Journal Pre-proof

Changes in pressure pain threshold and temporal summation in rapid responders

and non-rapid responders after lumbar spinal manipulation and sham: A secondary
analysis in adults with low back pain

Sasha L. Aspinall, Charlotte Leboeuf-Yde, Sarah J. Etherington, Bruce F. Walker

PII: S2468-7812(19)30338-8
DOI: https://doi.org/10.1016/j.msksp.2020.102137
Reference: MSKSP 102137

To appear in: Musculoskeletal Science and Practice

Received Date: 26 July 2019

Revised Date: 5 February 2020
Accepted Date: 23 February 2020

Please cite this article as: Aspinall, S.L., Leboeuf-Yde, C., Etherington, S.J., Walker, B.F., Changes
in pressure pain threshold and temporal summation in rapid responders and non-rapid responders
after lumbar spinal manipulation and sham: A secondary analysis in adults with low back pain,
Musculoskeletal Science and Practice (2020), doi: https://doi.org/10.1016/j.msksp.2020.102137.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition
of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of
record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that,
during the production process, errors may be discovered which could affect the content, and all legal
disclaimers that apply to the journal pertain.

© 2020 Published by Elsevier Ltd.

Changes in pressure pain threshold and temporal summation in rapid

responders and non-rapid responders after lumbar spinal manipulation

and sham: A secondary analysis in adults with low back pain

Sasha L Aspinall,a,c Charlotte Leboeuf-Yde,a,b,d Sarah J Etherington,a,e Bruce F Walkera,f

a
College of Science, Health, Engineering and Education, Murdoch University, Perth, Western
Australia
b
Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark
c
Corresponding author, Email: sasha.aspinall@murdoch.edu.au, Address: Murdoch University, 90
South St, Murdoch WA 6150, Australia, Phone: +61 (0)8 9360 2114.
d
Email: clyde@health.sdu.dk
e
Email: s.etherington@murdoch.edu.au
f
Email: bruce.walker@murdoch.edu.au

Conflict of Interest
All authors declare that they have no competing interests.

Ethical Approval
This study had ethical approval from the Murdoch University Human Research Ethics Committee
(approval 2017/177).

Funding
This study was funded by an intra-mural grant from the School of Health Professions, Murdoch
University, Western Australia. The funding source had no involvement in study design, analysis,
interpretation, or manuscript preparation.

Clinical Trials Registry

This trial was prospectively registered with ANZCTR (ACTRN12617001094369).

Contributors
We would like to thank Ms Angela Jacques for her biostatistical assistance.

1
 ABSTRACT
Background: People with LBP who experience rapid improvement in symptoms after spinal

manipulative therapy (SMT) are more likely to experience better longer-term outcomes compared to

those who don’t improve rapidly. It is unknown if short-term hypoalgesia after SMT could be a

relevant finding in rapid responders.

Objectives: We aimed to explore whether rapid responders had different short-term pressure pain

threshold (PPT) and temporal summation (TS) outcomes after SMT and sham compared to non-rapid

responders.

Methods: This was a planned secondary analysis of a randomised controlled trial that recruited 80

adults with LBP (42 females, mean age 37 yrs). PPT at the calf, lumbar spine, and shoulder and TS at

the hands and feet were measured before and three times over 30 minutes after a lumbar SMT or

sham manipulation. Participants were classified as rapid responders or non-rapid responders based

on self-reported change in LBP over the following 24 hours.

Results: Shoulder PPT transiently increased more in the rapid responders than non-rapid responders

immediately post-intervention only (between-group difference in change from baseline =

0.29kg/cm2, 95% CI 0.02-0.56, p = .0497). There were no differences in calf PPT, lumbar PPT, hand

TS, or foot TS based on responder status.

Conclusions: Hypoalgesia in shoulder PPT occurred transiently in the rapid responders compared to

the non-rapid responders. This may or may not contribute to symptomatic improvement after SMT

or sham in adults with LBP, and may be a spurious finding. Short-term changes in TS do not appear

to be related to changes in LBP.

KEYWORDS
Low back pain; responders; quantitative sensory testing; spinal manipulative therapy

1
INTRODUCTION
Background

Low back pain (LBP) has emerged as a major contributor to global disability, and efforts to improve

the management of LBP are imperative [1]. Spinal manipulative therapy (SMT) is a popular

conservative treatment choice for individuals with LBP. Studies generally support the effectiveness

of SMT for LBP, though the size of the treatment effect is typically small [2]. This has led to

speculation that there may be subgroups of individuals who respond better to SMT than others. If

we can identify those who are more likely to respond positively to SMT, it can be better targeted

toward those individuals to improve LBP outcomes and reduce unnecessary care.

