SHORT-TERM EFFECTS OF MANIPULATION TO THE UPPER

THORACIC SPINE OF ASYMPTOMATIC SUBJECTS ON PLASMA

CONCENTRATIONS OF EPINEPHRINE AND NOREPINEPHRINE—
A RANDOMIZED AND CONTROLLED OBSERVATIONAL STUDY
Aaron A. Puhl, MSc, a and H. Stephen Injeyan, MSc, PhD, DC b

ABSTRACT

Objective: The purpose of this study was to investigate the short-term effects of spinal manipulation applied to a
hypomobile segment of the upper thoracic spine (T1-T6), on plasma concentrations of norepinephrine (NE) and
epinephrine (E) in asymptomatic subjects, under strictly controlled conditions.
Methods: Fifty-six asymptomatic subjects were randomly assigned to receive either a chiropractic manipulative
intervention or a sham intervention in the upper thoracic spine. A 20-gauge catheter fitted with a saline lock was used
to sample blood before, immediately after, and 15 minutes after intervention. Plasma NE and E concentrations were
determined using an enzyme-linked immunosorbent assay. Changes in plasma catecholamine concentrations were
analyzed within and between groups using 1- and 2-sample t tests, respectively.
Results: The plasma samples of 36 subjects (18 treatment, 18 control) were used in the analysis. Mean plasma
concentrations of NE and E did not significantly differ between the 2 groups at any time point and did not change
significantly after either the manipulative or sham intervention.
Conclusions: The results of this study indicate that a manipulative thrust directed to a hypomobile segment in the
upper thoracic spine of asymptomatic subjects does not have a measurable effect on the plasma concentrations of
NE or E. These results provide a baseline measure of the sympathetic response to spinal manipulation. (J Manipulative
Physiol Ther 2012;35:209-215)
Key Indexing Terms: Musculoskeletal Manipulations; Autonomic Nervous System; Norepinephrine; Epinephrine

pinal manipulative therapy (SMT) is a common clinical benefits of SMT, it does hinder acceptance by the

S treatment modality used in a variety of manual

medicine disciplines. There is an ever-increasing
body of clinical evidence that supports the use of SMT in
the treatment of low back pain, 1 neck pain, 2 headaches, 3
and other neuromusculoskeletal conditions. 4 Many non-
specific, nonmusculoskeletal responses have also been
reported 5; however, the full range of therapeutic benefits of
SMT and the exact biologic mechanism(s) of its therapeutic
effects remain unclear. Although this does not negate the
a
Chiropractic Intern, Canadian Memorial Chiropractic College,
Toronto, Ontario, Canada.
b
Professor and Chair, Department of Pathology and Microbi-
ology, Canadian Memorial Chiropractic College, Toronto,
Ontario, Canada.
Submit requests for reprints to: H. Stephen Injeyan, MSc, PhD,
DC, Professor and Chair, Department of Pathology and Microbi-
ology, Canadian Memorial Chiropractic College, 6100 Leslie St,
Toronto, ON, M2H 3J1 (e-mail: sinjeyan@cmcc.ca).
Paper submitted June 17, 2011; in revised form October 20,
2011; accepted October 27, 2011.
0161-4754/$36.00
Copyright © 2012 by National University of Health Sciences.
doi:10.1016/j.jmpt.2012.01.012
scientific and health care communities more broadly as well
as encumber attempts to improve the practice of SMT. One
idea common to many theories is that changes in the normal
anatomical, physiologic, or biomechanical dynamics of
contiguous vertebrae can adversely affect the functioning of
the nervous system, and SMT has been suggested to correct
these changes. 6 In this regard, the current model of
somatoautonomic reflex provides 1 potential link between
spinal manipulation, the autonomic nervous system (ANS),
and various physiologic effects. 7
The relevance of the somatoautonomic reflex theory to
chiropractic philosophers is reliant on the idea that sensory
input from spinal or paraspinal tissues can influence bodily
processes by affecting the ANS. Indeed, several experi-
ments performed with animal models have indicated a link
between noxious chemical stimulation to paraspinal tissues
and somatoautonomic reflexes. 8-12 In these studies, nox-
ious chemical stimulation of paraspinal tissues appeared to
produce an excitatory effect on sympathetic activity.
Studies examining the effect of mechanical stimulation of
spinal joints on autonomic and visceral function in animal
models have also been conducted. 13-15 These examinations

