Group Title: BMC Musculoskeletal Disorders
Title: Immediate effects of spinal manipulation on thermal pain sensitivity : an experimental study
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Title: Immediate effects of spinal manipulation on thermal pain sensitivity : an experimental study
Physical Description: Book
Language: English
Creator: George, Steven Z.
Bishop, Mark D.
Bialosky, Joel E.
Zeppieri, Giorgio
Robinson, Michael E.
Publisher: BMC Musculoskeletal Disorders
Publication Date: 2006
 Notes
Abstract: BACKGROUND:The underlying causes of spinal manipulation hypoalgesia are largely unknown. The beneficial clinical effects were originally theorized to be due to biomechanical changes, but recent research has suggested spinal manipulation may have a direct neurophysiological effect on pain perception through dorsal horn inhibition. This study added to this literature by investigating whether spinal manipulation hypoalgesia was: a) local to anatomical areas innervated by the lumbar spine; b) correlated with psychological variables; c) greater than hypoalgesia from physical activity; and d) different for A-delta and C-fiber mediated pain perception.METHODS:Asymptomatic subjects (n = 60) completed baseline psychological questionnaires and underwent thermal quantitative sensory testing for A-delta and C-fiber mediated pain perception. Subjects were then randomized to ride a stationary bicycle, perform lumbar extension exercise, or receive spinal manipulation. Quantitative sensory testing was repeated 5 minutes after the intervention period. Data were analyzed with repeated measures ANOVA and post-hoc testing was performed with Bonferroni correction, as appropriate.RESULTS:Subjects in the three intervention groups did not differ on baseline characteristics. Hypoalgesia from spinal manipulation was observed in lumbar innervated areas, but not control (cervical innervated) areas. Hypoalgesic response was not strongly correlated with psychological variables. Spinal manipulation hypoalgesia for A-delta fiber mediated pain perception did not differ from stationary bicycle and lumbar extension (p > 0.05). Spinal manipulation hypoalgesia for C-fiber mediated pain perception was greater than stationary bicycle riding (p = 0.040), but not for lumbar extension (p = 0.105).CONCLUSION:Local dorsal horn mediated inhibition of C-fiber input is a potential hypoalgesic mechanism of spinal manipulation for asymptomatic subjects, but further study is required to replicate this finding in subjects with low back pain.
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Research article

Immediate effects of spinal manipulation on thermal pain
sensitivity: an experimental study
Steven Z George* 1, Mark D Bishop2, Joel E Bialosky3, Giorgio Zeppieri Jr4 and
Michael E Robinson5


Address: 'Department of Physical Therapy, Brooks Center for Rehabilitation Studies, PO Box 100154, University of Florida, Gainesville, FL, 32610-
0154, USA, 2Department of Physical Therapy, PO Box 100154, University of Florida Gainesville, FL 32610-0154, USA, 3Department of Physical
Therapy, PO Box 100154, University of Florida Gainesville, FL 32610-0154, USA, 4SHANDs and the University of Florida, PO Box 100154,
Gainesville, FL 32610-0154, USA and 5Department of Clinical and Health Psychology, Center for Pain Research and Behavioral Health, University
of Florida, Gainesville, FL 32610-0165, USA
Email: Steven Z George* sgeorge@phhp.ufl.edu; Mark D Bishop mbishop@phhp.ufl.edu; Joel E Bialosky jbialosky@phhp.ufl.edu;
Giorgio Zeppieri zeppig@shands.ufl.edu; Michael E Robinson merobin@ufl.edu
* Corresponding author


Published: 15 August 2006
BMC Musculoskeletal Disorders 2006, 7:68 doi: 10.1 186/1471-2474-7-68