Various studies have attempted to characterise those individuals who have a significant positive

response to SMT (or to chiropractic care, of which SMT is typically a major component). A clinical

prediction rule for SMT based on baseline participant characteristics for adults with LBP was

developed [3] and validated [4], however its ability to predict responders has not been replicated in

further studies [5, 6]. Indeed, other studies have found that participant characteristics at baseline

appear to be poor predictors of LBP outcomes after SMT or chiropractic care [7, 8].

It has, however, been shown that adults with LBP who report short-term symptomatic improvement

following SMT (alone or as a component of chiropractic care) are more likely to report better

medium-term outcomes [8-10]. Specifically, self-reported global improvement and reductions in

disability after the first visit of chiropractic care predicts improvement 4 weeks later [9, 10], and self-

reported global improvement and reductions in pain intensity and disability at 1 week predict

improvement at 1 and 3 months [8]. Within-session improvements in pain after physiotherapy

treatment (mostly consisting of manual therapy) also seems to predict between-session

improvement in individuals with LBP [11] and with neck pain [12].

1
There is some research to suggest that people with LBP who respond positively to SMT may exhibit

particular biomechanical characteristics. At baseline, responders may have less severe lumbar facet

joint degeneration and higher water diffusion in intervertebral discs compared to non-responders

[13]. Following SMT, responders have been shown to have an immediate increase in diffusion in

intervertebral discs [13, 14], as well as reduced objective spinal stiffness and altered lumbar

multifidus thickness persisting to 7 days [14], compared to non-responders and asymptomatic

controls. While preliminary, these findings suggest that responders to SMT may be a meaningful

clinical group based on variables other than just symptomatic improvement.

Substantial research has shown short-term hypoalgesia following SMT, though it is at present

unclear whether these changes are greater than when compared to sham manipulation [15, 16].

Hypoalgesia has been suggested as a mechanism that contributes to clinical outcomes after SMT

(and mobilisation) [17]. This is typically measured using quantitative sensory tests (QST), in particular

pressure pain threshold (PPT) and temporal summation (TS). PPT is a measure of how much pressure

is required to cause pain at a testing site [18]. TS is a measure of how much subjective pain intensity

changes over a series of rapid repeated painful stimuli, and is thought to measure ‘wind-up’ or the

excitability of dorsal horn neurons [19]. The clinical relevance of changes in QST after SMT is

unknown, in part because the vast majority of studies only measure before and immediately after

the intervention [15, 16]. Only two studies appear to have investigated the association between

short-term changes in PPT and changes in pain or disability, both finding no significant associations

in shoulder pain populations [20, 21]. Whether hypoalgesia after SMT differs based on symptomatic

change does not appear to have been investigated.

Rationale & Research Questions

Given that an individual’s early response to SMT (alone or as a component of chiropractic care) for

LBP appears to predict their longer-term outcomes, and that some particular biomechanical features

of responders have been observed, it seems reasonable that there may also be specific changes in

2
QST based on an individual’s short-term symptomatic response to SMT. We investigated whether

changes in PPT and TS differed between responders and non-responders, in a planned secondary

analysis of a randomised controlled trial.

Thus, our research question was: How does PPT and TS change in the short term after lumbar SMT

and sham manipulation in those with a rapid symptomatic improvement in LBP compared to those

who do not improve rapidly?

METHODS
This was a planned secondary analysis of data collected from a sham-controlled double-blind

randomised controlled trial. In this manuscript we use a subset of data from the trial, and a summary

of the relevant methods and data are reported here as detailed methods are available elsewhere

[22]. This trial was prospectively registered with ANZCTR (*****) and was approved by the *****

Human Research Ethics Committee (*****).

Participants and Procedure

Participants were volunteers from the general public and a university campus in ***** Australia. We

recruited adults aged 18-60 years who responded affirmatively to the statement “I have been

bothered by LBP at some time in the last 12 months”. We chose to use a subjective definition for LBP

to improve the representativeness of the sample, as SMT is typically used on patients in a primary

care setting who have highly variable intensity and temporal patterns of pain. The concept of

bothersome LBP has been successfully used elsewhere [23-26]. People were excluded if they had any

contraindications to lumbar SMT, had other conditions that might have affected QST measures (e.g.

lower limb radiculopathy), or had received chiropractic treatment in the preceding week.