209
210 Puhl and Injeyan Journal of Manipulative and Physiological Therapeutics
Sympathetic Effects of Spine Manipulation March/April 2012

suggest that when different spinal segments are mechani- examine the effect of manipulation to other regions of the
cally stimulated, this can produce qualitatively and spine and also take strict measures to control for sources of
quantitatively different responses, depending on the area error. The objective of this study was to examine the short-
being stimulated. term effects of SMT to hypomobile segments of the upper
In addition to basic animal model studies, experiments thoracic spine (T1-T6) of asymptomatic subjects on plasma
examining the reflex effects of mechanical stimulation to levels of NE and E under strictly controlled conditions.
spinal and paraspinal tissues of human subjects are also well
documented. Researchers have provided evidence that
SMT can result in measurable changes to distal skin METHODS
temperature, 16-19 cutaneous electrical conductance, 19,20 Subjects
cutaneous blood flow, 21 respiratory function, 22 heart rate
Posters, email, and word of mouth were used to recruit a
and blood pressure, 23-25 pupillary light reflexes, 26,27 and
convenience sample of 56 subjects from the staff and
inflammatory and immune responses. 28-30 Although such student body of the Canadian Memorial Chiropractic
reports may be representative of what may occur in the College as well as their friends and relatives. Subjects
clinical setting, only a limited amount of research into the
were offered a $20 cash incentive for their time and
exact underlying mechanisms has been done. For example,
contribution to the study. Subjects were given all
data stemming from animal studies suggest that neurologic
information about exclusion criteria at the time of
mechanisms may underlie these effects, likely being
recruitment and then reminded of the relevant criteria at
mediated by way of the sympathetic nervous system
24 to 36 hours before their arranged time of participation.
(SNS). Unfortunately, the research connecting the phe-
Subject inclusion was limited to individuals between 20
nomenological responses documented in human studies, and 45 years old. Because we were examining an
such as those mentioned above, with the neurophysiolog- asymptomatic population, subjects who had experienced
ically demonstrated somatoautonomic reflexes from animal
any back pain (including neck or upper back pain) or who
studies is limited.
had experienced any type of illness in the past 1 week were
Physiologic processes under the control of the SNS are
excluded from the study. Furthermore, subjects were
modulated by the local release of norepinephrine (NE) from
excluded if they had a history of hemophilia or any major
nonsynaptic, postganglionic sympathetic terminals and
disease that could potentially affect the spine or SNS,
circulating epinephrine (E) secreted by the adrenal medulla.
including neoplasms, cardiovascular, and endocrine dis-
It is known that the predominant sources of circulating NE eases. Those who were pregnant, had used tobacco
and E in humans are sympathetic nerve endings and the products, and/or had started taking any newly prescribed
adrenal medulla, respectively; that plasma catecholamine
medications within the last 1 month; had any surgery or
levels change in a matter of seconds in response to
major injury in the previous 1 month; had engaged in
sympathetic stimulation 31; and that the measurement of
isometric and isotonic exercise, reported experiencing
plasma concentrations of NE and E is an accepted method
major psychologic stress, or had consumed caffeinated
of gauging overall sympathetic and adrenal medullary
food and/or beverage products within the previous 24
activity. 32-34 Moreover, observed changes in the plasma
hours; or had consumed any food or beverage product
concentrations of NE and E are often sufficient to
(except water) within the previous 2 hours were also
differentiate the activity of these 2 sources because only
excluded from the study. Subjects were also excluded if
2% to 7.5% of circulating NE, as opposed to most of
they had received any manual therapy including SMT,
circulating E in peripheral blood, is derived from the
massage therapy, or acupuncture within the previous 1
adrenal medulla. 35
month. Finally, subjects were excluded if the clinician
To date, there has been only 1 small, nonrandomized study
could not find any hypomobile segments in the upper
examining the effect of SMT on plasma levels of NE and E. 36
thoracic spine (T1-T6) or if the catheter could not be
The study suggested that there were no measurable changes
successfully inserted into the subject's left cubital vein on
to plasma NE or E in response to a high-velocity, low-
the first attempt.
amplitude rotatory thrust to the lower cervical spine when
The final decision with regard to inclusion of a subject
compared with a sham intervention in asymptomatic subjects.
into the study was made by the study clinician after an
However, it is possible that the lack of a demonstrable change