Received: 26 April 2006
Accepted: 15 August 2006


This article is available from: http://www.biomedcentral.com/1471-2474/7/68
2006 George et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Abstract
Background: The underlying causes of spinal manipulation hypoalgesia are largely unknown. The
beneficial clinical effects were originally theorized to be due to biomechanical changes, but recent
research has suggested spinal manipulation may have a direct neurophysiological effect on pain
perception through dorsal horn inhibition. This study added to this literature by investigating
whether spinal manipulation hypoalgesia was: a) local to anatomical areas innervated by the lumbar
spine; b) correlated with psychological variables; c) greater than hypoalgesia from physical activity;
and d) different for A-delta and C-fiber mediated pain perception.
Methods: Asymptomatic subjects (n = 60) completed baseline psychological questionnaires and
underwent thermal quantitative sensory testing for A-delta and C-fiber mediated pain perception.
Subjects were then randomized to ride a stationary bicycle, perform lumbar extension exercise, or
receive spinal manipulation. Quantitative sensory testing was repeated 5 minutes after the
intervention period. Data were analyzed with repeated measures ANOVA and post-hoc testing
was performed with Bonferroni correction, as appropriate.
Results: Subjects in the three intervention groups did not differ on baseline characteristics.
Hypoalgesia from spinal manipulation was observed in lumbar innervated areas, but not control
(cervical innervated) areas. Hypoalgesic response was not strongly correlated with psychological
variables. Spinal manipulation hypoalgesia for A-delta fiber mediated pain perception did not differ
from stationary bicycle and lumbar extension (p > 0.05). Spinal manipulation hypoalgesia for C-fiber
mediated pain perception was greater than stationary bicycle riding (p = 0.040), but not for lumbar
extension (p = 0.105).
Conclusion: Local dorsal horn mediated inhibition of C-fiber input is a potential hypoalgesic
mechanism of spinal manipulation for asymptomatic subjects, but further study is required to
replicate this finding in subjects with low back pain.


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Background
There is considerable evidence suggesting that spinal
manipulative therapy (SMT) is an effective treatment for
subgroups of patients with low back pain (LBP) [1-4]. Fur-
thermore, a clinical prediction rule indicative of optimal
treatment outcomes from SMT has been proposed [5] and
validated [6]. While the clinical literature provides strong
support for the use of SMT for certain patients, its under-
lying effects and mechanisms are not widely understood.

SMT is frequently theorized to correct mechanical lesions,
such as "subluxation" or "segmental dysfunction", despite
the lack of empirical support for such theories [7,8]. SMT
does appear to have demonstrable mechanical (i.e. peak
forces and displacement) effects on spinal segments [9-
17]. However, there is skepticism as to whether therapeu-
tic benefits of SMT can be solely attributed to these effects.
First, peak forces generated from SMT vary greatly by prac-
titioner, suggesting this factor is not related to clinical
improvement [18,19]. Second, lasting positional changes
following SMT have not been observed [20], suggesting
this factor is also not related to clinical improvement.

Neurophysiological processes have also been used to
explain the underlying effect of SMT [13,21-23]. Specific
to the purposes of this study, SMT has been theorized to
affect spinal joint and muscle spindle mechanoreceptors,
activating low (A-beta) and high (A-delta, C) threshold
afferents [7]. This afferent input converges on the spinal
cord with the potential to inhibit dorsal horn cells
involved with transmission or amplification of nocicep-
tive input. In this scenario, SMT's underlying effect would
be as a "counter-irritant" stimulus to peripheral nocicep-
tive input received by dorsal horn cells [7].

If these neurophysiological processes occurred, SMT
would have a measurable hypoalgesic effect on pain per-
ception. This topic was reviewed by Vernon [24], with
SMT hypoalgesia observed by decreased cutaneous recep-
tive field from pin-prick [25], tolerance from electrical
current [26], and mechanical pressure [27], Collectively,
these results demonstrate SMT's potential for dorsal horn
mediated pain inhibition.

There are, however, several important, unresolved issues
regarding SMT hypoalgesia. The previously cited studies
investigated hypoalgesia in anatomical areas with the
same or overlapping dermatomes as those affected by
SMT [25-27], For example, assessing hypoalgesic response
to cervical manipulation only in anatomical areas inner-
vated by cervical nerve roots [27]. As a result, these studies
were unable to determine if the observed hypoalgesia was
a large, general effect or a specific effect local to the spinal
levels involved with the manipulation [24]. Previous stud-
ies utilized pain induction protocols assessing general


peripheral pain perception, instead of distinguishing
SMT's separate effect on A-delta and C-fiber mediated
pain perception [28]. Last, the previously cited literature
included comparisons with a true control group [26],
detuned short-wave therapy [251, and oscillatory mobili-
zation [27]. Subjects performing general physical activity
or specific back exercises are clinically relevant compari-
son groups missing from the current SMT hypoalgesia lit-
erature.

