ArticlePDF Available

Using Functional Magnetic Resonance Imaging to Determine if Cerebral Hemodynamic Responses to Pain Change Following Thoracic Spine Thrust Manipulation in Healthy Individuals

Authors:

Abstract and Figures

Study design: Case series. Objectives: To use blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) to determine if supraspinal activation in response to noxious mechanical stimuli varies pre- and post-thrust manipulation to the thoracic spine. Background: Recent studies have demonstrated the effectiveness of thoracic thrust manipulation in reducing pain and improving function in some individuals with neck and shoulder pain. However, the mechanisms by which manipulation exerts such effects remain largely unexplained. The use of fMRI in the animal model has revealed a decrease in cortical activity in response to noxious stimuli following manual joint mobilization. Supraspinal mediation contributing to hypoalgesia in humans may be triggered following spinal manipulation. Methods: Ten healthy volunteers (5 women, 5 men) between the ages of 23 and 48 years (mean, 31.2 years) were recruited. Subjects underwent fMRI scanning while receiving noxious stimuli applied to the cuticle of the index finger at a rate of 1 Hz for periods of 15 seconds, alternating with periods of 15 seconds without stimuli, for a total duration of 5 minutes. Subjects then received a supine thrust manipulation directed to the midthoracic spine and were immediately returned to the scanner for reimaging with a second delivery of noxious stimuli. An 11-point numeric pain rating scale was administered immediately after the application of noxious stimuli, premanipulation and postmanipulation. Blood oxygenation level-dependent fMRI recorded the cerebral hemodynamic response to the painful stimuli premanipulation and postmanipulation. Results: The data indicated a significant reduction in subjects' perception of pain (P<.01), as well as a reduction in cerebral blood flow as measured by the blood oxygenation level-dependent response following manipulation to areas associated with the pain matrix (P<.05). There was a significant relationship between reduced activation in the insular cortex and decreased subjective pain ratings on the numeric pain rating scale (r = 0.59, P<.05). Conclusion: This study provides preliminary evidence that suggests that supraspinal mechanisms may be associated with thoracic thrust manipulation and hypoalgesia. However, because the study lacked a control group, the results do not allow for the discernment of the causative effects of manipulation, which may also be related to changes in levels of subjects' fear, anxiety, or expectation of successful outcomes with manipulation. Future investigations should strive to elicit more conclusive findings in the form of randomized clinical trials.
Content may be subject to copyright.
340  |  may 2013  |  volume 43  |  number 5  |  journal of orthopaedic & sports physical therapy
[
research report
]
Recently, in the physical
therapy profession con-
siderable attention has
been devoted to exam-
ining the eectiveness of
spinal manipulation in clinical
practice.9,15,16,24,65 The use of thrust ma-
nipulation applied to the thoracic spine
has been shown to result in increased
range of motion, decreased pain, and
improvements in function in subgroups
of individuals with mechanical neck and
shoulder pain.13-16,23,43,62,65 Biomechani-
cal theories to explain the eects of spi-
nal manipulation exist, yet the available
data do not suciently explain how ma-
nipulation results in short- or long-term
clinical benefits.20,34,47,56 Researchers have
attempted to identify which combination
of clinical signs, symptoms, and other
pertinent findings from the examination
may predict a favorable response to spinal
manipulation.13,43,57 A validation study of
a proposed clinical decision rule to iden-
tify patients likely to respond to thoracic
manipulation found that subjects with
mechanical neck pain improved with
STUDY DESIGN: Case series.
OBJECTIVES: To use blood oxygenation level–
dependent functional magnetic resonance imaging
(fMRI) to determine if supraspinal activation in
response to noxious mechanical stimuli varies pre
and post–thrust manipulation to the thoracic spine.
BACKGROUND: Recent studies have demon-
strated the eectiveness of thoracic thrust manipu-
lation in reducing pain and improving function in
some individuals with neck and shoulder pain. How-
ever, the mechanisms by which manipulation exerts
such eects remain largely unexplained. The use of
fMRI in the animal model has revealed a decrease
in cortical activity in response to noxious stimuli
following manual joint mobilization. Supraspinal
mediation contributing to hypoalgesia in humans
may be triggered following spinal manipulation.
METHODS: Ten healthy volunteers (5 women, 5
men) between the ages of 23 and 48 years (mean,
31.2 years) were recruited. Subjects underwent
fMRI scanning while receiving noxious stimuli
applied to the cuticle of the index finger at a rate
of 1 Hz for periods of 15 seconds, alternating with
periods of 15 seconds without stimuli, for a total
duration of 5 minutes. Subjects then received a
supine thrust manipulation directed to the mid-
thoracic spine and were immediately returned to
the scanner for reimaging with a second delivery
of noxious stimuli. An 11-point numeric pain rating
scale was administered immediately after the
application of noxious stimuli, premanipulation
and postmanipulation. Blood oxygenation level–de-
pendent fMRI recorded the cerebral hemodynamic
response to the painful stimuli premanipulation
and postmanipulation.
RESULTS: The data indicated a significant reduc-
tion in subjects’ perception of pain (P<.01), as well
as a reduction in cerebral blood flow as measured
by the blood oxygenation level–dependent response
following manipulation to areas associated with the
pain matrix (P<.05). There was a significant rela-
tionship between reduced activation in the insular
cortex and decreased subjective pain ratings on the
numeric pain rating scale (r = 0.59, P<.05).
CONCLUSION: This study provides pre-
liminary evidence that suggests that supraspinal
mechanisms may be associated with thoracic
thrust manipulation and hypoalgesia. However,
because the study lacked a control group, the
results do not allow for the discernment of the
causative eects of manipulation, which may also
be related to changes in levels of subjects’ fear,
anxiety, or expectation of successful outcomes
with manipulation. Future investigations should
strive to elicit more conclusive findings in the form
of randomized clinical trials. J Orthop Sports Phys
Ther 2013;43(5):340-348. Epub 13 March 2013.
doi:10.2519/jospt.2013.4631
KEY WORDS: fMRI, manipulation,
neuroscience, pain
1Department of Physical Therapy and Health Science, Bradley University, Peoria, IL. 2Department of Physical Therapy, Franklin Pierce University, Concord, NH. 3Department of
Physical Therapy and Human Movement Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL. 4Department of Radiology, University of Illinois College of
Medicine at Peoria, Peoria, IL. This project was supported with grant funding through the Center for Collaborative Brain Research at OSF Saint Francis Medical Center, Peoria, IL.
This study was approved by the Institutional Review Boards at the University of Illinois College of Medicine at Peoria and Nova Southeastern University. The authors certify that
they have no aliations with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript.
Address correspondence to Cheryl Sparks, Bradley University, 1501 West Bradley Avenue, Olin Hall 346, Peoria, IL 61625. E-mail: csparks@bradley.edu Copyright ©2013
Journal of Orthopaedic & Sports Physical Therapy®
CHERYL SPARKS, PT, PhD1 • JOSHUA A. CLELAND, PT, PhD2 • JAMES M. ELLIOTT, PT, PhD3
MICHAEL ZAGARDO, MD4 • WEN-CHING LIU, PhD4
Using Functional Magnetic Resonance
Imaging to Determine if Cerebral
Hemodynamic Responses to Pain
Change Following Thoracic Spine Thrust
Manipulation in Healthy Individuals
43-05 Sparks.indd 340 4/17/2013 3:55:33 PM
Journal of Orthopaedic & Sports Physical Therapy®
Downloaded from www.jospt.org at on September 15, 2017. For personal use only. No other uses without permission.
Copyright © 2013 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.
journal of orthopaedic & sports physical therapy | volume 43 | number 5 | may 2013 | 341
manipulation, regardless of their sta-
tus on the rule.16 While successful out-
comes are associated with thoracic spine
manipulation, the mechanisms associ-
ated with pain reduction remain poorly
understood.
Mechanisms associated with manip-
ulation are believed to possess varying
neurophysiological properties, including
mediation from peripheral, spinal, and
supraspinal structures.5,6,19,38,39,50,51,62,63,68
Previous studies have used functional
magnetic resonance imaging (fMRI) to
measure hemodynamic displacement to
structures within the brain over time,
serving as a local measure of cognitive,
sensory, or motor processes.12,28,35,40 With
this method, functional images are over-
laid atop higher-resolution anatomic
images, allowing inferences to be made
regarding neural activity within the
brain. Using fMRI in the animal model,
it was demonstrated that the anterior
cingulate, frontal, and somatosensory
cortices were activated in response to
noxious stimuli.38 Furthermore, de-
creased activation of these areas was
noted following manual joint mobiliza-
tion.38 Identification of the supraspinal
structures associated with manipulation
in human subjects remains a basic and
clinical research priority. Such informa-
tion may potentially aect acceptance
and use of thrust techniques by providing
a more mechanistic scientific rationale,
improving clinical reasoning for the use
of manipulation beyond basic biome-
chanics and clinical decision rules.
METHODS
Subjects
Ten healthy right-handed vol-
unteers (5 women), aged 23 to 48
years (mean SD age, 31.2 10.0
years), were recruited to participate in
the experiment. Individuals aliated
with a first professional physical thera-
pist education program were informed
of the study by word of mouth and in-
vited to participate. The subjects had no
current history of pain or orthopaedic or
systemic conditions and were of normal
body mass index (mean SD, 23.5 2.0
kg/m2). Subjects were excluded if they
were not suciently skilled in the Eng-
lish language to comply with the research
protocol or had any contraindications to
thrust manipulation or to undergoing an
MRI exam, including claustrophobia,
presence of a cardiac pacemaker, cochle-
ar implants, metal implants, implanted
hearing aids, previous injuries caused by
bullets or shrapnel, pregnancy, or think-
ing that they might be pregnant. Subjects
provided written informed consent, rec-
ognizing that they could withdraw at any
time without prejudice. The Institutional
Review Boards at the University of Illi-
nois College of Medicine at Peoria and
Nova Southeastern University approved
the study protocol.
Procedures
Following recruitment, subjects under-
went a pretest pain threshold assessment
1 day prior to their scheduled scanning
procedure. The pretest pain threshold
was determined by applying von Frey
filaments in graduated succession to the
cuticle of the index finger. The filaments
were applied for 5 seconds each, with a
20-second interstimuli interval. von Frey
monofilaments have been used in previ-
ous studies to elicit mechanical pain3,37,69
and to map networks associated with
pain in the spinal cord and brain stem
using fMRI.22 This technique’s previ-
ously reported intraobserver reliability
is fair (κ = 0.4) and its reproducibility
is fair to moderate (κ = 0.6), likely due
to the inherent variability of a manually
applied technique.64 The pain threshold
was defined as the least pressure inten-
sity at which subjects perceived pain.