interview and review of the inclusion/exclusion criteria but
in the concentrations of these catecholamines was due to
before randomization.
limitations in experimental protocol. There is documented
evidence of changes to autonomically regulated processes in
humans, in response to thoracic manipulation, 16,25,28,30 and Study Protocol
animal and human studies have both suggested that there can This observational study used a parallel group, random-
be differences in response, depending on the spinal level ized, and controlled design. A single treating clinician with
being stimulated. 16,37 Thus, it is important that studies 26 years of chiropractic clinical experience examined all
Journal of Manipulative and Physiological Therapeutics
Volume 35, Number 3
participants using static and motion palpation procedures to
assess for hypomobile spinal motion segments in the upper
thoracic spine (T1-T6). Hypomobile segments were marked
with an X on the skin to facilitate their relocation when
appropriate. Those participants with at least 1 hypomobile
segment were randomized by the treating clinician and then
prepared for phlebotomy by a registered nurse blinded to the
participant's allocation. A 20-gauge intravenous catheter
(REF 381234; BD Insyte, Franklin Lakes, NJ) fitted with a
saline lock (2N8378; Baxter, Mississauga, ON) was inserted
in the subject's left median cubital vein. Then, participants
were instructed to lie prone on a treatment table in a
comfortable position and to rest quietly and motionless for
the duration of the study. After a 10-minute equilibration
period, a 4-mL resting blood sample was collected. The
treating clinician then applied the manipulative or control
intervention to a marked segment, immediately after which
another 4-mL blood sample was collected. After a 15-
minute rest period, a final 4-mL blood sample was collected,
and the catheter was removed from the participant.
This study protocol was approved by Canadian Memo-
rial Chiropractic College Research Ethics Board. Informed
consent was obtained in writing after the procedure had
been fully explained. One to 3 participants were tested per
day and always between the times of 10 AM and 12 PM.
Samples of venous blood were collected from the
intravenous line into chilled vacutainers containing
EDTA. A peripheral intravenous line was used because
this has been shown to yield accurate analyte levels 38 and
avoided the confounding factor of multiple needles.
Immediately before each sampling, 3 mL of blood was
drawn and discarded to clear the catheter of any saline.
Immediately after each sampling, the catheter was flushed
with 3 mL of a 0.9% sterile saline solution to maintain
patency. All blood samples were placed on ice immediately
after collection. The registered nurse recorded any adverse
events from the beginning of the protocol until 10 minutes
after removal of the catheter.
Blinding and Randomization
Participants were randomly assigned to either the
treatment or control group using a lottery method. Equal
sex distribution was ensured by using 2 sets of randomly
assorted folded paper tickets containing allocation status,
one set for each sex, prepared before the study. Participants
were asked to choose a ticket from the set of their respective
sex and give it to the treating clinician. Participants were not
permitted to view the contents of the ticket, thus ensuring
that participants remained blinded until after they actually
received the manipulation or the control intervention. The
allocation of each participant was recorded by the treating
clinician using a key that was also used to label the blood
samples; this allowed blinding of the laboratory investigator
to the source of each blood sample. The subject allocation
Puhl and Injeyan 211
Sympathetic Effects of Spine Manipulation
and number assignment were kept in a secured drawer by
the treating clinician; the code was broken after the
conclusion of the laboratory analysis to allow for grouping
and statistical analysis.
Intervention and Control Procedures
The manipulative intervention consisted of a combina-
tion type adjustment (hypothenar transverse push) directed
to the previously identified hypomobile spinal segment
between T1 and T3 or a Carver-Bridge type adjustment
(bilateral hypothenar push) for segments T4 to T6. 39 The
participant was instructed to breathe in deeply and then
exhale at a natural rate before the application of the
manipulative intervention. The occurrence of an audible
cavitation was noted but not required. Control participants
were treated in an identical manner with regard to hand
contact and breathing instructions, except there was no
application of a thrust by the treating clinician.
Laboratory Procedures
Blood samples were kept on ice from the moment of
sampling until laboratory processing. Blood samples were
centrifuged for 10 minutes at 3000 rpm in a refrigerated
centrifuge within 30 minutes of sampling. Plasma was
removed from the packed cell fraction and stored at −80°C
for later analysis. Plasma NE and E concentrations were