Consequently, the present study investigated the immedi-
ate hypoalgesic effects of lumbar SMT on thermal pain
sensitivity in asymptomatic subjects. We selected thermal
stimuli for pain induction because unlike other experi-
mental pain methods, it offered the sensitivity to test dif-
ferent anatomical areas and separate testing of A-delta
fiber and C-fiber mediated pain perception [28-30]. Our
first purpose was to determine if lumbar SMT hypoalgesia
was a locally observed phenomenon by demonstrating a)
hypoalgesia in lumbar innervated sites, but not in the con-
trol (cervical innervated) sites and b) hypoalgesia had a
low correlation with relevant pain-related cognitions. Our
second purpose was to determine if lumbar SMT
hypoalgesic effects were a) greater than hypoalgesia from
physical activity and b) different for A-delta fiber or C-
fiber mediated pain responses.

Methods
Subjects
This sample was comprised of undergraduate and gradu-
ate students who responded to study advertisements
placed in health science classrooms of a large research uni-
versity. Subjects read and signed a consent form that had
been approved by University's Institutional Review Board
before participating in any study-related procedures. Sub-
jects were verbally screened for history of LBP and current
use of pain relievers. Subjects not currently experiencing
LBP and not using pain relievers were included in this
study.

Procedure
Demographic information, previous pain experience, psy-
chological questionnaires, and thermal pain sensitivity
measures were collected before intervention was ran-
domly assigned. Each of the randomly assigned interven-
tions was applied for a standard 5-minute period to
minimize variation in hypoalgesic effect due to differ-
ences related to re-assessment time and treatment dosage.
The thermal pain sensitivity measures were collected
again 5 minutes after intervention was administered. Our
rationale for only measuring immediate effects was two-
fold. First, this was a preliminary study and we wanted to
confirm that we could detect hypoalgesic effects on ther-
mal sensitivity under ideal circumstances. Second, this
study involved asymptomatic subjects and we did not


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expect them to have a long-term response to these inter-
ventions because of a lack of appropriate disease process.

Measures
Psychological questionnaires
We selected psychological variables with previously
reported influence on quantitative sensory testing [31-
34].

The Fear of Pain Questionnaire (FPQ-III) uses a 30-item, 5-
point rating scale to measure fear about specific situations
that would normally produce pain [35]. The FPQ-III is a
commonly used and well-validated instrument that is
appropriate for use in non-clinical and clinical popula-
tions [35-37].

The Coping Strategies Questionnaire (CSQ) uses a 27-item,
7-point rating scale to measures the frequency of use for
common pain coping strategies [381. The CSQ is com-
monly used in pain studies and is appropriate for use in
non-clinical and clinical populations. We utilized the cat-
astrophizing sub scale that measures helplessness and pes-
simistic cognitions related to pain perception. The validity
of this particular subscale has been supported [38-41] and
the currently recommended scoring system was used in
this study [401.

The State-Trait Anxiety Questionnaire (STAI) uses a 40-item,
4-point rating scale to assess dispositional (trait) and situ-
ational (state) anxiety symptoms [42]. The STAI is com-
monly used to assess anxiety and is appropriate for use in
non-clinical and clinical populations. We reported the
state portion of the STAI as this construct better matched
the purposes of this study.

The Anxiety Sensitivity Index (ASI) uses a 16-item, 4-point
rating scale to assess anxiety sensitivity, which is the per-
ception of whether experiencing symptoms of anxiety
causes harm. The ASI is commonly used in pain studies
and is appropriate for use in non-clinical and clinical pop-
ulations. The ASI has been validated in community sam-
ples [43] and has demonstrated factor invariance across
different sex and age groups [44].

Thermal pain sensitivity
Subjects underwent quantitative sensory testing as per
previously established protocols involving thermal stim-
uli [29,30,45,46]. We selected this protocol because
unlike other methods of experimental pain induction
thermal stimuli is sensitive to A-delta fiber and C-fiber
mediated pain perception. We used a protocol with
parameters that parallel those from basic studies [28] and
was successful in detecting hypoalgesic response for
healthy controls taking fentanyl [29].


Thermal stimuli were delivered via contact thermode and
a computer-controlled Medoc Neurosensory Analyzer
(TSA-2001, Ramat Yishai, Israel) with a hand-held, pel-
tier-element-based stimulator. In our pilot testing of this
protocol (n = 10), we included a stimulation site involv-
ing lumbar paraspinal musculature. However, subjects
were unable to distinguish between A-delta fiber and C-
fiber mediated pain perception, in comparison to testing
in the extremities. We attributed this difference to the rel-
atively short distance the thermal stimuli had to travel to
the dorsal horn from the lumbar musculature. This short
distance did not allow subjects to differentiate input
based on fiber type. Therefore, we limited pain perception
testing to extremity areas innervated by lumbar and cervi-
cal dermatomes in the present study.