Baseline data on demographics, LBP intensity, LBP trajectory, pain catastrophising, and anxiety were

collected, and a LBP history and standard physical examination were performed. Practice QST

measurements were performed initially, followed by baseline QST testing. Participants were then

3
randomly allocated to receive one of two interventions, delivered by an experienced chiropractor: a)

a side-lying high-velocity low-amplitude SMT targeting the L5 segment, or b) a sham lumbar

intervention involving similar positioning that has been shown to adequately deceive participants

[27]. Random allocation was achieved using an online random number generator, with group

assignment concealed in opaque sealed envelopes, opened by the clinician delivering each

intervention. The assessor, who was blind to intervention allocation, re-tested QST immediately, as

well as 15 and 30 minutes after the intervention. The same assessor performed all QST. Participants

then rated the subjective global change in LBP since the start of the visit. Finally, participants were

called approximately 24 hours after the visit to again assess subjective global rating of change in LBP.

Questionnaires

Subjective global rating of change in LBP was assessed using a modified Global Back Recovery Scale

(mGBRS). The wording of the original GBRS [28] was modified slightly to ask participants to rate the

overall change in their LBP since starting the study, on a -5 to +5 numerical rating scale (NRS, -5 =

very much worse, 0 = no change, +5 = completely recovered). Global rating of change scales typically

have sound clinimetric properties, including test-retest reliability, responsiveness, and construct

validity [29]. A two-point change is generally accepted as clinically meaningful [29].

For LBP intensity, participants were asked to rate four aspects of their LBP intensity on a 0 to 10 NRS

(0 = no pain, 10 = worst pain imaginable): a) current LBP, b) average LBP (when in pain) over the last

24 hours, c) worst LBP in the last 24 hours, and d) best LBP in the last 24 hours. Participants’ LBP

trajectories were self-reported using the Visual Trajectories Questionnaire-Pain [30], which

contained visual and written descriptions of different patterns of back pain over the last 12 months.

The Pain Catastrophizing Scale was used to assess pain catastrophising, which involves 13 questions

about various negative thoughts and feelings during painful events [31] and has shown internal

consistency and construct validity [32]. The Patient Reported Outcomes Measurement Information

System (PROMIS®) Short Form v1.0 –Anxiety 6a was used to measure anxiety in the previous seven

4
days, with raw scores converted to T-scores for analysis using information available from PROMIS

[33]. This short form has internal consistency with the full questionnaire [34], and it demonstrates

good responsiveness [35] and validity [36].

Responder Status

Participants were categorised as ‘rapid responders’ if they rated their change from the start of the

study as at least +2 on the mGBRS at either the post-intervention time point or 24 hour follow-up, or

both. If a participant did not report at least +2 improvement at either time point, they were

classified as ‘non-rapid responders’.

Quantitative Sensory Testing Procedures

At each round of QST testing, PPT was measured before TS, in total taking roughly 10 minutes. PPT

was measured bilaterally at three sites: a) mid-belly of the medial gastrocnemius, b) 2cm adjacent to

the L5 spinous process, and c) mid-belly of the middle deltoid. A standard protocol was followed [18]

using a calibrated digital pressure algometer (FPIX 50, Wagner Instruments, Connecticut, USA [37])

with a 1cm2 rubber probe. With the probe placed perpendicularly to the skin, pressure was gradually

increased until the participant indicated when they first experienced pain by saying “Yes.” This

pressure was recorded electronically. Three measures were recorded at each test site at each time

point. For data analysis, the final two measures were averaged [38], and sides combined.

TS was measured bilaterally at two sites: a) middle of the anterior transverse arch of the plantar

feet, and b) middle of the proximal transverse arch of the palmar hands. A pinprick device

(Neuropen with Neurotips, Owen-Mumford, Oxfordshire, UK [39]) was used to generate the painful

stimuli by pressing the sharp tip into the testing site until markers on the device lined up. First, a

single stimulus was delivered, followed by five stimuli at a rate of one per second. The participant

rated the severity of pain of the first and the final stimuli on a 101-point NRS (0 = no pain, 100 =

worst pain imaginable). This was repeated three times at each test site at each time point, and TS

5
was calculated by subtracting the mean first pinprick rating from the mean final pinprick rating. We

acknowledge that our TS protocol differs from the protocol defined by the German Neuropathic Pain

Network [40]. The protocol (and device) we used was pre-tested on ten asymptomatic participants,

and appeared to produce acceptable TS [41]. The decision to modify the TS protocol was made

based on concerns about the time and ‘unpleasantness’ burden placed on participants, who were

expected to undergo four rounds of painful QST at six testing sites over a two hour time period. A

train of only five stimuli has been used elsewhere [42], and it has been reported that TS peaks within

the first four stimuli in humans [19].