determined using an enzyme immunoassay kit (2-Cat
ELISA; BA 10-1500; Labor Diagnostika Nord, Nordhorn,
Germany) and an enzyme-linked immunosorbent assay
reader (450 nm) according to the supplied protocol. All
samples were run in duplicate.
Statistical Analysis
Appropriate descriptive statistics (mean and SD) were
used to characterize the subjects' demographic data.
Demographic profiles between the treatment and control
groups were compared using 2-sample, 2-tailed t tests or χ 2
analysis. Baseline and subsequent measures of NE and E
between the treatment and control groups were compared
using a 2-sample, 2-tailed t test. For every subject, samples
collected before intervention served as a self-control
(baseline) to which postintervention responses were
compared. The mean difference between preintervention
and postintervention NE and E concentrations was
determined within the treatment and control groups and
then analyzed using a 1-sample t test. The mean difference
between preintervention and postintervention NE and E
concentrations between the treatment and control groups
was also determined and compared using a 2-sample, 2-
tailed t test. The standard for statistical significance in all
analyses was P less than .05.
212 Puhl and Injeyan
Sympathetic Effects of Spine Manipulation
Fig 1. Study flow diagram.
RESULTS
Fifty-six volunteers were accepted into the study and
randomized: 26 treatment subjects and 30 control subjects
(Fig 1). Of those, the plasma samples of 36 subjects (18
treatment, 18 control) were used in the final analysis.
Fourteen subjects (7 treatment, 7 control) became ineligible
postrandomization because of unsuccessful first attempts at
insertion of the catheter into the left cubital vein. Two
subjects (both control) were excluded from the study
postrandomization due to an adverse reaction; both subjects
reported feeling vertigo after insertion of the catheter. Two
subjects (1 intervention, 1 control) were omitted from the
data set postrandomization because of movement during the
study, and 2 subjects (both control) were omitted because of
excessive hemolysis of their samples, which could have
interfered with laboratory analysis. No immediate or short-
term adverse events were recorded after the manipulative or
control interventions.
Demographic profiles did not significantly differ be-
tween the 2 groups with regard to number of males, mean
age, or mean time since last SMT (Table 1). Mean plasma
concentrations of NE and E did not significantly differ
between the 2 groups at baseline or at either of the
postintervention sample times and did not change signif-
icantly over the course of the study (Tables 2 and 3).
DISCUSSION
A multitude of physiologic responses to spinal manip-
ulation/mobilization are documented in the literature, and
there are various theories under consideration to explain
these phenomena. A recent systematic review found
sufficient evidence from human studies to support the
Journal of Manipulative and Physiological Therapeutics
March/April 2012
existence of a neurophysiologic model. 40 Indeed, many
chiropractic philosophers have long considered that such
changes may be mediated by way of the ANS, but there still
exists a void in the literature for basic studies with human
subjects that evaluate possible explanations for the
extensive phenomenological evidence using data for
primary indicators of sympathetic activity.
The measurement of plasma concentrations of NE and
E is an accepted method of gauging overall sympathetic
and adrenal medullary activity, and plasma catecholamine
levels are known to change in a matter of seconds in
response to sympathetic stimulation. 31-34 We sought to
evaluate whether the plasma concentrations of NE and E
would change as a direct result of a manipulative thrust to
the upper thoracic spine of asymptomatic subjects. This
could occur under 2 hypotheses: (1) that mechanical
stimulation to the upper thoracic spine causes a short-
term, reflexive alteration in sympathetic outflow or 2) that
hypomobility between segments in the thoracic spine of
asymptomatic subjects can result in an altered basal level of
sympathetic outflow that may be corrected with a
manipulative thrust. Indeed, there is ample documented
evidence of changes to autonomically regulated processes
in asymptomatic human subjects, in response to thoracic
manipulation. 16,25,28,30 However, this study was unable to
detect any immediately measurable change in plasma
concentrations of NE or E after a manipulation to a
hypomobile segment and thus did not support either
hypothesis. These results are consistent with a previous
small, nonrandomized study that observed no measurable
effect of cervical manipulation on plasma levels of NE and
E. 36 These results are also consistent with a recent study
that observed no change in pupil responsiveness, an indirect
measure of the balance between the sympathetic and
Journal of Manipulative and Physiological Therapeutics Puhl and Injeyan 213
Volume 35, Number 3 Sympathetic Effects of Spine Manipulation