The monofilament number causing the
perception of pain was recorded for use
during the scanning procedure.
The fMRI studies were performed on
10 subjects between July and September
2012. Subjects were positioned in a su-
pine hook-lying position on the scanner
table, with a bolster under the knees and
a foam pad placed transversely under
the inferior angle of the scapulae, and
another foam pad supporting the cervi-
cal spine and cervicothoracic junction
(FIGURE 1). Subjects were provided ear-
plugs, and their head was placed inside
the head coil and comfortably secured
and padded with foam to minimize head
motion (FIGURE 2). The principal investi-
gator (C.S.) applied the previously iden-
tified monofilament manually to the
cuticle of the index finger at a frequency
of 1 Hz during the fMRI scanning, at-
tempting to induce temporal summation
of pain, which is believed to be a centrally
mediated process. The stimuli were ap-
plied in a simple block paradigm of 10
consecutive cycles, each consisting of 15
seconds of stimulus and 15 seconds of
no stimulus, both premanipulation and
postmanipulation.
Following the initial application of
FIGURE 1. Foam pads were positioned transversely
under the scapulae and cervicothoracic junction. This
setup allowed the manipulation to be delivered so as
to minimize head motion.
FIGURE 2. Subject positioned to receive supine thrust
manipulation targeting the midthoracic spine.
43-05 Sparks.indd 341 4/17/2013 3:55:34 PM
Journal of Orthopaedic & Sports Physical Therapy®
Downloaded from www.jospt.org at on September 15, 2017. For personal use only. No other uses without permission.
Copyright © 2013 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.
342  |  may 2013  |  volume 43  |  number 5  |  journal of orthopaedic & sports physical therapy
[
research report
]
noxious stimuli and fMRI scan, the sub-
jects received a high-velocity, end-range,
anterior/posterior force applied through
the elbows and directed to the midtho-
racic spine on the lower thoracic spine
in cervicothoracic flexion.13,55 This tech-
nique was performed with the patient
positioned supine. Using recommended
terminology recently proposed by Mint-
ken et al,44 the therapist (C.S.) used her
manipulative hand to stabilize the infe-
rior vertebra of the targeted motion seg-
ment and used her body to push down
through the patient’s arms, performing a
high-velocity, low-amplitude thrust. The
subjects were then immediately reimaged
with fMRI while the noxious stimuli were
reapplied. The window between thrust
manipulation and initiation of scanning
did not exceed 5 minutes.
Immediately following the applica-
tion of noxious stimuli, premanipula-
tion and postmanipulation, the subjects
were asked to rate their perceived pain
on an 11-point numeric pain rating scale
(NPRS), where 0 indicated no pain and
10 indicated the worst imaginable pain.
The 11-point NPRS is considered to be a
reliable and valid tool for assessing pain
intensity.7,27,30,31 There is a strong correla-
tion and excellent agreement between a
verbal NPRS and a visual analog scale (r
= 0.93; 95% confidence interval: 0.93,
0.95), and the minimal clinically im-
portant dierence for a verbally admin-
istered NPRS for acute pain is 1.4.7 A
summary of data collection procedures
can be found in FIGURE 3.
Imaging
The fMRI data were acquired using a
3-T General Electric (GE Healthcare,
Waukesha, WI) magnetic resonance
scanner, equipped with echo planar im-
aging capabilities and a high-resolution,
8-channel head coil. High-resolution
T1-weighted structural images of each
subject’s brain were acquired with 3-D
fast spoiled gradient-echo at the start of
the study to later superimpose maps of
functional activation. A T2*-weighted
gradient echo planar imaging sequence
was used to acquire functional data pre-
manipulation and postmanipulation. T2*
diers from T2. T2* relaxation is one of
the main determinants of image contrast
with gradient echo planar imaging se-
quences. As such, it forms the basis for
many magnetic resonance applications,
including fMRI, where changes in deox-
ygenated hemoglobin can be quantified.
The sequence parameters for blood oxy-
genation level–dependent imaging were
as follows: repetition time, 3000 milli-
seconds; echo time, 30 milliseconds; flip
angle, 90°; matrix, 64 × 64; field of view,
24 cm; slices, 50; voxel size, 3.75 × 3.75 ×
3 mm3. The fMRI data were preprocessed
using FEAT (fMRI Expert Analysis Tool
Version 5.98; University of Oxford, Ox-
ford, UK), which is part of FSL (FMRIB
Software Library; www.fmrib.ox.ac.uk/
fsl). Specifically, data were corrected for
head motion using MCFLIRT (FMRIB
Linear Image Registration Tool; Univer-
sity of Oxford),29 removal of the skull and
brain extraction using the BET (Brain
Extraction Tool; University of Oxford),59
and spatial smoothing at the default of
5 mm to reduce noise without reducing
valid activation. The MELODIC program
(Multivariate Exploratory Linear Opti-
mized Decomposition into Independent
Components; University of Oxford) for
independent component analysis was run
to allow for individual visual inspection
of the data, ensuring that no unexpected
activation or artifact remained after pre-
processing.4 Following preprocessing,
hypothesis-driven, standard voxel-wise
analyses using general linear modeling
with autocorrelation correction were
used for first- and second-level analyses
and to create statistical parametric maps
of the functional data.66
Data Analysis
Within-subject 4-dimensional data
were analyzed voxel by voxel to create Z
(Gaussianized t) statistic images. These
were thresholded using clusters deter-
mined by Z>2.3 and an autocorrected
cluster significance threshold of P<.05 to
eliminate redundancy.67 Following level 1
analyses, group analyses were performed
using FLAME (FMRIB Local Analysis of
Mixed Eects; University of Oxford) to
estimate random eects and variances
between subjects. Paired t tests were per-
formed to determine the dierences in
activation between premanipulation and
postmanipulation (Z>2.3 and a cluster
significance threshold of P<.05).67 Based
on significant clusters of voxels, anatomic
regions of interest were defined using the
Harvard-Oxford cortical and subcortical
structural probabilistic atlases (Univer-
sity of Oxford; http://www.cma.mgh.
harvard.edu/).60 The subjects’ NPRS
scores were fitted to t distribution for hy-
Acquisition of anatomic images
fMRI scan taken during the delivery of
mechanical stimuli administered at a
frequency of 1 Hz for 10 consecutive
on/o cycles (5 min)
Administration of 11-point numeric
pain rating scale
Thrust manipulation to midthoracic
spine
fMRI scan taken during the delivery of
mechanical stimuli administered at a
frequency of 1 Hz for 10 consecutive
on/o cycles (5 min)
Administration of 11-point numeric
pain rating scale
FIGURE 3. Data collection procedures. Abbreviation:
fMRI, functional magnetic resonance imaging.
43-05 Sparks.indd 342 4/17/2013 3:55:35 PM
Journal of Orthopaedic & Sports Physical Therapy®
Downloaded from www.jospt.org at on September 15, 2017. For personal use only. No other uses without permission.
Copyright © 2013 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.
journal of orthopaedic & sports physical therapy | volume 43 | number 5 | may 2013 | 343
pothesis testing with paired t tests using
SPSS Statistics Version 19 (IBM Corpo-
ration, Somers, NY). Maximum Z scores
for each region of interest were used to
calculate changes in activation prema-
nipulation and postmanipulation, and
were analyzed using the Pearson prod-
uct-moment correlation coecient (r) to
determine whether a relationship existed
between the change in blood oxygenation
level–dependent response within a given
anatomic region and the subjects’ pain
ratings of stimulus intensity before and
after manipulation.
RESULTS
Pain Perception
Mean SD ratings of pain in-
tensity on the NPRS premanipu-
lation and postmanipulation were
4.5 1.1 and 2.3 1.1, respectively. The
mean dierence for subjective pain rat-
ings between premanipulation and post-
manipulation was 2.2 (95% confidence
interval: 1.8, 2.7; P<.01).
Functional Activation
Significant areas of activation (Z>2.3,
P<.05) were noted in the right and left
cerebellum, amygdala, thalami, periaque-
ductal gray (PAG), insular cortex, anterior
cingulate cortex, somatosensory cortices,
supplementary motor area, and premotor
areas during the noxious stimuli prior to
manipulation (FIGURE 4). Reduced acti-
vation in the aforementioned areas was
demonstrated following manipulation
(FIGURE 5). A 31% reduction in the voxel-
based hemodynamic response was appre-
ciated postmanipulation. There were no
areas of increased activation noted when
comparing the hemodynamic response
postmanipulation to premanipulation.
Clusters and coordinates for areas of in-
creased blood oxygenation level–depen-
dent activation in response to noxious
stimuli prior to manipulation are repre-
sented in FIGURE 6 and the TABLE. Of the
anatomical regions of interest analyzed,
only decreased activation in the insular
cortex demonstrated a significant rela-
tionship, with a reduction in subjective
reports of pain postmanipulation (r =
0.59, P = .037) (FIGURES 7 and 8).
DISCUSSION
Cortical structures, including
the somatosensory cortices (S1
and S2), insula, anterior cingulate
cortex, and the premotor and supple-
mentary motor areas, and subcortical
structures, including the thalami and
amygdala, are associated with pain per-
ception.1,11,17,41,49,53 These structures have
been defined as the pain matrix, or the
cortical and subcortical areas of the brain
most commonly activated in response to
nociceptive information.1,10,49 Additional
research has revealed that functional ar-
eas associated with the pain matrix may
also be activated in response to nonpain-
ful stimuli.2,36,46 This may be directly re-
FIGURE 4. Functional images demonstrating mean areas of cerebral blood oxygenation level–dependent activation
in response to noxious stimuli premanipulation. Statistically significant clusters of voxels meeting the threshold of
Z>2.3 and P<.05 include the right and left amygdala, parahippocampal gyrus, insula, putamen, thalamus, central
operculum, parietal operculum, anterior cingulate, precentral gyrus, postcentral gyrus, and supplementary motor
area.
FIGURE 5. Functional images demonstrating mean areas of cerebral blood oxygenation level–dependent activation
in response to noxious stimuli postmanipulation. Statistically significant clusters of voxels meeting the threshold
of Z>2.3 and P<.05 include the amygdala, insula, central operculum, parietal operculum, precentral gyrus,
postcentral gyrus, and supplementary motor area.
43-05 Sparks.indd 343 4/17/2013 3:55:36 PM
Journal of Orthopaedic & Sports Physical Therapy®
Downloaded from www.jospt.org at on September 15, 2017. For personal use only. No other uses without permission.
Copyright © 2013 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.