Statistical Analysis

The sample size calculation for the primary analysis associated with the trial [22] was sufficient for

this secondary analysis. Eighty LBP participants were recruited to detect a 15% change in lumbar

spine PPT (effect size of 0.64) between two groups, with 80% power and alpha at 0.05 [43, 44].

Initially, we tested potential modifying factors (sex, age, pain catastrophising, anxiety, and baseline

LBP intensity) using univariate linear regression. Age and sex were statistically relevant modifiers,

and were included as fixed effects in the final models. We also chose to include intervention group

as a fixed effect, since the intervention may have affected participants’ symptomatic response.

Baseline LBP intensity and whether a second thrust was delivered during the intervention were also

tested as fixed effects in the final models and found not to be relevant modifiers. PPT and TS were

both skewed left and had several outliers on graphical inspection. We analysed longitudinal PPT and

TS data based on responder status using generalised linear mixed models with log link (to account

for skewness) and linear mixed models. The models used random intercept subject effects and

random slope time effects, with fixed effects of sex, age, and intervention group. Contrasts were

used for between-group effect sizes.

6
We report PPT and TS data with adjusted marginal means, 95% confidence intervals, and p values,

with p <.05 considered statistically significant. We used Stata/IC v15.1 (StataCorp, USA) for all

analyses.

RESULTS
Eighty-one volunteers participated in the study from Oct 2017 to July 2018. We excluded one

participant from analyses as we were unable to contact them for the 24hr follow-up call. See Figure

1 for a participant flow chart. Errors with computer recording led to some missing PPT data. Two

participants were missing all baseline PPT data, and three further participants were missing all 30

minute PPT data. These data were not imputed since mixed models use maximum likelihood

estimation methods, which allow for inclusion of all participants despite missing data. Six

participants had either the second or third individual PPT measurement at a single timepoint and

test site missing. These data were imputed by using whichever measurement at that timepoint was

recorded. E.g. if the third measurement at 15 minutes was missing, then the second measurement

was used (instead of an average of the second and third).

Mild adverse events were reported by nine participants, which included post-treatment soreness,

increased LBP, and referred pain into the thigh. All of these spontaneously resolved within several

days.

Participant Characteristics

In total, 35 participants met the criteria to be classified as rapid responders, while 45 were classified

as non-rapid responders. There were no statistically significant differences between responder

groups in baseline characteristics or baseline PPT and TS. See Table 1 for baseline participant

characteristics.

7
Figure 1. Participant flow chart.

8
Table 1. Baseline participant characteristics.
Rapid responders (n=35) Non-rapid responders (n=45)

Age in years, mean (SD, range) 35 (SD 12, 18-57) 37 (SD 12, 18-58)
Sex 21 female (60%), 14 male (40%) 21 female (47%), 24 male (53%)
11 episodic LBP (31%), 24 12 episodic LBP (27%), 33
Baseline LBP trajectory
persistent LBP (69%) persistent LBP (73%)
LBP severity on 0-10 NRS, median (IQR,
range)
Current LBP 3.00 (IQR 3.00, 0-7) 2.00 (IQR 2.00, 0-6)
Average LBP in previous 24hrs 4.00 (IQR 3.00, 0-8) 4.00 (IQR 2.00, 0-8)

Worst LBP in previous 24hrs 5.00 (IQR 4.00, 0-10) 5.00 (IQR 4.00, 0-8)
Best LBP in previous 24hrs 1.00 (IQR 2.00, 0-7) 1.00 (IQR 2.00, 0-5)
Pain Catastrophizing Scale score (0-52),
12.74 (SD 9.96, 0-40) 14.96 (SD 9.18, 0-40)
mean (SD, range)
PROMIS Anxiety T-score, mean (SD,
53.63 (SD 8.22, 39.1-72.7) 53.72 (SD 9.50, 39.1-74.1)
range)
Intervention group 19 SMT (54%), 16 sham (46%) 21 SMT (47%), 24 sham (53%)
2
Calf PPT (kg/cm ), median (IQR) 3.54 (IQR 2.80) 3.85 (IQR 3.55)
2
Lumbar PPT (kg/cm ), median (IQR) 4.30 (IQR 5.19) 4.14 (IQR 4.04)
2
Shoulder PPT (kg/cm ), median (IQR) 2.37 (IQR 2.27) 2.55 (IQR 2.30)
Hand TS (0-100 NRS), median (IQR) 5.33 (IQR 16.88) 4.67 (IQR 9.08)
Feet TS (0-100 NRS), median (IQR) 12.25 (IQR 16.42) 8.25 (IQR 15.25)
Abbreviations: IQR = interquartile range, LBP = low back pain, NRS = numerical rating scale, PPT=
pressure pain threshold, SD = standard deviation, SMT = spinal manipulative therapy, TS = temporal
summation.