Table 1. Demographic characteristics of subjects

Control group Treatment group P
n 18 18
No. of males 11 8 .32
Mean age in years (SEM) 25.9 (1.0) 26.4 (1.1) .74
Mean time since last SMT in days (SEM) 191.9 (74.5) 249.7 (88.9) .62

Table 2. Plasma concentrations of norepinephrine before and after a single manipulative thrust to the upper thoracic spine
Before After a Change a Pa After b Change b Pb
Control 1.57 (0.15) 1.59 (0.14) 0.08 (0.09) .38 1.64 (0.17) 0.06 (0.12) .61
Treatment 1.52 (0.17) 1.55 (0.19) 0.02 (0.13) .89 1.58 (0.23) 0.11 (0.12) .36
P .83 .89 .73 – .84 .90 –
Values are mean values in nanomolars (SEM).
a
Immediately after intervention.
b
Fifteen minutes after intervention.

Table 3. Plasma concentrations of epinephrine before and after a single manipulative thrust to the upper thoracic spine
Before After a Change a Pa After b Change b Pb
Control 0.30 (0.02) 0.32 (0.03) 0.02 (0.02) .29 0.30 (0.02) 0.00 (0.02) .92
Treatment 0.29 (0.02) 0.33 (0.02) 0.03 (0.02) .11 0.30 (0.02) 0.01 (0.02) .65
P .84 .85 .68 – .91 .78 –
Values are mean values nanomolars (SEM).
a
Immediately after intervention.
b
Fifteen minutes after intervention.