Stimuli were applied to the subjects' non-dominant sides
and stimulus sites included areas innervated by lumbar
dermatomes (the plantar surface of the foot and the pos-
terior calf). Control sites included areas innervated by cer-
vical dermatomes (the volar surface of the hand and
forearm). Order of stimulation sites was counter-balanced
to prevent ordering effects and exact stimulation sites were
varied to prevent carryover effects due to spatial summa-
tion, local sensitization, or suppression of nociceptors.
The interval between stimuli was at least 60 seconds to
avoid carryover effects for the preceding thermal stimulus.
Subject response to thermal stimuli was determined with
a numerical rating scale (NRS) for evoked pain intensity.
The NRS for evoked pain intensity ranged from "0" (No
pain) to "100" (Worst pain intensity imaginable).

Subjects were familiarized to the thermal stimuli with a
practice session. In the practice session, a continuous heat
stimulus was delivered to the subjects' dominant arm. The
stimulus started at 35 C and was increased at a rate of
0.5C with subjects terminating the stimulus when the
temperature reached pain threshold. This was repeated
three times and the average threshold was calculated. In
addition to familiarizing the subjects to thermal stimuli,
the pain threshold data allowed us to investigate if the
intervention groups were confounded by general pain
sensitivity. We then assessed specific components of ther-
mal pain sensitivity from previously reported protocols
[29,30,45].

First pain response
Heat stimuli of 3 seconds duration were applied to the
subjects' skin. The temperature rose rapidly (10C/sec)
from a baseline of 35 C to a randomly determined peak
of 45, 47, 49, or 50C. The research assistant recorded
NRS ratings of pain intensity. Subjects were asked to rate
their "first" pain intensity felt. These ratings are believed
to be primarily mediated by input from A-delta fibers
[28,291.


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Temporal summation
A train of 10 consecutive heat pulses of <1 second dura-
tion at an inter-stimulus interval of .33 Hz was delivered
to the subjects. A frequency of .33 Hz was selected to
ensure the development of temporal summation [28].
The temperature of the heat pulses rapidly fluctuated
(100C/sec) from a low of 350C to a peak of 470C. Tem-
perature levels were monitored by a contactor-contained
thermistor, and returned to a preset baseline of 35 C by
active cooling. The research assistant recorded NRS ratings
of pain intensity. Subjects were asked to rate their delayed
(second) pain intensity associated with the first, third, and
fifth heat pulses. These ratings are believed to be primarily
mediated by C-fiber input [28,29].

Intervention
Subjects were given a standard instructional set that each
intervention was commonly used as part of LBP treat-
ment. Subjects were then randomly assigned to receive
one of the following interventions. All interventions were
performed under the supervision of research staff to
ensure compliance with the described parameters.

Stationary bicycle. Subjects rode a stationary bicycle for 5
minutes at 60-70 rpm and 1 KP. This intervention served
as a non-specific, active comparison group with which to
compare specific active and passive interventions used to
treat spine pain. Our rationale for not including a control
group is that we wanted the comparison group for this
study to account for non-specific effects related to per-
forming general physical activity.

Lumbar extension exercise subjects performed a prone
extension exercise previously described in the literature
for treatment of LBP [47,48]. This exercise involves the
patient lying flat in a prone position. Then, the patient
used his/her arms to press his/her chest of the treatment
table, and extending the lumbar spine. Subjects were
given verbal cues to maintain their hips in contact with
the treatment table to prevent substitution from other
anatomical areas. Several studies support the effectiveness
of this exercise and no adverse events have been reported
[49-53]. Subjects performed 3 sets of 15 repetitions within
a 5-minute period.

SMT. Subjects received a lumbar SMT previously described
in the literature for treatment of LBP (Figure 1) [47]. This
SMT technique is performed with the patient supine, and
the researcher standing on the opposite side of the table.
The researcher passively side bent the patient toward the
side to be manipulated and asked the subject to interlock
hands behind his/her head. The researcher then passively
rotated the subject away from the side to be manipulated
and delivered a posterior and inferior thrust to the oppo-
site ASIS. Several randomized trials support the efficacy of


Figure I
Spinal manipulation technique utilized in this
study(5;47;54-56). (Reprinted with permission of the
American Physical Therapy Association from Cibulka MT.
The treatment of the sacroiliac joint component to low back
pain: a case report. Phys Ther. 1992;72:917-922.)


this specific technique and no adverse events have been
reported [5,54-56]. The SMT was performed four times
within a 5-minute period, alternating thrusts between
right and left ASIS's. Specifically, the researcher applying
the manipulation was trained to pace the repositioning
process to take 1 minute, allowing 10-15 seconds to per-
form the thrust.