344  |  may 2013  |  volume 43  |  number 5  |  journal of orthopaedic & sports physical therapy
[
research report
]
lated to the amount of attention given to
the stimulus.36 It has also been proposed
that areas within the pain matrix may in-
clude an evaluative component to discern
whether the sensory input is potentially
threatening.33,45
We hypothesized that a change in
cerebral blood flow, in the form of de-
creased activation of the areas associ-
ated with pain perception, would occur
following thrust manipulation to the
thoracic spine, and a significant relation-
ship would exist between reduction in
pain perception and change in cerebral
activation. The results of this study re-
vealed significant activation in response
to noxious stimuli in the areas believed to
be associated with the pain matrix, and a
reduction in activation was noted follow-
ing thrust manipulation to the thoracic
spine. Specifically, a reduction of activa-
tion in the insular cortex was correlated
with a significant reduction in subjects’
perception of pain.
The insular cortex, as part of the lim-
bic system, is believed to be involved in
detecting saliency of sensory informa-
tion, memory, and pain perception, and
in selective transmission of this infor-
mation to other areas within the pain
matrix.33,45,48 Extensive connections exist
between the insula and other cortical ar-
eas, including the prefrontal, cingulate,
and somatosensory cortices, and subcor-
tical areas, including the amygdala and
parahippocampal gyrus.42 The insula is
also believed to play a role in regulat-
ing the sympathetic nervous system.18 As
information is processed in the insula,
rapid behaviorally relevant decisions may
be made regarding the harmfulness of the
stimulus, its intensity, and the amount of
attention it demands. For instance, this
may trigger activation in premotor and
supplementary motor areas as an indi-
vidual contemplates whether to withdraw
from the stimulus if it has been perceived
as painful. Such activation of motor areas
has been reported previously in the lit-
erature,53 and the insular cortex has been
suggested to play a role in channeling this
response.26 Additionally, the appreciation
and judgment of stimulus quality in the
insula may aect the relay of information
to the anterior cingulate cortex, somato-
sensory cortices, and amygdala, and thus
influence the subsequent responses in
these regions. Mapped projections from
the insula to the amygdala to the PAG
give rise to the notion that facilitation or
inhibition of the painful output is influ-
enced, at least in part, by swift activation
of cortical and subcortical structures and
the perception and coding of nociceptive
information.52
This study was exploratory in nature
but is the first fMRI study to potentially
identify supraspinal structures associated
with spinal manipulation and pain reduc-
tion in human subjects. The results oer
insight into the mechanisms by which
manual therapy may contribute to hypo-
algesia in appropriate patients.
Researchers have speculated that spi-
TABLE
Index of Thresholded Clusters  
of Voxels and Coordinates Representing 
the Increased Areas of Cerebral Blood 
Oxygenation Level–Dependent Activation in 
Response to Noxious Stimuli Premanipulation
When Compared to Postmanipulation
*Values are in mm.
Cluster Index Voxels Z-Maximum Z-Maximum x* Z-Maximum y* Z-Maximum z*
6: postcentral gyrus and
precentral gyrus
2314 4.4 –38 26 66
5: supramarginal gyrus, anterior
division, parietal operculum
731 3.65 58 –30 32
4: anterior cingulate gyrus,
supplementary motor area
557 3.55 –6 –4 46
3: superior parietal lobe,
postcentral gyrus
478 3.6 20 –54 66
2: cerebellum 470 3.88 6 –56 –12
1: central operculum, insular
cortex
416 3.83 44 –2 10
FIGURE 6. Functional images demonstrating mean areas of increased cerebral blood oxygenation level–dependent
activation in response to noxious stimuli prior to manipulation when compared to mean areas of blood oxygenation
level–dependent activation postmanipulation.
43-05 Sparks.indd 344 4/17/2013 3:55:37 PM
Journal of Orthopaedic & Sports Physical Therapy®
Downloaded from www.jospt.org at on September 15, 2017. For personal use only. No other uses without permission.
Copyright © 2013 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.
journal of orthopaedic & sports physical therapy | volume 43 | number 5 | may 2013 | 345
nal manipulation may modulate pain
through the activation of descending in-
hibition via activity from both the PAG
and the dorsal horn of the spinal cord.68
Postulates include the suppression of as-
cending sensory information from the
dorsal horn, patient expectation for pain
relief, or perhaps overlap between the
two. Bialosky et al5 have demonstrated re-
gion-specific decreases in pain following
spinal manipulation, based on subjects’
positive expectations for pain reduction
and hyperalgesia in conjunction with pa-
tients’ expectations of negative outcomes.
Additional evidence suggests that the be-
lievability of the intervention may con-
tribute to patient improvement.8,54 At the
spinal cord level, the reduction in pain
(temporal summation) is suggestive of
mediation via attenuation of dorsal horn
excitability.21 In this study, subjects were
only questioned about their perception of
pain during the delivery of the stimulus
and not during the o intervals. With
temporal summation, it is possible that
some subjects experienced delayed pain
during the o intervals or increasing pain
as the intervals progressed. Which of the
subjects experienced delayed sensations
or temporal summation and how these
variables might have been responsible for
diering areas of supraspinal activation
are not known.
Healthy subjects in this study report-
ed a global reduction in pain perception
and demonstrated decreased activation
in the areas associated with the pain ma-
trix following manipulation. Although
the thrust input may play a role in de-
creased cortical and subcortical activity
in response to pain, it is possible that
the subjects experienced reduced levels
of fear or anxiety, or habituation to the
stimulus over time. In addition, all sub-
jects had a connection to a professional
physical therapist education program
and noted having at least some exposure
to manipulation, either through entry-
level or continuing education or through
previous discussion of current practice
patterns. Subjects might have had a posi-
tive view of the eects of manual inter-
ventions, and this could have contributed
to an expectation of pain reduction fol-
lowing the manipulation. This has been
demonstrated clinically by Puentedura et
al,54 who showed that a patient’s precon-
ceived expectation of a positive outcome
was a variable predictive of a favorable
response to manipulation. Given the in-
volvement of the insular cortex and the
amygdala, prior experiences or expecta-
tions associated with spinal manipula-
tion might have influenced cortical and
subcortical processing of nociceptive
information and the selective transmis-
sion or gating of such information to
the PAG for descending inhibition. The
results of this study suggest that a reduc-
tion in perceived pain following spinal
manipulation may be mediated through
the complex interactions of supraspinal
structures; however, without a control
group, the precise mechanisms cannot
be determined.
Limitations
This study presents several limitations.
Because the study lacked a control
group, it is not possible to determine if
the dierence in pain perception and
hemodynamic response was simply due
to habituation to the stimulus over time.
Cortical findings associated with pain
reduction may be altered by placebo ef-
fects, in that subjects may believe ma-
nipulation will have a beneficial eect
on the pain experience. Furthermore, it
is not possible to state whether increased
activity in a given region is abnormal or
better in terms of pain perception. When
subjects are trained to respond to me-
chanical stimuli, they may accommodate
or alter their mental processes. Such ac-
commodations or alterations may reflect
changes in activity postmanipulation and
not necessarily the eects of spinal ma-
nipulation. Pain perception encompasses
both physical and emotional influences
and is inherently labile, which can have
a major influence on the consistency,
repeatability, and reproducibility of the
measurements. Researchers are unable
to definitively state that individual areas
in the brain are chiefly responsible for
specific mental functions, and the extent
to which cortical, subcortical, and spinal
cord structures are simultaneously aect-
ed by manipulation remains unknown.
Manipulation has been postulated
to have hypoalgesic eects on local and
distant areas of pain,61 and we have ex-
amined the global hypoalgesic eects of
thoracic manipulation. The reasons for
the use of thoracic spine manipulation
with noxious mechanical stimulation to
the index finger, as opposed to cervical
spine manipulation, are 2-fold: first, it
is not possible to manipulate the cervical
spine without imparting some head-neck
motion in the x, y, and z directions (in/
out and along the main magnetic field).
Thoracic manipulation can be performed
without significant movement of the head
or skull and thus allows for reliable pre-
test and posttest imaging without motion
artifacts confounding the data. Second,
manual therapy to the thoracic spine may
also induce sympathoexcitatory eects
beyond segmental distribution,32,58,62 giv-
ing rise to the notion that pain reduction
FIGURE 7. Functional images demonstrating
blood oxygenation level–dependent activation of
the insular cortex in response to noxious stimuli
premanipulation.
FIGURE 8. Functional images demonstrating
blood oxygenation level–dependent activation of
the insular cortex in response to noxious stimuli
postmanipulation.
43-05 Sparks.indd 345 4/17/2013 3:55:39 PM
Journal of Orthopaedic & Sports Physical Therapy®
Downloaded from www.jospt.org at on September 15, 2017. For personal use only. No other uses without permission.
Copyright © 2013 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.
346  |  may 2013  |  volume 43  |  number 5  |  journal of orthopaedic & sports physical therapy
[ research report ]
associated with manipulation may not be
segmentally specific.
Finally, this project aimed to estab-
lish a testing protocol and to identify
cerebral structures that may be associ-
ated with hypoalgesia following thrust
manipulation to the thoracic spine by
incorporating noxious stimuli in tandem
with functional imaging premanipula-
tion and postmanipulation. The study
design, lacking a control group, was in-
tentional and exploratory, as previous
research using fMRI to investigate su-
praspinal mechanisms associated with
manual therapy has been limited to the
animal model. This study did not aim to
investigate long-term responses, as a re-
cent systematic review has reported that
the neurophysiological eects of a single
manipulation may not exceed 5 min-
utes in duration.25 Nevertheless, despite
the limitations of the study, the results
should cultivate additional inquiry into
the theories concerning the supraspinal
mechanisms associated with manipula-
tion and how such mechanisms may con-
tribute to successful outcomes in specific
patient populations.
CONCLUSION
This study  provides  preliminary 
evidence of the activation of corti-
cal, and possibly subcortical, areas
associated with spinal manipulation. We
hypothesized that significant changes in
hemodynamic function postmanipula-
tion, in the form of reduced activation in
the areas believed to be associated with
pain perception, would be associated with
reductions in subjective reports of pain.
The findings demonstrated a reduction
in cerebral blood flow to areas associated
with the pain matrix and a significant
association between reduced activation
in the insular cortex and decreased pain
ratings on the NPRS following manipula-
tion. Though supraspinal structures may
be involved in the mediation of pain per-
ception following manipulation, definitive
causal conclusions cannot be determined
without a control group. This study pro-
vides the initial methods and data on
which to base future work in this area. t
KEY POINTS
FINDINGS: Use of fMRI has revealed
reduced activation to areas within
the healthy brain following thrust ma-
nipulation to the thoracic spine, and a
relationship may exist between reduced
activation and pain perception.