parasympathetic nervous system, after a manipulative thrust Limitations

to the T3/T4 segment of patients with chronic neck pain. 41
Although the observations presented here are consistent
with previous research, this study is notable in that it uses a
novel and more direct outcome measure when compared
with other investigations of somatoautonomic reflexes from
thoracic spine manipulation and used a protocol that greatly
reduced the possibility for bias.
Any change to sympathetic outflow is expected to alter
plasma concentrations of NE and E. 31-34 The negative
results of this study suggest that either our methodology
was not sensitive enough to detect the change or that there
was no change to sympathetic outflow. Statistical evalua-
tions indicate that differences of as little as 22% between
groups could have been detected, had they occurred at
either of the sample periods examined. This was considered
a reasonable sensitivity because previous studies using
secondary measures of sympathetic activity suggest that
manual therapy is capable of inducing changes in indirect
indicators of SNS function and pain-related measures that
are approximately 20% greater than control conditions. 40
Therefore, this study provides a reliable baseline measure of
catecholamine concentrations as well as the response of
catecholamine concentrations to a thoracic manipulation in
asymptomatic subjects. These findings should inform the
design of future studies of a similar nature and aid in the
analysis of their results by providing a baseline response to
manipulation for comparison.
The present study took particular care to ensure that
extraneous factors could not influence the SNS, a strength
that provides credence to the findings. This was accom-
plished by enforcing a strict set of inclusion criteria to
ensure a homogenous subject pool and using an intravenous
line to eliminate confounds of multiple needles. However,
there are some limitations to this study. Most subjects were
not naïve to spinal manipulation, which made subject
blinding to group allocation possible only until the actual
intervention was carried out. In addition, the study did not
use any of the commonly used secondary measures of
autonomic function (eg, skin conductance or cutaneous
blood flow), which may have enabled differentiation of no
autonomic effect from no measurable change in catechol-
amine concentrations and thus a better evaluation of the
sensitivity of our methodology. Finally, this study cannot
answer questions as to whether changes might have been
detected had the manipulation been performed at other
vertebral levels (ie, cervical or lumbar spine). Spinal level is
a significant variable, as research has shown that there can
be differences in response depending on the spinal level
being stimulated. 16
Future Studies
This study used plasma concentrations of NE and E to
monitor sympathetic output and, as such, represents one of
214 Puhl and Injeyan
Sympathetic Effects of Spine Manipulation
the most direct measures of autonomic effects of thoracic
spinal manipulation in human subjects to date. In addition
to being a relatively direct measure of sympathetic activity,
measurement of catecholamine concentrations might also
provide an indirect but objective measure of pain. 42,43
Physical injury has been suggested to generate a complex
stress response that extends beyond the nervous system and
contributes to the experience of pain. 44 Future research
might thus investigate the effects of SMT on the
catecholamine levels in symptomatic subjects with spinal
dysfunction, where the basal activity of the SNS is more
likely to be altered. This approach could use catecholamine
concentrations as an objective and indirect measure of pain
and direct measure of sympathetic activity.
Future studies of a similar nature should also consider
using multiple, parallel measures of autonomic activity and
may want to consider the use of even more sensitive and
direct measures of sympathetic output. One promising
method is microneurography, the only method currently
available for directly recording efferent postganglionic
muscle sympathetic nerve activity in humans (from
peroneal or brachial nerves). 34
Finally, future investigations should consider the
application of a series of treatments, as opposed to a single
thrust manipulation. Although a recent study showed that
16 thoracic spine manipulative treatments was effective in
reducing neck pain, for patients with chronic mechanical
neck pain up to a half-year posttreatment, 45 another study
found that a single thoracic spine manipulative treatment
had no effect on neck pain. 41 If catecholamine concentra-
tions are associated with pain, then one would suspect that a
similar affect would be seen.
CONCLUSIONS
This study investigated the short-term effects of spinal
manipulation, applied to a hypomobile segment of the