Data analysis
All data analyses were performed using SPSS for Windows
(SPSS Inc, 233 S. Wacker Drive, 11th floor, Chicago, Illi-
nois 60606), Version 13.0 at a Type I error rate of 0.05.
Descriptive statistics were generated for the demographic,
psychological, and pain threshold measures. Randomiza-
tion effect was investigated by comparing treatment
groups with one-way ANOVA. Any observed group differ-
ences were considered as covariates in the subsequent
analyses.

Our purposes were investigated by testing for group x
time interactions for either first pain response or temporal
summation in the lumbar and cervical innervated testing
sites. First pain response for 47 and 49 C was tested with
repeated measures ANOVA. Data for 45 and 500C were
not presented because these data represented sub-thresh-
old (i.e. floor effect for hypoalgesia) and tolerance (i.e.
ceiling effect for hypoalgesia) values for a majority of
patients, respectively. Treatment group [3] and pre and
post NRS first pain ratings [21 were the model factors.
Temporal summation was tested with repeated measures
ANOVA, with treatment group [31 and pre and post NRS
temporal summation ratings [2] as the model factors. The
3 primary analyses involving repeated measures ANOVA


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models were performed without correction of the Type I
error rate. This strategy was selected because this was a
preliminary study and we wanted to utilize a liberal defi-
nition of statistical significance to avoid potential misin-
terpretation of the data. However, any post-hoc testing
was performed with Bonferroni correction of the 0.05
Type I error rate. We also calculated Pearson product cor-
relations between psychological variables, pain threshold
measures, and SMT hypoalgesia.

Results
The 3 treatment groups did not significantly differ on the
demographic, previous pain experience, psychological,
and pain threshold measures (Table 1). There were no sig-
nificant group x time interactions for first pain hypoalge-
sia in the cervical innervated sites at either 47C (F1,57 =
0.4, partial r2 = 0.02, p = 0.645) or at 490C (F1,57 = 0.3,
partial r12 = 0.01, p = 0.720). In addition, there was no sig-
nificant hypoalgesia (i.e. treatment effect) for the cervical
innervated sites at either temperature (Table 2). Similarly,
there was no significant group x time interaction for tem-
poral summation hypoalgesia in the cervical innervated
sites (F1,57= 0.5, partial r2= 0.02, p = 0.620) and there was
no general temporal summation hypoalgesic effect in the
cervical innervated sites (F1,57 = 0.7, p = 0.405).

There were no significant group x time interactions for
first pain response hypoalgesia in lumbar innervated sites
at either 47C (F1,57= 2.4, partial r2 = 0.08, p = 0.101) or
at 49 oC (F1,57= 1.3, partial r2 = 0.05, p = 0.268). However,
there was a significant hypoalgesia (i.e. treatment effect)
on the lumbar innervated sites at both temperatures. All
interventions were associated with first pain hypoalgesia,
but only SMT had a consistent association (Table 2).
There was a significant group x time interaction for tem-
poral summation hypoalgesia in the lumbar innervated


sites (F1,57 = 3.7, partial r12 = 0.12, p = 0.030). Temporal
summation hypoalgesic responses are included in Figure
2 to allow descriptive comparisons of the cervical and
lumbar innervated responses. Post-hoc testing revealed
that SMT had a larger hypoalgesic effect in the lumbar
innervated sites than stationary bicycle (p = 0.040), but
similar as lumbar extension exercise (p = 0.105).

The Pearson correlations among the psychological, pain
threshold, and SMT hypoalgesic response variables were
generally low, ranging from -0.31 to 0.25, and none
reached statistical significance (Table 3).