IMPLICATIONS: Pain reduction associated
with thoracic spine manipulation may
be influenced, at least in part, by cortical
and subcortical interactions within the
human brain.
CAUTION: This study was exploratory in
nature, with healthy volunteers as sub-
jects. Lacking a control group, a cause-
and-effect relationship cannot be drawn
between thoracic thrust manipulation,
pain reduction, and shifts in cerebral
blood flow. Other factors, such as re-
duced fear, anxiety, expectation for pain
relief, or habituation to the stimulus
over time, might have contributed to the
outcomes.
ACKNOWLEDGEMENTS: We would like to thank
Dr Jorge Kattah, MD of the University of Il-
linois College of Medicine at Peoria, and Ms
Kathy Carlson and Mr Richard Lathrop of
the Magnetic Resonance Imaging Department
at OSF Saint Francis Medical Center, for their
assistance with data collection. We would also
like to thank the Peoria Radiology Research
and Education Foundation and the Center for
Collaborative Brain Research at OSF Saint
Francis Medical Center in Peoria, IL for sup-
porting this project.
REFERENCES
1. Apkarian AV, Bushnell MC, Treede RD, Zubieta
JK. Human brain mechanisms of pain perception
and regulation in health and disease. Eur J Pain.
2005;9:463-484. http://dx.doi.org/10.1016/j.
ejpain.2004.11.001
2. Baliki MN, Geha PY, Apkarian AV. Parsing pain
perception between nociceptive representation
and magnitude estimation. J Neurophysiol.
2009;101:875-887. http://dx.doi.org/10.1152/
jn.91100.2008
3. Baumgärtner U, Magerl W, Klein T, Hopf HC,
Treede RD. Neurogenic hyperalgesia versus
painful hypoalgesia: two distinct mechanisms of
neuropathic pain. Pain. 2002;96:141-151.
4. Beckmann CF, Smith SM. Probabilistic indepen-
dent component analysis for functional magnetic
resonance imaging. IEEE Trans Med Imaging.
2004;23:137-152. http://dx.doi.org/10.1109/
TMI.2003.822821
5. Bialosky JE, Bishop MD, Robinson ME, Barabas
JA, George SZ. The influence of expectation on
spinal manipulation induced hypoalgesia: an
experimental study in normal subjects. BMC
Musculoskelet Disord. 2008;9:19. http://dx.doi.
org/10.1186/1471-2474-9-19
6. Bialosky JE, Bishop MD, Robinson ME, Zeppieri
G, Jr., George SZ. Spinal manipulative therapy
has an immediate eect on thermal pain sensi-
tivity in people with low back pain: a randomized
controlled trial. Phys Ther. 2009;89:1292-1303.
http://dx.doi.org/10.2522/ptj.20090058
7. Bijur PE, Latimer CT, Gallagher EJ. Validation of
a verbally administered numerical rating scale of
acute pain for use in the emergency department.
Acad Emerg Med. 2003;10:390-392.
8. Bishop MD, Bialosky JE, Cleland JA. Patient
expectations of benefit from common in-
terventions for low back pain and eects on
outcome: secondary analysis of a clinical trial of
manual therapy interventions. J Man Manip Ther.
2011;19:20-25. http://dx.doi.org/10.1179/1066981
10X12804993426929
9. Boyles RE, Ritland BM, Miracle BM, et al. The
short-term eects of thoracic spine thrust manip-
ulation on patients with shoulder impingement
syndrome. Man Ther. 2009;14:375-380. http://
dx.doi.org/10.1016/j.math.2008.05.005
10. Brooks J, Tracey I. From nociception to pain
perception: imaging the spinal and supraspinal
pathways. J Anat. 2005;207:19-33. http://dx.doi.
org/10.1111/j.1469-7580.2005.00428.x
11. Bushnell MC, Duncan GH, Hofbauer RK, Ha B,
Chen JI, Carrier B. Pain perception: is there a
role for primary somatosensory cortex? Proc Natl
Acad Sci U S A. 1999;96:7705-7709.
12. Buxton RB, Uludağ K, Dubowitz DJ, Liu
TT. Modeling the hemodynamic response
to brain activation. Neuroimage. 2004;23
suppl 1:S220-S233. http://dx.doi.org/10.1016/j.
neuroimage.2004.07.013
13. Cleland JA, Childs JD, Fritz JM, Whitman JM,
Eberhart SL. Development of a clinical prediction
rule for guiding treatment of a subgroup of pa-
tients with neck pain: use of thoracic spine ma-
nipulation, exercise, and patient education. Phys
Ther. 2007;87:9-23. http://dx.doi.org/10.2522/
ptj.20060155
14. Cleland JA, Childs JD, McRae M, Palmer JA,
Stowell T. Immediate eects of thoracic manipu-
lation in patients with neck pain: a randomized
clinical trial. Man Ther. 2005;10:127-135. http://
dx.doi.org/10.1016/j.math.2004.08.005
15. Cleland JA, Glynn P, Whitman JM, Eberhart
SL, MacDonald C, Childs JD. Short-term ef-
fects of thrust versus nonthrust mobilization/
43-05 Sparks.indd 346 4/17/2013 3:55:39 PM
Journal of Orthopaedic & Sports Physical Therapy®
Downloaded from www.jospt.org at on September 15, 2017. For personal use only. No other uses without permission.
Copyright © 2013 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.
journal of orthopaedic & sports physical therapy | volume 43 | number 5 | may 2013 | 347
manipulation directed at the thoracic spine in
patients with neck pain: a randomized clinical
trial. Phys Ther. 2007;87:431-440. http://dx.doi.
org/10.2522/ptj.20060217
16. Cleland JA, Mintken PE, Carpenter K, et al.
Examination of a clinical prediction rule to
identify patients with neck pain likely to benefit
from thoracic spine thrust manipulation and
a general cervical range of motion exercise:
multi-center randomized clinical trial. Phys Ther.
2010;90:1239-1250. http://dx.doi.org/10.2522/
ptj.20100123
17. Coghill RC, Sang CN, Maisog JM, Iadarola MJ.
Pain intensity processing within the human brain:
a bilateral, distributed mechanism. J Neuro-
physiol. 1999;82:1934-1943.
18. Critchley HD. Neural mechanisms of autonomic,
aective, and cognitive integration. J Comp Neu-
rol. 2005;493:154-166. http://dx.doi.org/10.1002/
cne.20749
19. Dishman JD, Ball KA, Burke J. First prize: central
motor excitability changes after spinal manipula-
tion: a transcranial magnetic stimulation study. J
Manipulative Physiol Ther. 2002;25:1-9.
20. Gál JM, Herzog W, Kawchuk GN, Conway PJ,
Zhang YT. Forces and relative vertebral move-
ments during SMT to unembalmed post-rigor
human cadavers: peculiarities associated with
joint cavitation. J Manipulative Physiol Ther.
1995;18:4-9.
21. George SZ, Bishop MD, Bialosky JE, Zep-
pieri G, Jr., Robinson ME. Immediate eects
of spinal manipulation on thermal pain
sensitivity: an experimental study. BMC Mus-
culoskelet Disord. 2006;7:68. http://dx.doi.
org/10.1186/1471-2474-7-68
22. Ghazni NF, Cahill CM, Stroman PW. Tactile
sensory and pain networks in the human spinal
cord and brain stem mapped by means of
functional MR imaging. AJNR Am J Neuroradiol.
2010;31:661-667. http://dx.doi.org/10.3174/ajnr.
A1909
23. González-Iglesias J, Fernández-de-las-Peñas C,
Cleland JA, Alburquerque-Sendín F, Palomeque-
del-Cerro L, Méndez-Sánchez R. Inclusion of
thoracic spine thrust manipulation into an
electro-therapy/thermal program for the man-
agement of patients with acute mechanical
neck pain: a randomized clinical trial. Man Ther.
2009;14:306-313. http://dx.doi.org/10.1016/j.
math.2008.04.006
24. González-Iglesias J, Fernández-de-las-Peñas C,
Cleland JA, del Rosario Gutiérrez-Vega M. Tho-
racic spine manipulation for the management of
patients with neck pain: a randomized clinical
trial. J Orthop Sports Phys Ther. 2009;39:20-27.
http://dx.doi.org/10.2519/jospt.2009.2914
25. Hegedus EJ, Goode A, Butler RJ, Slaven E. The
neurophysiological eects of a single session of
spinal joint mobilization: does the eect last? J
Man Manip Ther. 2011;19:143-151. http://dx.doi.
org/10.1179/2042618611Y.0000000003
26. Henderson LA, Gandevia SC, Macefield VG.
Somatotopic organization of the processing of
muscle and cutaneous pain in the left and right
insula cortex: a single-trial fMRI study. Pain.
2007;128:20-30. http://dx.doi.org/10.1016/j.
pain.2006.08.013
27. Hjermstad MJ, Fayers PM, Haugen DF, et al. Stud-
ies comparing Numerical Rating Scales, Verbal
Rating Scales, and Visual Analogue Scales for
assessment of pain intensity in adults: a system-
atic literature review. J Pain Symptom Manage.
2011;41:1073-1093. http://dx.doi.org/10.1016/j.
jpainsymman.2010.08.016
28. Huettel SA, Song AW, McCarthy G. Functional
Magnetic Resonance Imaging. 2nd ed. Sunder-
land, MA: Sinauer Associates, Inc; 2009.
29. Jenkinson M, Bannister P, Brady M, Smith S. Im-
proved optimization for the robust and accurate
linear registration and motion correction of brain
images. Neuroimage. 2002;17:825-841.
30. Jensen MP, Karoly P, Braver S. The measurement
of clinical pain intensity: a comparison of six
methods. Pain. 1986;27:117-126.
31. Jensen MP, Turner JA, Romano JM. What is the
maximum number of levels needed in pain inten-
sity measurement? Pain. 1994;58:387-392.
32. Jowsey P, Perry J. Sympathetic nervous sys-
tem eects in the hands following a grade III
postero-anterior rotatory mobilisation technique
applied to T4: a randomised, placebo-controlled
trial. Man Ther. 2010;15:248-253. http://dx.doi.
org/10.1016/j.math.2009.12.008
33. Legrain V, Iannetti GD, Plaghki L, Mouraux A.
The pain matrix reloaded: a salience detec-
tion system for the body. Prog Neurobiol.
2011;93:111-124. http://dx.doi.org/10.1016/j.
pneurobio.2010.10.005
34. Lehman GJ, McGill SM. Spinal manipulation
causes variable spine kinematic and trunk mus-
cle electromyographic responses. Clin Biomech
(Bristol, Avon). 2001;16:293-299.