upper thoracic spine (T1-T6) of asymptomatic subjects, on
the plasma concentrations of NE or E. The results of this
study indicate that a manipulative thrust to the upper
thoracic spine does not have a measurable effect on the
plasma catecholamine levels in asymptomatic subjects.
Although this study does not necessarily negate the theory
that spinal manipulation can affect the SNS, it does indicate
that catecholamine levels are not affected to a measurable
extent by a thoracic manipulation in asymptomatic subjects.
These results can thus provide a baseline measure of the
sympathetic response to spinal manipulation that will aid
in the analysis of future studies using plasma catechola-
mines as an outcome. Future studies of a similar nature
should examine the effects of SMT on the catecholamine
levels in symptomatic subjects with spinal dysfunction,
where they might also have utility as a measure of pain or
treatment efficacy.
Journal of Manipulative and Physiological Therapeutics
March/April 2012
Practical Applications
• Evidence exists to support a neurophysiological
component to manual therapies; research suggests
a somatosympathetic reflex mechanism.
• A mechanical stimulus, in the form of a high-
velocity, low-amplitude thrust, to hypomobile
segments in the upper-thoracic spine of asymp-
tomatic subjects did not affect plasma concentra-
tions of norepinephrine or epinephrine.
ACKNOWLEDGMENT
The authors acknowledge the invaluable contribution of
Larisa Shevchuk, for her assistance in the design and
implementation of the phlebotomy protocol. We also thank
Dr Christine Reinhart for her assistance in the writing and
editing of this manuscript.
FUNDING SOURCES AND POTENTIAL CONFLICTS OF INTEREST
The Research Division of the Canadian Memorial
Chiropractic College funded this study. No conflicts of
interest were reported for this study.
REFERENCES
1. Dagenais S, Gay RE, Tricco AC, Freeman MD, Mayer JM.
NASS contemporary concepts in spine care: spinal manipu-
lation therapy for acute low back pain. Spine 2010;10:918-40.
2. Vernon H, Humphreys K, Hagino C. Chronic mechanical
neck pain in adults treated by manual therapy: a systematic
review of change scores in randomized clinical trials.
J Manipulative Physiol Ther 2007;30:215-27.
3. Chaibi A, Tuchin PJ, Russell MB. Manual therapies for
migraine: a systematic review. J Headache Pain 2011;12:
127-33.
4. Bronfort G, Haas M, Evans R, Leininger B, Triano J.
Effectiveness of manual therapies: the UK evidence report.
Chiropr Osteopat 2010;18:3.
5. Leboeuf-Yde C, Pedersen EN, Bryner P, Cosman D, Hayek R,
Meeker WC, et al. Self-reported nonmusculoskeletal res-
ponses to chiropractic intervention: a multination survey.
J Manipulative Physiol Ther 2005;28:294-302.
6. Budgell B. Introduction to chiropractic theory. In: Haldeman
S, editor. Principles and practice of chiropractic. New York:
McGraw-Hill; 2005. p. 221-4.
7. Sato A, Budgell B. Somotoautonomic reflexes. In: Haldeman
S, editor. Principles and practice of chiropractic. New York:
McGraw-Hill; 2005. p. 301-14.
8. Budgell B, Hotta H, Sato A. Spinovisceral reflexes evoked
by noxious and innocuous stimulation of the lumbar spine.
J Neuromusc Sys 1995;3:122-30.
9. Budgell B, Sato A, Suzuki A, Uchida S. Responses of adrenal
function to stimulation of lumbar and thoracic interspinous
tissues in the rat. Neurosci Res 1997;28:33-40.
10. Budgell BS, Hotta H, Sato A. Reflex responses of bladder
motility after stimulation of interspinous tissues in the
anesthetized rat. J Manipulative Physiol Ther 1998;21:593-9.
Journal of Manipulative and Physiological Therapeutics
Volume 35, Number 3
11. Budgell B, Suzuki A. Inhibition of gastric motility by noxious
chemical stimulation of interspinous tissues in the rat. J Auton
Nerv Syst 2000;80:162-8.
12. Kang YM, Kenney MJ, Spratt KF, Pickar JG. Somatosympa-
thetic reflexes from the low back in the anesthetized cat.
J Neurophysiol 2003;90:2548-59.
13. Sato A, Swenson RS. Sympathetic nervous system response to
mechanical stress of the spinal column in rats. J Manipulative
Physiol Ther 1984;7:141-7.
14. Deboer KF, Schutz M, McKnight ME. Acute effects of spinal
manipulation on gastrointestinal myoelectric activity in
conscious rabbits. Man Med 1988;3:85-94.
15. Bolton P, Budgell B, Kimpton A. Influence of innocuous
cervical vertebral movement on the efferent innervation of the
adrenal gland in the rat. Auton Neurosci 2006;124:103-11.
16. Harris W, Wagnon RJ. The effects of chiropractic adjustments
on distal skin temperature. J Manipulative Physiol Ther 1987;
10:57-60.
17. Petersen N, Vicenzino B, Wright A. The effects of a cervical
mobilization technique on sympathetic outflow to the upper
limb in normal subjects. Physiother Theory Pract 1993;9:
149-56.
18. Chiu TW, Wright A. To compare the effects of different rates
of application of a cervical mobilisation technique on
sympathetic outflow to the upper limb in normal subjects.
