiovascular function during SM.  However, this rather expensive technology has found only limited application in chiropractic studies. 
Chiu and Wright  used skin conductance and skin temperature changes to infer responses of cutaneous sympathetic efferents to cervical mobilization. These results were consistent with cardiovascular effects reported separately.  This group has also looked at skin conductance and skin temperature responses to peripheral joint manipulation  and physiologic responses to cervical manipulation in patients with lateral epicondylalgia  and cervical pain.  This is an exceptional instance of a team of researchers progressively pursuing the neurophysiologic effects of manipulation, allowing them to refine their experimental technique and to develop robust hypotheses to explain their results.
Notwithstanding the successes of the University of Queensland team cited above, a technology that perhaps deserves more attention in investigations of SM involves the computation of cardiac autonomic output from electrocardiographic recordings. This technology is based on the understanding that heart rate is regulated on a beat-to-beat basis by a short feedback loop, which involves peripheral baroreceptors, brain stem nuclei and autonomic cardiac efferent fibers. An increase in the discharge rate of cardiovascular baroreceptors, as what occurs with increases in blood pressure, results in a reflex inhibition of sympathetic output to the cardiovascular system as well as an increase in cardiac vagal activity and, so, a decrease in heart rate. It is thought that the primary homeostatic purpose of this feedback system is to maintain mean arterial blood pressure around an optimal “set point,” allowing that the “set point” may vary in the long and short term, both in health and because of disease.  However, the increase in heart rate, which accompanies inspiration, probably also serves a role in increasing respiratory efficiency.  Noxious input and, so, activation of the periaqueductal gray matter tends to dampen baroreflexes.
Rhythmic oscillations in intrathoracic pressure, imposed by the respiratory cycle, modulate the normal fluctuations in blood pressure that result from the cardiac cycle. Hence, via the baroreflex, the respiratory rate entrains rhythmic variation of heart rate. This oscillation in heart rate, known as the respiratory sinus arrhythmia, is largely attributable to vagal (parasympathetic) activity in conscious humans at rest or during low levels of physical activity.  Somewhat slower intrinsic oscillations in sympathetic preganglionic neuron activity may result in subsequent superimposition of an additional low-frequency oscillation on blood pressure and heart rate. The result is a literally chaotic variation in cardiac rhythm resulting from the complex interaction of reflexes mediated by vagal and sympathetic cardiac efferents. The relative roles of the sympathetic and parasympathetic systems in heart rate variability (HRV) differ between species according to the access of different efferents to the myocardium and to the electrical conduction system of the heart. The physiologic contributions of the sympathetic and parasympathetic nerves and their anatomical details are of enormous importance in the surgical management of cardiac disease (see, eg, Ref. ), and probably have implications for responses to more benign somatic stimuli as well, including subluxation and adjustment.
Studies using HRV to derive measures of autonomic responses to SM and mobilization are beginning to be conducted. Only 1 article has reported a controlled study of the effects of SM on HRV.  This article showed that SM was associated with increases in cardiac sympathetic output and in the balance of sympathetic to parasympathetic flow to the heart, notwithstanding decreases in heart rate. Additional studies yet to be published corroborate these effects. These physiologic studies in well subjects have subsequently led to a pilot investigation in cardiac patients.
If one examines the modern history of investigations of the effects of SM on autonomic function, an ironic picture emerges. The earlier studies tended to focus on clinical outcomes from which conclusions concerning neurophysiology were extrapolated. Considering the results of more recent studies, these conclusions seem to have been largely mistaken. The technology used in earlier studies was largely inappropriate to the experimental questions being asked. In the past 10 years, there has been a shift to more appropriate technologies, which have been applied first in physiologic studies of well subjects and only later in studies of patients. These are, of course, very positive developments, although there is still a large gap between the cutting edge of technology (and knowledge) and investigations of SM.
Initiate a program to educate the educators, beginning with heads of programs, including academics in research, neurosciences, and chiropractic principles. The Research Agenda Conference meetings serve this objective in part. However, the concentrated nature of these meetings does not allow justice to be done to the wealth of possibilities that chiropractic could be exploring in neuroscience research.
A body, or bodies, should be entrusted to develop a current curriculum, which would serve as a common resource for all chiropractic educational programs. This is not to imply that all colleges should be teaching the same content. However, it is a significant challenge for some faculty to access reliable “chirocentric” resources in the neurosciences. There seems little reason to not have faculties cooperating on developing a shared resource.
A funding mechanism needs to be created to identify and support autonomic research of importance to chiropractic. Research funding decisions must be based first and foremost on scientific rigor.
The profession should create an endowed chair in autonomic research. This should be in an environment best equipped to produce research of the highest quality, to mentor young researchers, and to contribute to the common body of knowledge of the health sciences. This may possibly be in a chiropractic educational institution, but a university or free-standing research institution should also be considered.
The literature summaries of the 6 topic sections (anatomy, biomechanics, somatic nervous system, animal models, immune system, and human studies related to the autonomic nervous system) indicated that a significant body of basic science research evaluating chiropractic spinal adjusting has been completed and published since the 1997 basic science white paper. Much more basic science research in these fields needs to be accomplished, and the recommendations at the end of each topic section should help researchers, funding agencies, and other decision makers develop specific research priorities.
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