35. Logothetis NK. The neural basis of the blood-
oxygen-level-dependent functional magnetic
resonance imaging signal. Philos Trans R Soc
Lond B Biol Sci. 2002;357:1003-1037. http://
dx.doi.org/10.1098/rstb.2002.1114
36. Lötsch J, Walter C, Felden L, Nöth U, Deichmann
R, Oertel BG. The human operculo-insular cortex
is pain-preferentially but not pain-exclusively ac-
tivated by trigeminal and olfactory stimuli. PLoS
One. 2012;7:e34798. http://dx.doi.org/10.1371/
journal.pone.0034798
37. Maihöfner C, Forster C, Birklein F, Neundörfer
B, Handwerker HO. Brain processing during
mechanical hyperalgesia in complex regional
pain syndrome: a functional MRI study. Pain.
2005;114:93-103. http://dx.doi.org/10.1016/j.
pain.2004.12.001
38. Malisza KL, Gregorash L, Turner A, et al. Func-
tional MRI involving painful stimulation of the
ankle and the eect of physiotherapy joint mobi-
lization. Magn Reson Imaging. 2003;21:489-496.
39. Malisza KL, Stroman PW, Turner A, Gregorash L,
Foniok T, Wright A. Functional MRI of the rat lum-
bar spinal cord involving painful stimulation and
the eect of peripheral joint mobilization. J Magn
Reson Imaging. 2003;18:152-159. http://dx.doi.
org/10.1002/jmri.10339
40. Malonek D, Dirnagl U, Lindauer U, Yamada K,
Kanno I, Grinvald A. Vascular imprints of neuro-
nal activity: relationships between the dynamics
of cortical blood flow, oxygenation, and volume
changes following sensory stimulation. Proc Natl
Acad Sci U S A. 1997;94:14826-14831.
41. Melzack R. Pain – an overview. Acta Anaesthesiol
Scand. 1999;43:880-884.
42. Menon V, Uddin LQ. Saliency, switching, attention
and control: a network model of insula function.
Brain Struct Funct. 2010;214:655-667. http://
dx.doi.org/10.1007/s00429-010-0262-0
43. Mintken PE, Cleland JA, Carpenter KJ, Bieniek
ML, Keirns M, Whitman JM. Some factors predict
successful short-term outcomes in individuals
with shoulder pain receiving cervicothoracic
manipulation: a single-arm trial. Phys Ther.
2010;90:26-42. http://dx.doi.org/10.2522/
ptj.20090095
44. Mintken PE, DeRosa C, Little T, Smith B. AAOMPT
clinical guidelines: a model for standardizing
manipulation terminology in physical therapy
practice. J Orthop Sports Phys Ther. 2008;38:A1-
A6. http://dx.doi.org/10.2519/jospt.2008.0301
45. Mouraux A, Diukova A, Lee MC, Wise RG, Iannetti
GD. A multisensory investigation of the functional
significance of the “pain matrix.Neuroimage.
2011;54:2237-2249. http://dx.doi.org/10.1016/j.
neuroimage.2010.09.084
46. Mouraux A, Iannetti GD. Nociceptive laser-
evoked brain potentials do not reflect nocicep-
tive-specific neural activity. J Neurophysiol.
2009;101:3258-3269. http://dx.doi.org/10.1152/
jn.91181.2008
47. Nansel D, Pene A, Cremata E, Carlson J. Time
course considerations for the eects of unilateral
lower cervical adjustments with respect to the
amelioration of cervical lateral-flexion passive
end-range asymmetry. J Manipulative Physiol
Ther. 1990;13:297-304.
48. Oertel BG, Preibisch C, Martin T, et al. Separating
brain processing of pain from that of stimulus
intensity. Hum Brain Mapp. 2012;33:883-894.
http://dx.doi.org/10.1002/hbm.21256
49. Peyron R, Laurent B, García-Larrea L. Functional
imaging of brain responses to pain. A review
and meta-analysis (2000). Neurophysiol Clin.
2000;30:263-288.
50. Pickar JG. Neurophysiological eects of spinal
manipulation. Spine J. 2002;2:357-371.
51. Pickar JG, Bolton PS. Spinal manipulative
therapy and somatosensory activation. J Electro-
myogr Kinesiol. 2012;22:785-794. http://dx.doi.
org/10.1016/j.jelekin.2012.01.015
52. Ploner M, Lee MC, Wiech K, Bingel U, Tracey I.
Prestimulus functional connectivity determines
pain perception in humans. Proc Natl Acad
Sci U S A. 2010;107:355-360. http://dx.doi.
org/10.1073/pnas.0906186106
53. Price DD. Psychological and neural mechanisms
of the aective dimension of pain. Science.
2000;288:1769-1772.
43-05 Sparks.indd 347 4/17/2013 3:55:40 PM
Journal of Orthopaedic & Sports Physical Therapy®
Downloaded from www.jospt.org at on September 15, 2017. For personal use only. No other uses without permission.
Copyright © 2013 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.
348  |  may 2013  |  volume 43  |  number 5  |  journal of orthopaedic & sports physical therapy
[ research report ]
MORE INFORMATION
WWW.JOSPT.ORG
@
54. Puentedura EJ, Cleland JA, Landers MR, Mintken
PE, Louw A, Fernández-de-las-Peñas C. Devel-
opment of a clinical prediction rule to identify
patients with neck pain likely to benefit from
thrust joint manipulation to the cervical spine.
J Orthop Sports Phys Ther. 2012;42:577-592.
http://dx.doi.org/10.2519/jospt.2012.4243
55. Puentedura EJ, Landers MR, Cleland JA, Mintken
PE, Huijbregts P, Fernández-de-las-Peñas C. Tho-
racic spine thrust manipulation versus cervical
spine thrust manipulation in patients with acute
neck pain: a randomized clinical trial. J Orthop
Sports Phys Ther. 2011;41:208-220. http://dx.doi.
org/10.2519/jospt.2011.3640
56. Ross JK, Bereznick DE, McGill SM. Determining
cavitation location during lumbar and thoracic
spinal manipulation: is spinal manipulation
accurate and specific? Spine (Phila Pa 1976).
2004;29:1452-1457.
57. Saavedra-Hernández M, Castro-Sánchez AM,
Fernández-de-las-Peñas C, Cleland JA, Ortega-
Santiago R, Arroyo-Morales M. Predictors for
identifying patients with mechanical neck pain
who are likely to achieve short-term success
with manipulative interventions directed at
the cervical and thoracic spine. J Manipulative
Physiol Ther. 2011;34:144-152. http://dx.doi.
org/10.1016/j.jmpt.2011.02.011
58. Sillevis R, Cleland J, Hellman M, Beekhuizen
K. Immediate eects of a thoracic spine thrust
manipulation on the autonomic nervous system:
a randomized clinical trial. J Man Manip Ther.
2010;18:181-190. http://dx.doi.org/10.1179/10669
8110X12804993427126
59. Smith SM. Fast robust automated brain extrac-
tion. Hum Brain Mapp. 2002;17:143-155. http://
dx.doi.org/10.1002/hbm.10062
60. Soldea O, Ekin A, Soldea DF, et al. Segmentation
of anatomical structures in brain MR images
using atlases in FSL – a quantitative approach.
2010 20th International Conference on Pattern
Recognition. Istanbul, Turkey: August 23-26,
2010.
61. Sparks C, Cleland J, Elliott J, Strubhar A. Su-
praspinal structures may be associated with
hypoalgesia following thrust manipulation to the
spine: a review of the literature. Phys Ther Rev.
2013;18:112-116. http://dx.doi.org/10.1179/174328
8X12Y.0000000058
62. Sueki DG, Chaconas EJ. The eect of thoracic
manipulation on shoulder pain: a regional inter-
dependence model. Phys Ther Rev. 2011;16:399-
408. http://dx.doi.org/10.1179/1743288X1
1Y.0000000045
63. Suter E, McMorland G, Herzog W. Short-term
eects of spinal manipulation on H-reflex am-
plitude in healthy and symptomatic subjects.
J Manipulative Physiol Ther. 2005;28:667-672.
http://dx.doi.org/10.1016/j.jmpt.2005.09.017
64. Tena B, Escobar B, Arguis MJ, Cantero C, Rios
J, Gomar C. Reproducibility of Electronic von
Frey and von Frey monofilaments testing. Clin J
Pain. 2012;28:318-323. http://dx.doi.org/10.1097/
AJP.0b013e31822f0092
65. Walser RF, Meserve BB, Boucher TR. The ef-
fectiveness of thoracic spine manipulation for
the management of musculoskeletal condi-
tions: a systematic review and meta-analysis of
randomized clinical trials. J Man Manip Ther.
2009;17:237-246.
66. Woolrich MW, Ripley BD, Brady M, Smith
SM. Temporal autocorrelation in univariate
linear modeling of FMRI data. Neuroimage.
2001;14:1370-1386. http://dx.doi.org/10.1006/
nimg.2001.0931
67. Worsley KJ. Statistical analysis of activation
images. In: Jezzard P, Matthews PM, Smith SM,
eds. Functional MRI: An Introduction to Methods.
Oxford, UK: Oxford University Press; 2001.
68. Wright A. Hypoalgesia post-manipulative
therapy: a review of a potential neurophysiologi-
cal mechanism. Man Ther. 1995;1:11-16. http://
dx.doi.org/10.1054/math.1995.0244
69. Ziegler EA, Magerl W, Meyer RA, Treede RD.
Secondary hyperalgesia to punctate mechanical
stimuli. Central sensitization to A-fibre nocicep-
tor input. Brain. 1999;122 pt 12:2245-2257. http://
dx.doi.org/10.1093/brain/122.12.2245
DOWNLOAD PowerPoint Slides of JOSPT Figures & Tables
JOSPT oers PowerPoint slides of figures and tables to accompany selected
articles on the Journal’s website (www.jospt.org). These slides can be
downloaded and saved and include the article title, authors, and full
citation. With each article where this feature is available, click “View Slides”
and then right click on the link and select “Save Target As”.
43-05 Sparks.indd 348 4/17/2013 3:55:41 PM
Journal of Orthopaedic & Sports Physical Therapy®
Downloaded from www.jospt.org at on September 15, 2017. For personal use only. No other uses without permission.
Copyright © 2013 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.