Man Ther 1996;1:198-203.
19. Moulson A, Watson T. A preliminary investigation into the
relationship between cervical snags and sympathetic nervous
system activity in the upper limbs of an asymptomatic
population. Man Ther 2006;11:214-24.
20. Perry J, Green A. An investigation into the effects of a
unilaterally applied lumbar mobilisation technique on periph-
eral sympathetic nervous system activity in the lower limbs.
Man Ther 2008;13:492-9.
21. Sugrue N, Drysdale I. The effects of lumbar spine high
velocity low amplitude thrust (HVLAT) manipulation on
upper limb cutaneous blood supply. Int J Osteopath Med
2008;11:160.
22. McGuiness J, Vicenzino B, Wright A. Influence of a cervical
mobilization technique on respiratory and cardiovascular
function. Man Ther 1997;2:216-20.
23. Fujimoto T, Budgell B, Uchida S, Suzuki A, Meguro K.
Arterial tonometry in the measurement of the effects of
innocuous mechanical stimulation of the neck on heart rate
and blood pressure. J Auton Nerv Syst 1999;75:109-15.
24. Budgell B, Hirano F. Innocuous mechanical stimulation of
the neck and alterations in heart-rate variability in healthy
young adults. Auton Neurosci 2001;91:96-9.
25. Budgell B, Polus B. The effects of thoracic manipulation on
heart rate variability: a controlled crossover trial. J Manipu-
lative Physiol Ther 2006;29:603-10.
26. Gibbons PF, Gosling CM, Holmes M. Short-term effects of
cervical manipulation on edge light pupil cycle time: a pilot
study. J Manipulative Physiol Ther 2000;23:465.
27. Gosling C, Kinross T, Gibbons P, Holmes M. The short term
effect of atlanto-axial high velocity low amplitude manipula-
tion with cavitation on edge light pupil cycle time. Int J
Osteopath Med 2005;8:81.
28. Brennan PC, Triano JJ, McGregor M, Kokjohn K, Hondras
MA, Brennan DC. Enhanced neutrophil respiratory burst as a
Puhl and Injeyan 215
Sympathetic Effects of Spine Manipulation
biological marker for manipulation forces: duration of the
effect and association with substance P and tumor necrosis
factor. J Manipulative Physiol Ther 1992;15:83-9.
29. Teodorczyk-Injeyan JA, Injeyan HS, McGregor M, Harris
GM, Ruegg R. Enhancement of in vitro interleukin-2
production in normal subjects following a single spinal
manipulative treatment. Chiropr Osteopath 2008;16:5.
30. Teodorczyk-Injeyan JA, Injeyan HS, Ruegg R. Spinal
manipulative therapy reduces inflammatory cytokines but
not substance P production in normal subjects. J Manipulative
Physiol Ther 2006;29:14-21.
31. Yamaguchi I, Kopin IJ. Plasma catecholamine and blood
pressure responses to sympathetic stimulation in pithed rats.
Am J Physiol 1979;237:H305-10.
32. Wallin BG, Sundlof G, Eriksson BM, Dominiak P, Grobecker
H, Lindblad LE. Plasma noradrenaline correlates to sympa-
thetic muscle nerve activity in normotensive man. Acta
Physiol Scand 1981;111:69-73.
33. Oeltmann T, Carson R, Shannon JR, Ketch T, Robertson D.
Assessment of O-methylated catecholamine levels in plasma
and urine for diagnosis of autonomic disorders. Auton
Neurosci 2004;116:1-10.
34. Grassi G, Esler M. How to assess sympathetic activity in
humans. J Hypertens 1999;17:719-34.
35. Goldstein DS, McCarty R, Polinsky RJ, Kopin IJ. Relation-
ship between plasma norepinephrine and sympathetic neural
activity. Hypertension 1983;5:552-9.
36. Nansel D, Jansen R, Cremata, Dhami MS, Holley D. Effects
of cervical adjustments on lateral-flexion passive end-range
asymmetry and on blood pressure, heart rate and plasma
catecholamine levels. J Manipulative Physiol Ther 1991;14:
450-6.
37. Budgell B. Reflex effects of subluxation: the autonomic
nervous system. J Manipulative Physiol Ther 2000;23:104.
38. Himberger JR, Himberger LC. Accuracy of drawing blood
through infusing intravenous lines. Heart Lung 2001;30:
66-73.
39. Peterson DH, Bergmann TF. The spine: anatomy, biome-
chanics, assessment, and adjustive techniques. In: Peterson
DH, Bergmann TF, editors. Chiropractic technique, 2nd ed.
London: Mosby; 2007. p. 175-339.
40. Schmid A, Brunner F, Wright A, Bachmann L. Paradigm shift
in manual therapy? Evidence for a central nervous system
component in the response to passive cervical joint mobilisa-
tion. Man Ther 2008;13:387.
41. Sillevis R, Cleland J, Hellman M, Beekhuizen K. Immediate
effects of a thoracic spine thrust manipulation on the
autonomic nervous system: a randomized clinical trial.
J Man Manip Ther 2010;18:181-90.
42. Huskisson EC. Catecholamine excretion and pain. Br J Clin
Pharmacol 1974;1:80-2.
43. Huskisson EC. Measurement of pain. Lancet 1974;304:
1127-31.
44. Chapman CR, Tuckett RP, Song CW. Pain and stress in a
systems perspective: reciprocal neural, endocrine, and im-
mune interactions. J Pain 2008;9:122-45.
45. Laua HMC, Chiua TTW, Lamb TH. The effectiveness of
thoracic manipulation on patients with chronic mechanical
neck pain—a randomized controlled trial. Man Ther 2011;16:
141-7.