Discussion
This study investigated the immediate hypoalgesic effect
of lumbar SMT on thermal pain sensitivity in asympto-
matic subjects. The first purpose was to investigate
whether SMT hypoalgesia was a local phenomenon. This
purpose adds to the existing literature because previous
studies have demonstrated SMT hypoalgesia by testing
anatomical sites primarily affected by the manipulative
technique [25-27]. As a result, there is a question whether
SMT hypoalgesia was the result of a general or local nerv-
ous system response [24]. Our results support SMT
hypoalgesia as primarily a local phenomenon. First, there
were no hypoalgesic effects observed in cervical inner-
vated sites, but there were hypoalgesic effects observed in
the lumbar innervated sites. The implication of this find-
ing is that the dorsal horn inhibition from SMT did not
have a wide-ranging effect on peripheral input received
from lumbar and cervical dermatomes. Second, there
were no statistically significant or large correlations
between pain-related cognitions, pain threshold, and the
SMT hypoalgesic response. For example, the largest corre-
lation was with state anxiety (r = -0.31), suggesting this
cognition accounted for only 9.6% variance in the


Table I: Descriptive statistics for sample


Variable

Age (years)
Sex (# female, %)
Worst pain experienced (NRS)
Fear of pain (FPQ)
Pain catastrophizing (CSQ-R)
Anxiety (STAI)
Anxiety sensitivity (ASI)
Pain threshold (degrees Celsius)
Pain threshold rating (NRS)


Stationary Bicycle (n = 20) Lumbar Extension (n = 20) Spinal Manipulation (n = 20)


23.9 (3.4)
12(60%)
68.9 (18.5)
82.6 (16.7)
7.6 (3.1)
45.3 (10.4)
19.8 (7.6)
44.7 (2.4)
25.0 (21.0)


24.1 (2.6)
14(70%)
64.0 (21.8)
75.1 (13.3)
7.2 (3.7)
45.5 (I 1.6)
16.0 (7.1)
45.4 (2.2)
28.8 (19.0)


Key
All data are reported as mean (standard deviation) ratings, unless otherwise indicated.
NRS = Numerical rating scale
FPQ = Fear of Pain Questionnaire
CSQ-R = Coping Strategies Questionnaire-Revised
STAI = State Trait Anxiety Inventory
ASI = Anxiety Sensitivity Index


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24.1 (3.6)
14(70%)
59.7 (25.9)
77.5 (22.6)
7.5 (3.8)
45.2 (10.7)
16.0 (7.2)
44.8 (2.5)
21.3 (15.1)


p-value

0.975
0.741
0.436
0.406
0.955
0.996
0.230
0.589
0.443


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Table 2: First pain hypoalgesia for stationary bicycle, lumbar extension, and spinal manipulation.


Stationary Bicycle
(n = 20)


Lumbar Extension
(n = 20)


Spinal Manipulation
(n = 20)


Partial Eta-square# p-value#


Lumbar Innervated*
NRS Change @ 47C 13.2 (17.2)$
NRS Change @ 49C 1.2 (20.2)
Cervical Innervated^
NRS Change @ 47C -3.0 (13.7)
NRS Change @ 49C 1.9 (9.0)


12.9 (17.9)$
6.3 (22.4)

0.3 (11.6)
-0.4 (10.1)


23.5 (17.3)$
12.1 (19.7)$

0.3 (10.2)
1.7 (10.8)


Key
NRS = Numerical rating scale
All data are reported as mean (standard deviation) ratings.
Negative numbers indicate increased pain following treatment.
# Significance and partial eta-square estimate are for the interaction between type of treatment and first pain hypoalgesia
*- Significant overall main effect for lower extremity hypoalgesia at 47C (F,s57 = 53.8, p < 0.001) and at 49C (F,s57= 5.9, p = 0.018)
$ Significant within group effect for hypoalgesia (p < 0.05)
^ No significant main effect for upper extremity hypoalgesia at 47C (F,s57 = 0.4, p = 0.525) and at 49C (F,s57 = 0.6, p = 0.424)


hypoalgesic response. The implication of this finding is
that psychological influences on SMT hypoalgesic
response were likely not present, or only a minor influ-
ence.