This article has been cited by:
1. William R. Reed, Jamie T. Cranston, Stephen M. Onifer, Joshua W. Little, Randall S. Sozio. 2017. Decreased spontaneous
activity and altered evoked nociceptive response of rat thalamic submedius neurons to lumbar vertebra thrust. Experimental
Brain Research 235:9, 2883-2892. [Crossref]
2. Charles W. Penza, Maggie E. Horn, Steven Z. George, Mark D. Bishop. 2017. Comparison of two lumbar manual therapies
on temporal summation of pain in healthy volunteers. The Journal of Pain . [Crossref]
3. Adriaan Louw, Kevin Farrell, Merrill Landers, Martin Barclay, Elise Goodman, Jordan Gillund, Sara McCaffrey, Laura
Timmerman. 2016. The effect of manual therapy and neuroplasticity education on chronic low back pain: a randomized
clinical trial. Journal of Manual & Manipulative Therapy 1-8. [Crossref]
4. Wagner Rodrigues Martins, Juscelino Castro Blasczyk, Micaele Aparecida Furlan de Oliveira, Karina Ferreira Lagôa
Gonçalves, Ana Clara Bonini-Rocha, Pierre-Michel Dugailly, Ricardo Jacó de Oliveira. 2016. Efficacy of musculoskeletal
manual approach in the treatment of temporomandibular joint disorder: A systematic review with meta-analysis. Manual
Therapy 21, 10-17. [Crossref]
5. Kenneth A. Olson. 77. [Crossref]
6. Beattie Paul F.. The Lumbar Spine: Physical Therapy Patient Management Using Current Evidence 1-46. [Abstract]
[Full Text] [PDF]
7. Kesava Kovanur Sampath, Ramakrishnan Mani, James David Cotter, Steve Tumilty. 2015. Measureable changes in the
neuro-endocrinal mechanism following spinal manipulation. Medical Hypotheses 85:6, 819-824. [Crossref]
8. Luca Buzzatti, Steven Provyn, Peter Van Roy, Erik Cattrysse. 2015. Atlanto-axial facet displacement during rotational
high-velocity low-amplitude thrust: An invitro 3D kinematic analysis. Manual Therapy 20:6, 783-789. [Crossref]
9. Mark D Bishop, Rafael Torres-Cueco, Charles W Gay, Enrique Lluch-Girbés, Jason M Beneciuk, Joel E Bialosky. 2015.
What effect can manual therapy have on a patient's pain experience?. Pain Management 5:6, 455-464. [Crossref]
10. Amy McDevitt, Jodi Young, Paul Mintken, Josh Cleland. 2015. Regional interdependence and manual therapy directed at
the thoracic spine. Journal of Manual & Manipulative Therapy 23:3, 139-146. [Crossref]
11. Jason A. Zafereo, Beth K. Deschenes. 2015. The Role of Spinal Manipulation in Modifying Central Sensitization. Journal
of Applied Biobehavioral Research 20:2, 84-99. [Crossref]
12. Paul F. Beattie, Sheri P. Silfies. 2015. Improving Long-Term Outcomes for Chronic Low Back Pain: Time for a New
Paradigm?. Journal of Orthopaedic & Sports Physical Therapy 45:4, 236-239. [Abstract] [Full Text] [PDF] [PDF Plus]
13. Stephen M. Onifer, William R. Reed, Randall S. Sozio, Cynthia R. Long. 2015. Antinociceptive Effects of Spinal
Manipulative Therapy on Nociceptive Behavior of Adult Rats during the Formalin Test. Evidence-Based Complementary
and Alternative Medicine 2015, 1-9. [Crossref]
14. Michelle E. Wormley, Jason K. Grimes, Wendy Romney, Sheng-Che Yen, Kevin K. Chui. 2015. Neurophysiological Effects
of Manual Therapy in Aging and Older Adults. Topics in Geriatric Rehabilitation 31:3, 173-179. [Crossref]
15. William R. Reed, Randall Sozio, Joel G. Pickar, Stephen M. Onifer. 2014. Effect of Spinal Manipulation Thrust Duration
on Trunk Mechanical Activation Thresholds of Nociceptive-Specific Lateral Thalamic Neurons. Journal of Manipulative
and Physiological Therapeutics 37:8, 552-560. [Crossref]
16. Charles W. Gay, Michael E. Robinson, Steven Z. George, William M. Perlstein, Mark D. Bishop. 2014. Immediate
Changes After Manual Therapy in Resting-State Functional Connectivity as Measured by Functional Magnetic Resonance
Imaging in Participants With Induced Low Back Pain. Journal of Manipulative and Physiological Therapeutics . [Crossref]
17. D. G. Sueki, K. Dunleavy, E. J. Puentedura, N. I. Spielholz, M. S. Cheng. 2014. The role of associative learning and fear
in the development of chronic pain – a comparison of chronic pain and post-traumatic stress disorder. Physical Therapy
Reviews 19:5, 352-366. [Crossref]
Journal of Orthopaedic & Sports Physical Therapy®
Downloaded from www.jospt.org at on September 15, 2017. For personal use only. No other uses without permission.
Copyright © 2013 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.
... De-identified datasets were obtained from two previously published fMRI studies that investigated changes in pain-related brain activity following thoracic SM using univariate analyses (Sparks et al., 2013;Sparks et al., 2017). The study location, equipment, imaging parameters, and stimulus (location and intensity) were the same across the studies. ...
... SM-induced changes in evoked pain-related brain activity in Studies 1 and 2 were previously explored using conventional brain mapping approaches (Sparks et al., 2013;Sparks et al., 2017). For example in Study 1 using a univariate voxelwise analysis with standard statistical thresholds, evoked-pain activity was mapped to brain areas commonly reported in experimental pain studies including the cerebellum, amygdala, thalamus, periaqueductal gray, insular cortices, anterior cingulate cortex, somatosensory cortices, and supplemental motor and premotor areas. ...
... For example in Study 1 using a univariate voxelwise analysis with standard statistical thresholds, evoked-pain activity was mapped to brain areas commonly reported in experimental pain studies including the cerebellum, amygdala, thalamus, periaqueductal gray, insular cortices, anterior cingulate cortex, somatosensory cortices, and supplemental motor and premotor areas. Post-SM activity decreased in the left postcentral and precentral gyri, right supramarginal gyrus, anterior cingulate cortex, right superior parietal lobule, right cerebellum, and right insular cortex (Sparks et al., 2013). Conventional brain mapping can reveal differences in brain activity due to physiological processes, following treatment, or between groups, aiding in our understanding of brain mechanisms and hypothesis generation. ...
Article
Full-text available
Background context: Spinal manipulation (SM) is a common treatment for neck and back pain, theorized to mechanically affect the spine leading to therapeutic mechanical changes. The link between specific mechanical effects and clinical improvement is not well supported. SM's therapeutic action may instead be partially mediated within the central nervous system. Purpose: To introduce brain-based models of pain for spinal pain and manual therapy research, characterize the distributed central mechanisms of SM, and advance the preliminary validation of brain-based models as potential clinical biomarkers of pain. Study design: Secondary analysis of two functional magnetic resonance imaging studies investigating the effect of thoracic SM on pain-related brain activity: A non-controlled, non-blinded study in healthy volunteers (Study 1, n = 10, 5 females, and mean age = 31.2 ± 10.0 years) and a randomized controlled study in participants with acute to subacute neck pain (Study 2, n = 24, 16 females, mean age = 38.0 ± 15.1 years). Methods: Functional magnetic resonance imaging was performed during noxious mechanical stimulation of the right index finger cuticle pre- and post-intervention. The effect of SM on pain-related activity was studied within brain regions defined by the Neurologic Pain Signature (NPS) that are predictive of physical pain. Results: In Study 1, evoked mechanical pain (p < 0.001) and NPS activation (p = 0.010) decreased following SM, and the changes in evoked pain and NPS activation were correlated (rRM2 = 0.418, p = 0.016). Activation within the NPS subregions of the dorsal anterior cingulate cortex (dACC, p = 0.012) and right secondary somatosensory cortex/operculum (rS2_Op, p = 0.045) also decreased following SM, and evoked pain was correlated with dACC activity (rRM2 = 0.477, p = 0.019). In Study 2, neck pain (p = 0.046) and NPS (p = 0.033) activation decreased following verum but not sham SM. Associations between evoked pain, neck pain, and NPS activation, were not significant and less clear, possibly due to inadequate power, methodological limitations, or other confounding factors. Conclusions: The findings provide preliminary evidence that SM may alter the processing of pain-related brain activity within specific pain-related brain regions and support the use of brain-based models as clinical biomarkers of pain.
... The superior temporal gyrus and middle temporal gyrus are not only auditory and speech centers but are also related to human emotions. These results were consistent with Sparks et al, 33 who induced pain stimulation in healthy individuals and performed the intervention of SMT. The results showed that the subjects' perception of pain was significantly reduced and a reduction of cerebral blood flow in the pain matrix was measured by BOLD fMRI after manipulation. ...
Article
Full-text available
Objective: To investigate the changes of regional homogeneity (Reho) values before and after spinal manipulative therapy (SMT) in patients with chronic low back pain (CLBP) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). Methods: Patients with CLBP (Group 1, n = 20) and healthy control subjects (Group 2, n = 20) were recruited. The fMRI was performed three times in Group 1 before SMT (time point 1, TP1), after the first SMT (time point 2, TP2), after the sixth SMT (time point 3, TP3), and for one time in Group 2, which received no intervention. The clinical scales were finished in Group 1 every time before fMRI was performed. The Reho values were compared among Group 1 at different time points, and between Group 1 and Group 2. The correlation between Reho values with the statistical differences and the clinical scale scores were calculated. Results: The bilateral precuneus and right mid-frontal gyrus in Group 1 had different Reho values compared with Group 2 at TP1. The Reho values were increased in the left precuneus and decreased in the left superior frontal gyrus in Group 1 at TP2 compared with TP1. The Reho values were increased in the left postcentral gyrus and decreased in the left posterior cingulate cortex and the superior frontal gyrus in Group 1 at TP3 compared with TP1. The ReHo values of the left precuneus in Group 1 at TP1 were negatively correlated with the pain degree at TP1 and TP2 (r = -0.549, -0.453; p = 0.012, 0.045). The Reho values of the middle temporal gyrus in Group 1 at TP3 were negatively correlated with the changes of clinical scale scores between TP3 and TP1 (r = 0.454, 0.559; p = 0.044, 0.01). Conclusion: Patients with CLBP showed abnormal brain function activity, which was altered after SMT. The Reho values of the left precuneus could predict the immediate analgesic effect of SMT.
... In another study in patients with subclinical pain, pain intensity and cerebral oscillations (1-32 Hz) induced by 80 s of tonic pain (hand cold-pressor test) were not modulated by SM applied on different regions of the spine (82). In functional magnetic resonance imaging (fMRI) studies, a decrease of pain-related activity was observed following a single SM, in healthy individuals (83,84) and patients with neck pain (85). Other fMRI studies also suggest that SM may reduce chronic low back pain by modulating the saliency network activity or connectivity (86,87). ...
Article
Full-text available
Musculoskeletal injuries lead to sensitization of nociceptors and primary hyperalgesia (hypersensitivity to painful stimuli). This occurs with back injuries, which are associated with acute pain and increased pain sensitivity at the site of injury. In some cases, back pain persists and leads to central sensitization and chronic pain. Thus, reducing primary hyperalgesia to prevent central sensitization may limit the transition from acute to chronic back pain. It has been shown that spinal manipulation (SM) reduces experimental and clinical pain, but the effect of SM on primary hyperalgesia and hypersensitivity to painful stimuli remains unclear. The goal of the present study was to investigate the effect of SM on pain hypersensitivity using a capsaicin-heat pain model. Laser stimulation was used to evoke heat pain and the associated brain activity, which were measured to assess their modulation by SM. Eighty healthy participants were recruited and randomly assigned to one of the four experimental groups: inert cream and no intervention; capsaicin cream and no intervention; capsaicin cream and SM at T7; capsaicin cream and placebo. Inert or capsaicin cream (1%) was applied to the T9 area. SM or placebo were performed 25 minutes after cream application. A series of laser stimuli were delivered on the area of cream application 1) before cream application, 2) after cream application but before SM or placebo, and 3) after SM or placebo. Capsaicin cream induced a significant increase in laser pain (p<0.001) and laser�evoked potential amplitude (p<0.001). However, SM did not decrease the amplification of laser pain or laser-evoked potentials by capsaicin. These results indicate that segmental SM does not reduce pain hypersensitivity and the associated pain-related brain activity in a capsaicin-heat pain model.
... A small fMRI study assessing evoked-pain in ten healthy controls pre-and post-mid-thoracic spine thrust manipulation found reductions in brain activity in regions associated with pain processing (i.e. insular cortex, thalamus, S1, S2, etc.) as well as a significant reduction in perception of pain intensity of evoked stimuli 44 . In a larger cohort of experimentally-induced low back pain subjects, MT was found to immediately alter resting-state connectivity between brain regions implicated in sensory and affective components of pain processing 16 . ...
Article
Chronic low back pain (cLBP) has been associated with changes in brain plasticity. Non-pharmacological therapies such as Manual Therapy (MT) have shown promise for relieving cLBP. However, translational neuroimaging research is needed to understand potential central mechanisms supporting MT. We investigated the effect of MT on resting-state salience network (SLN) connectivity, and whether this was associated with changes in clinical pain. Fifteen cLBP patients, and 16 matched healthy controls (HC) were scanned with resting functional Magnetic Resonance Imaging (fMRI), before and immediately after a MT intervention (cross-over design with two separate visits, pseudorandomized, grades V ‘Manipulation’ and III ‘Mobilization’ of the Maitland Joint Mobilization Grading Scale). Patients rated clinical pain (0-100) pre- and post-therapy. SLN connectivity was assessed using dual regression probabilistic independent component analysis. Both manipulation (Pre: 39.43 ± 16.5, Post: 28.43 ± 16.5) and mobilization (Pre: 38.83 ± 17.7, Post: 31.76 ± 19.4) reduced clinical back pain (p<0.05). Manipulation (but not mobilization) significantly increased SLN connectivity to thalamus and primary motor cortex. Additionally, a voxelwise regression indicated that greater MT-induced increase in SLN connectivity to the lateral prefrontal cortex was associated with greater clinical back pain reduction immediately after intervention, for both manipulation (R=-0.8) and mobilization (R=-0.54). Our results suggest that MT is successful in reducing clinical low back pain by both spinal manipulation and spinal mobilization. Furthermore, this reduction post-manipulation occurs via modulation of SLN connectivity to sensorimotor, affective, and cognitive processing regions. Perspective: Manual Therapy both reduces clinical low back pain and modulates brain activity important for the processing of pain. This modulation was shown by increased functional brain connectivity between the salience network and brain regions involved in cognitive, affective, and sensorimotor processing of pain.
... La letteratura suggerisce, inoltre, la presenza di un effetto neurofisiologico sovraspinale della manipolazione in grado di influenzare l'attività delle regioni implicate nella modulazione discendente del dolore quali la corteccia cingolata anteriore, l'amigdala, il grigio periacqueduttale e il midollo ventro-rostro mediale (24,51,52). Anche l'attività di altre aree quali la corteccia sensori-motoria S1 e S2, il cervelletto e la corteccia insulare sembrerebbero modificarsi a seguito di manipolazione spinale (53). Inoltre, si è registrata una riduzione dell'accoppiamento dell'attività corticale tra le regioni deputate alla discriminazione sensoriale e all'affettività (corteccia somatosensoriale primaria e corteccia posteriore insulare); mentre un incremento è stato osservato tra le regioni deputate all'affettività e quelle deputate alla modulazione discendente del dolore (corteccia insulare, grigio periacqueduttale) (54). ...
... Hence, considering the evidence of immediate sympatheto-excitatory responses following manipulation, Kovanur Sampath et al. [6] suggested that these SNS changes might be linked to changes in pain-modulating supraspinal mechanisms. In support of this hypothesis, the authors cited two imaging studies [92,93]. The first study conducted on neck pain patients demonstrated effects of manipulation on several supraspinal structures including the cerebellar vermis, middle temporal gyrus, visual association cortex, inferior prefrontal cortex and anterior cingulate cortex. ...
Article
Full-text available
Spinal manipulation has been an effective intervention for the management of various musculoskeletal disorders. However, the mechanisms underlying the pain modulatory effects of spinal manipulation remain elusive. Although both biomechanical and neurophysiological phenomena have been thought to play a role in the observed clinical effects of spinal manipulation, a growing number of recent studies have indicated peripheral, spinal and supraspinal mechanisms of manipulation and suggested that the improved clinical outcomes are largely of neurophysiological origin. In this article, we reviewed the relevance of various neurophysiological theories with respect to the findings of mechanistic studies that demonstrated neural responses following spinal manipulation. This article also discussed whether these neural responses are associated with the possible neurophysiological mechanisms of spinal manipulation. The body of literature reviewed herein suggested some clear neurophysiological changes following spinal manipulation, which include neural plastic changes, alteration in motor neuron excitability, increase in cortical drive and many more. However, the clinical relevance of these changes in relation to the mechanisms that underlie the effectiveness of spinal manipulation is still unclear. In addition, there were some major methodological flaws in many of the reviewed studies. Future mechanistic studies should have an appropriate study design and methodology and should plan for a long-term follow-up in order to determine the clinical significance of the neural responses evoked following spinal manipulation.
Article
Full-text available
Introduction. Although its neurophysiological effects have not been fully elucidated, current evidence suggests the clinical effectiveness of spinal manipulation. Different studies suggest that manual therapy induces changes in the autonomic nervous system (ANS). Recent studies showed that mobilization produced a sympatheticexcitatory effect. However, studies using thrust manipulation appeared to be less consistent in their results. Objectives. The main objective of this review was to evaluate whether spinal manipulation induces effects on the ANS. Another objective was to correlate the changes in the measured variables with the activation or inhibition of the sympathetic or parasympathetic nervous system and with the level of spinal manipulation. Materials and methods. We performed a literature search in the following databases: PubMed, PEDro, CINAHL and OVID, using the keywords «Manipulation, spinal» and «Autonomic Nervous System». The PEDro scale was used to assess the methodological quality. Results. Nine studies met the inclusion criteria. Six trials measured cardiovascular function indicators (blood pressure, heart rate, Heart Rate Variability). Three other trials measured the pupil reaction. In most studies, cervical or upper thoracic region was manipulated. Conclusions. Our review does not provide definitive evidence of the effects of spinal manipulation on the ANS. However, most studies observed the existence of autonomic effects by modifying parameters such as blood pressure or Heart Rate Variability after manipulation. Increased parasympathetic activation probably occurs after cervical and lumbar treatment and increased sympathetic activation after dorsal treatment.
Article
Background: Thoracic spinal manipulation can improve pain and function in individuals with shoulder pain; however, the mechanisms underlying these benefits remain unclear. Here, we evaluated the effects of thoracic spinal manipulation on muscle activity, as alteration in muscle activity is a key impairment for those with shoulder pain. We also evaluated the relationship between changes in muscle activity and clinical outcomes, to characterize the meaningful context of a change in neuromuscular drive. Methods: Participants with shoulder pain related to subacromial pain syndrome (n = 28) received thoracic manipulation of low amplitude high velocity thrusts to the lower, middle and upper thoracic spine. Electromyographic muscle activity (trapezius-upper, middle, lower; serratus anterior; deltoid; infraspinatus) and shoulder pain (11-point scale) was collected pre and post-manipulation during arm elevation, and normalized to a reference contraction. Clinical benefits were assessed using the Pennsylvania Shoulder Score (Penn) at baseline and 2-3 days post-intervention. Findings: A significant increase in muscle activity was observed during arm ascent (p = 0.002). Using backward stepwise regression analysis, a specific increase in the serratus anterior muscle activity during arm elevation explained improved Penn scores following post-manipulation (p < 0.05). Interpretation: Thoracic spinal manipulation immediately increases neuromuscular drive. In addition, increased serratus anterior muscle activity, a key muscle for scapular motion, is associated with short-term improvements in shoulder clinical outcomes.
Article
Objective The purpose of the present study was to determine the neuroendocrine response after a thoracic spinal manipulation in people with Achilles tendinopathy. Methods This was a randomized 2-sequence, 2-period crossover trial. A total of 24 participants, mean (standard deviation) age of 48 (7) years, with a diagnosis of Achilles tendinopathy (>3 mo) were randomly assigned into sequence 1 (sham intervention and then thoracic spinal manipulation) or sequence 2 (thoracic spinal manipulation and then sham intervention). The trial was conducted at a university laboratory with a washout period of 1 week. The primary outcome measure was the testosterone/cortisol (T/C) ratio (salivary samples). The secondary outcome measures included heart rate variability (measured with electrocardiography) and total oxygenation index (nmol/L) of calf muscle and Achilles tendon (measured with near-infrared spectroscopy). A 2-way mixed-model analysis of variance was performed. The statistic of interest was the condition by time interaction. Results A statistically significant condition by time interaction was found for the T/C ratio (mean difference: –0.16; confidence interval: –0.33 to 0.006; interaction: P < .05) and the total oxygenation index (mean difference: 1.35; confidence interval: –1.3 to 4.1; interaction: P < .05) of calf muscle but not for Achilles tendon (P = .6); however, no difference was found for heart rate variability (P = .5). Conclusion In people with Achilles tendinopathy, thoracic spinal manipulation resulted in immediate increase in the total oxygenation index in the calf muscle followed by an increase in the T/C ratio 6 hours post-intervention.