Our findings suggests SMT hypoalgesia is potentially a
local neurophysiological phenomenon in asymptomatic
subjects, corroborating with other studies demonstrating
local SMT effects for EMG activity [57,581 and inflamma-
tion control [591. However it must also be considered that
the literature supports the potential of a central mecha-
nism for SMT hypoalgesia. Specifically, it has been pro-


O Lumbar Innervated Area
nO Cervical Innervated Area


Stationary Bicyle


Lumbar Extension


Spinal Manipulation*


Figure 2
Temporal summation hypoalgesia for stationary
bicycle, lumbar extension, and spinal manipulation.
Figure 2 Key Positive numbers indicate hypoalgesia Error
bars are I standard error * indicates statistically signifi-
cant (p < 0.05) difference in intervention for pain sensitivity
in lower extremity area.


posed that SMT hypoalgesia is a result of the activation of
endogenous descending pain inhibitory systems medi-
ated through the periaqueductal gray region of the mid-
brain [601. In a human study this central mechanism was
supported by Vincenzino et al[611 who reported
hypoalgesia from cervical manipulation was significantly
correlated (r = 0.82) with sympathoexcitation. In an ani-
mal study this central mechanism was supported by Sykba
et al [621 who reported hypoalgesia from knee manipula-
tion was not affected by local spinal blockade of GABA or
opioid receptors. Therefore, the current literature provides
available evidence suggesting SMT hypoalgesia may be
resultant of local and/or central mechanisms.

Our second purpose was to investigate whether SMT
hypoalgesia differed from physical activity for first pain
response or temporal summation. This purpose adds to
the existing literature because previous studies of SMT
hypoalgesia have not included these clinically relevant
comparisons and have not used protocols that differenti-
ated between A-delta and C-fiber mediated pain percep-
tion [24]. Our results provided information supporting
SMT as a "counter-irritant" to inhibit peripheral noxious
stimuli at the dorsal horn [7]. SMT appeared to have a
general counter-irritant effect on A-delta fiber mediated
pain perception (first pain response). SMT had a consist-
ent hypoalgesic effect on A-delta fiber mediated hypoalge-
sia, while stationary bicycle riding and lumbar extension
exercise hypoalgesic effects were noted only at 47 C. SMT
appeared to have a specific counter-irritant effect on C-
fiber mediated pain perception (temporal summation), as
SMT hypoalgesia was greater than bicycle riding and
trended toward being greater than lumbar extension exer-
cise.

The specific hypoalgesic effect on C-fiber mediated pain
perception is an intriguing finding and could provide par-


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Variable


0.101
0.268

0.645
0.720


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Table 3: Associations among pain threshold, psychological variables, and lumbar innervated hypoalgesic responses for subjects
receiving spinal manipulation.


Temporal Summation


Fear of Pain (FPQ)
Pain catastrophizing (CSQ-R)
Anxiety (STAI)
Anxiety sensitivity (ASI)
Pain threshold (degrees Celsius)
Pain threshold rating (NRS)


-0.20 (p = 0.401)
-0.08 (p = 0.750)
-0.16 (p = 0.499)
0.21 (p= 0.370)
-0.26 (p = 0.273)
0.05 (p = 0.843)


First Pain @ 47C

0.01 (p = 0.972)
0.18 (p = 0.442)
-0.19 (p = 0.422)
0.25 (p = 0.292)
0.11 I (p = 0.656)
-0.19 (p = 0.436)


First Pain @ 49C

-0.08 (p = 0.732)
0.10 (p = 0.686)
-0.31 (p = 0. 178)
-0.10 (p = 0.674)
0.14 (p = 0.545)
-0.14 (p = 0.549)


Key
NRS = Numerical rating scale
FPQ = Fear of Pain Questionnaire
CSQ-R = Coping Strategies Questionnaire-Revised
STAI = State Trait Anxiety Inventory
ASI = Anxiety Sensitivity Index

tial explanation for the clinical effectiveness of SMT.
Numerous basic studies have suggested that central sensi-
tization of pain is a specific neurophysiological mecha-
nism associated with the development and maintenance
of chronic pain syndromes [63-68]. Wind-up results from
tonic, peripheral nociceptive C-fiber input and is an exam-
ple of central sensitization that occurs within dorsal horn
cells. This input activates NMDA and substance P recep-
tors in wide dynamic range and nociceptive specific cells.
Then, the tonic activation of these cells induces a central
hyperalgesia mediated at the spinal cord level, such that
subsequent evoked pain stimuli are relayed from the dor-
sal horn as increasing in intensity, despite their being of
standard amplitude. In basic models, this temporal
parameter (increasing frequency of nociceptive input) is a
primary factor in eliciting wind-up [65].