Article
Manual therapy initiates a cascade of neurophysiological changes in various systems including the peripheral nervous system, autonomic nervous system and the endocrine system. Of particular focus of this review was the hypothalamic-pituitary-adrenal (HPA) axis. When faced with a stressor, the HPA axis provides the frontline of defence resulting in the production of cortisol, measurement of which has been shown to be a reliable indicator of HPA axis activity. Manual therapy has been shown to influence the HPA axis. However, a functional cross-talk has been clearly demonstrated between the HPA axis and the hypothalamic-pituitary-gonadal (HPG) axis, with cortisol and testosterone inhibiting each other at all levels. This mutual inhibition may mean that multiple measures across these two systems (HPA-HPG axis) should be considered to provide an accurate representation of stress physiology. The balance between testosterone and cortisol represented as a ratio termed T/C ratio has been used for this purpose. Given the implicit role of the HPA-HPG axis in pain and inflammation and an apparent gender difference in pain perception and treatment response, T/C ratio may be of interest to osteopaths as it may enable us to capture the holistic effects of osteopathy. This review revisits the function of the HPA axis in pain and inflammation, presents a dual hormone approach in measuring the HPA axis and evaluates the implications for osteopathic practice and research.
Article
Full-text available
The thalamus is a central structure important to modulating and processing all mechanoreceptor input destined for the cortex. A large number of diverse mechanoreceptor endings are stimulated when a high velocity low amplitude thrust is delivered to the lumbar spine during spinal manipulation. The objective of this study was to determine if a lumbar thrust alters spontaneous and/or evoked nociceptive activity in medial thalamic submedius (Sm) neurons. Extracellular recordings were obtained from 94 thalamic Sm neurons in 54 urethane-anesthetized adult Wistar rats. Spontaneous activity was recorded 5 min before and after an L5 control (no thrust) and thrust (85% rat body weight; 100 ms) procedure. In a subset of responsive nociceptive-specific neurons, mean changes in noxious-evoked response (10-s pinch with clip; 795 g) at three sites (tail, contra- and ipsilateral hindpaw) were determined following an L5 thrust. Mean changes in Sm spontaneous activity (60 s bins) and evoked noxious response were compared using a mixed model repeated measures ANOVA with Bonferroni post hoc t tests and paired t tests, respectively. Compared to control, spontaneous Sm activity decreased 180–240 s following the lumbar thrust (p < 0.005). Inhibitory evoked responses were attenuated in the contralateral hindpaw following an L5 thrust compared to control (p < 0.05). No other changes in spontaneous or noxious-evoked Sm activity were found. A delayed, but prolonged suppression of spontaneous Sm activity along with changes in noxious-evoked inhibitory responses in the contralateral hindpaw following lumbar vertebra thrust suggest that thalamic submedius neurons may play a role in central pain modulation related to manual therapy intervention.
Article
Full-text available
Background: Associative learning is the theory that two stimuli can be paired to produce similar behavioral responses. In this model, a previously innocuous stimulus can become paired with a noxious stimulus to a point that this previously innocuous stimulus can result in the perception of pain. Objectives: This review discusses concepts related to neural activation and structural alterations in the presence of both chronic pain and post-traumatic stress disorder (PTSD). The role of associative learning and protective memory-based behavioral responses in the perception of pain is explored to provide a framework to inform clinical management of individuals with chronic pain and will be linked to the presence of actual or perceived threat or fear. Major Findings: Current research demonstrates that in individuals with chronic pain, cortical and subcortical processing of information shifts from normal nocioceptive processing areas to the medial prefrontal, anterior cingulate, and insular cortices, as well as the hippocampus (Hip) regions, all of which also show dysregulation, signs of gray matter atrophy, and changes in epigenetic coding. Because these regions are involved in memory, emotional processing, learning, and conditioning, it is reasonable to suggest that associative learning may be involved in the processing of both pain and PTSD. Conclusions: Clinically, rehabilitation paradigms that incorporate early intervention, positive expectation, therapeutic neuroscience education, visual imagery, movement retraining, and manual therapy all have the potential to change not only pain behavior but also the neural circuitry, epigenetic coding, and cortical morphology underlying chronic pain.
Article
Full-text available
Objective: To determine if a neuroplasticity educational explanation for a manual therapy technique will produce a different outcome compared to a traditional mechanical explanation. Methods: Sixty-two patients with chronic low back pain (CLBP) were recruited for the study. Following consent, demographic data were obtained as well as pain ratings for low back pain (LBP) and leg pain (Numeric Pain Rating Scale), disability (Oswestry Disability Index), fear-avoidance (Fear-Avoidance-Beliefs Questionnaire), forward flexion (fingertips-to-floor), and straight leg raise (SLR) (inclinometer). Patients were then randomly allocated to receive one of two explanations (neuroplasticity or mechanical), a manual therapy technique to their lumbar spine, followed by post-intervention measurements of LBP, leg pain, forward flexion, and SLR. Results: Sixty-two patients (female 35 [56.5%]), with a mean age of 60.1 years and mean duration of 9.26 years of CLBP participated in the study. There were no statistically significant interactions for LBP (p = .325), leg pain (p = .172), and trunk flexion (p = .818) between the groups, but SLR showed a significant difference in favor of the neuroplasticity explanation (p = .041). Additionally, the neuroplasticity group were 7.2 times (95% confidence interval = 1.8-28.6) more likely to improve beyond the MDC on the SLR than participants in the mechanical group. Discussion: The results of this study show that a neuroplasticity explanation, compared to a traditional biomechanical explanation, resulted in a measureable difference in SLR in patients with CLBP when receiving manual therapy. Future studies need to explore if the increase in SLR correlated to changes in cortical maps of the low back.
Article
Full-text available
Optimizing pain relief resulting from spinal manipulative therapies, including low velocity variable amplitude spinal manipulation (LVVA-SM), requires determining their mechanisms. Pain models that incorporate simulated spinal manipulative therapy treatments are needed for these studies. The antinociceptive effects of a single LVVA-SM treatment on rat nociceptive behavior during the commonly used formalin test were investigated. Dilute formalin was injected subcutaneously into a plantar hindpaw. Licking behavior was video-recorded for 5 minutes. Ten minutes of LVVA-SM at 20° flexion was administered with a custom-made device at the lumbar (L5) vertebra of isoflurane-anesthetized experimental rats ( n = 12 ) beginning 10 minutes after formalin injection. Hindpaw licking was video-recorded for 60 minutes beginning 5 minutes after LVVA-SM. Control rats ( n = 12 ) underwent the same methods except for LVVA-SM. The mean times spent licking the formalin-injected hindpaw of both groups 1–5 minutes after injection were not different. The mean licking time during the first 20 minutes post-LVVA-SM of experimental rats was significantly less than that of control rats ( P < 0.001 ). The mean licking times of both groups during the second and third 20 minutes post-LVVA-SM were not different. Administration of LVVA-SM had a short-term, remote antinociceptive effect similar to clinical findings. Therefore, mechanistic investigations using this experimental approach are warranted.
Article
Full-text available
Manual therapy (MT) is a passive, skilled movement applied by clinicians that directly or indirectly targets a variety of anatomical structures or systems, which is utilized with the intent to create beneficial changes in some aspect of the patient pain experience. Collectively, the process of MT is grounded on clinical reasoning to enhance patient management for musculoskeletal pain by influencing factors from a multidimensional perspective that have potential to positively impact clinical outcomes. The influence of biomechanical, neurophysiological, psychological and nonspecific patient factors as treatment mediators and/or moderators provides additional information related to the process and potential mechanisms by which MT may be effective. As healthcare delivery advances toward personalized approaches there is a crucial need to advance our understanding of the underlying mechanisms associated with MT effectiveness.
Article
Full-text available
Thoracic spine manipulation is commonly used by physical therapists for the management of patients with upper quarter pain syndromes. The theoretical construct for using thoracic manipulation for upper quarter conditions is a mainstay of a regional interdependence (RI) approach. The RI concept is likely much more complex and is perhaps driven by a neurophysiological response including those related to peripheral, spinal cord and supraspinal mechanisms. Recent evidence suggests that thoracic spine manipulation results in neurophysiological changes, which may lead to improved pain and outcomes in individuals with musculoskeletal disorders. The intent of this narrative review is to describe the research supporting the RI concept and its application to the treatment of individuals with neck and/or shoulder pain. Treatment utilizing both thrust and non-thrust thoracic manipulation has been shown to result in improvements in pain, range of motion and disability in patients with upper quarter conditions. Research has yet to determine optimal dosage, techniques or patient populations to which the RI approach should be applied; however, emerging evidence supporting a neurophysiological effect for thoracic spine manipulation may negate the need to fully answer this question. Certainly, there is a need for further research examining both the clinical efficacy and effectiveness of manual therapy interventions utilized in the RI model as well as the neurophysiological effects resulting from this intervention.
Article
Primary outcome: There were no differences in the immediate change in TSP measured at the foot between SMT and MOB, however both treatments were superior to the REST condition. Subgroup analysis: The response to a standard TSP protocol was best characterized by three clusters: 52% no change (n = 48, 52%); facilitatory response (n = 24, 26%), and inhibitory response (n = 20, 22%). There was a significant time by treatment group by cluster interaction for TSP measured at the foot. The inhibitory cluster showed the greatest attenuation of TSP following SMT and MOB when compared to REST. These data suggest lumbar manual therapies of different velocities produce a similar localized attenuation of TSP, compared to no treatment. Attenuation of localized pain facilitatory processes by manual therapies was greatest in pain-free individuals who demonstrate an inhibitory TSP response. Perspective: The attenuation of pain facilitatory measures may serve an important underlying role in the therapeutic response to manual therapies. Identifying patients in pain who still have an inhibitory capacity (i.e. an inhibitory response subgroup) may be useful clinically in identifying the elusive "manual therapy" responder.
Article
Musculoskeletal conditions are a common occurrence among older adults, often requiring physical therapy services. Physical therapy interventions, including manual therapy, have demonstrated positive outcomes in older adults. Decades of clinical research in the field of orthopedic physical therapy indicates the positive outcomes of this approach; however, the underlying basis regarding the efficacy of manual therapy interventions remains unknown. The purpose of this article is to review the evidence surrounding the neurophysiological effects of manual therapy, specifically mobilization and manipulation, in aging and older adults (ie, those ≥ 50 years of age).