Direct measurement of wind-up is not feasible in human
subjects, but temporal summation of thermal stimuli is an
accepted behavioral measure of wind-up [28]. The use of
temporal summation as a proxy measure of wind-up is
supported by human studies that demonstrate an increase
in the frequency of standard nociceptive input increases
the report of pain perception [29,30,45]. Specifically,
thermal input at .33 Hz or less tends to induce temporal
summation in humans, while input at .20 Hz or greater
does not [28]. The results of the present study indicated
that SMT reduced temporal summation, suggesting a
potential underlying effect of SMT is the inhibition of dor-
sal horn wind-up [7]. Inhibition of dorsal horn wind-up
would mean the individual was less likely to develop
chronic LBP, at least chronic LBP caused by this particular
pain mechanism. It should be noted that this explanation
is speculative at this time, as only one study directly links
temporal summation with chronic LBP [69]. One inter-
pretation of these data is that SMT has the potential of
inhibiting dorsal horn windup from peripheral noxious
stimuli. While this an intriguing explanation, we acknowl-
edge that these findings may also be explained by other


unrelated factors, such as non-specific effects related to
differences in active and passive interventions.

This experimental model offers several advantages in the
study of SMT hypoalgesia. The use of thermal stimuli
allowed us to precisely control levels of nociceptive input
and differentiate this input based on fiber type. The use of
asymptomatic subjects eliminated confounding of the
hypoalgesic response from clinical conditions and pain
medications. However, there are also several limitations
to consider when interpreting this study. First, although
use of asymptomatic subjects offers advantages, these
findings cannot be directly generalized to patients with
LBP. In patients with LBP a wider range of psychological
scores would be expected, potentially making them more
robustly related to hypoalgesia from SMT. Also, patients
with LBP experience ongoing, nociceptive input that is
likely to result in enhanced temporal summation in com-
parison to asymptomatic controls, thereby interacting
with the proposed mechanisms of SMT. Second, this study
only tested the immediate hypoalgesic effects of SMT and
utilized standard treatment parameters that did not
mimic clinical settings. This methodology was necessary
to provide the internal validity to detect a short-term
hypoalgesic response, however this methodology also
means that no assumptions can be made about longer-
term hypoalgesic effects or the effect of these particular
interventions applied under different parameters. Third,
we did not include sham SMT in this study, so we were
unable to account for hypoalgesic effects associated with
the specific expectation of SMT being a successful inter-
vention for pain relief in lumbar innervated areas. Fourth,
we did not report joint cavitation in this study because
previous work demonstrated considerable variability in
the location of cavitation for lumbar SMT [70], and expe-
riencing cavitation does not appear to affect EMG activity
[13] or pain outcomes [71,721. Last, although we did
implement a comparison group (bicycle), we did not uti-
lize a control group in our current design. This methodo-


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logical selection means that non-specific effects related to
differences in active (bicycle and prone press ups) and
passive (SMT) interventions are a viable alternate explana-
tion to our findings.

Conclusion
The finding that SMT may have a local hypoalgesic effect
specific to C-fiber mediated input for asymptomatic sub-
jects adds to the previous literature and provides direction
for future study. First, this experiment should be repro-
duced in patients with LBP that have not yet received
other pain treatments. Such studies will provide impor-
tant information on whether this potential pain inhibit-
ing mechanism is also observed in patient populations.
Second, future studies should include longer follow-up
times and investigate the dose-response relationships
between SMT and hypoalgesia. This topic has been under-
reported in the SMT literature [24] and such studies will
indicate the duration of SMT hypoalgesia and the mini-
mum dosage to achieve optimal SMT hypoalgesia. Third,
future studies should include control groups and tech-
niques that block peripheral nociceptive input at the level
of the dorsal horn. Inclusion of such methodology will
allow future researchers to confirm or refute our mecha-
nistic interpretation of these findings.

Abbreviations
SMT Spinal manipulative therapy

LBP Low back pain

Competing interests
The authors) declare that they have no competing inter-
ests.

Authors' contributions
All authors read, edited, and approved the final version of
the manuscript.

SZG was responsible for the initial conception of the
research question, securing funding, supervising the pro-
tocol, data analysis, and manuscript preparation.

MDB and MER were responsible for modifying the
research question and critically reviewing earlier versions
of the manuscript.

GZ and JEB were responsible for administering the proto-
col and critically reviewing earlier versions of the manu-
script.

Acknowledgements
SZG received start-up support from the College of Public Health and
Health Professions at the University of Florida.


JEB received support from the National Institutes of Health T-32 Neural
Plasticity Research Training Fellowship (T32HD043730).

Kelli Eisenbrown assisted with data collection and data entry.

Megan Hurlburt and Julia Villa assisted with data collection.

Gabrielle Shumrak assisted with data entry.

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