Research Question

There was a statistically significant time by responder group interaction in shoulder PPT from

baseline to immediately post-intervention. Both the rapid responders and non-rapid responders had

a statistically significant increase in shoulder PPT (decreased sensitivity) over this time (rapid

responders: 0.45 kg/cm2, CI 0.23-0.68, p=<.01; non-rapid responders: 0.17 kg/cm2, CI 0.01-0.32,

p=.04), but the significant interaction indicates that the rapid responders group had a greater

increase than the non-rapid responders. There were no other significant time by responder group

interactions for PPT or TS. See Table 2 and Figure 2 for full results.

9
Table 2. Within-group and between-group results for pressure pain threshold and temporal
summation.
Adjusted mean (CI) Time x Group interaction
Adjusted mean between-
Non-rapid
Rapid responders group difference in p value
responders
Testing site and time change from baseline (CI)
2
Calf PPT (kg/cm )
Baseline 4.31 (3.54 – 5.08) 4.30 (3.64 – 4.95) - -
Immediate 4.38 (3.63 – 5.13) 4.33 (3.70 – 4.97) 0.03 (-0.31 – 0.37) .86
15min 4.26 (3.54 – 4.98) 4.40 (3.76 – 5.04) -0.15 (-0.56 – 0.26) .47
30min 4.52 (3.76 – 5.29) 4.43 (3.79 – 5.08) 0.08 (-0.44 – 0.59) .78
2
Lumbar PPT (kg/cm )
Baseline 5.47 (4.35 – 6.60) 5.12 (4.22 – 6.02) - -
Immediate 5.90 (4.73 – 7.07) 5.17 (4.28 – 6.05) 0.39 (-0.03 – 0.81) .09
15min 6.00 (4.81 – 7.18) 5.14 (4.27 – 6.02) 0.51 (-0.04 – 1.05) .08
30min 5.70 (4.56 – 6.85) 5.16 (4.27 – 6.05) 0.20 (-0.50 – 0.90) .59
Shoulder PPT
2
(kg/cm )
Baseline 3.03 (2.48 – 3.58) 2.92 (2.47 – 3.37) - -
.05* (actual
Immediate 3.48 (2.87 – 4.10) 3.09 (2.63 – 3.55) 0.29 (0.02 – 0.56)
value .0497)
15min 3.27 (2.69 – 3.85) 3.07 (2.61 – 3.53) 0.09 (-0.24 – 0.42) .63
30min 3.22 (2.63 – 3.81) 3.12 (2.63 – 3.60) -0.01 (-0.44 – 0.42) .95
Hand TS (0-100 NRS)
Baseline 10.52 (6.67 – 14.36) 7.39 (4.00 – 10.77) - -
Immediate 10.32 (6.62 – 14.02) 5.99 (2.73 – 9.24) 1.20 (-1.24 – 3.64) .34
15min 10.42 (6.84 – 14.00) 6.00 (2.85 – 9.16) 1.28 (-1.29 – 3.85) .33
30min 7.32 (3.83 – 10.82) 5.34 (2.26 – 8.43) -1.15 (-3.94 – 1.63) .42
Feet TS (0-100 NRS)
Baseline 14.74 (10.23 – 19.26) 11.63 (7.65 – 15.61) - -
Immediate 12.83 (8.83 – 16.82) 9.36 (5.84 – 12.87) 0.36 (-2.62 – 3.33) .82
15min 10.15 (6.58 – 13.72) 8.03 (4.88 – 11.17) -0.99 (-4.49 – 2.52) .58
30min 9.03 (5.73 – 12.32) 7.19 (4.30 – 10.09) -1.28 (-5.53 – 2.96) .55
* p < .05. Abbreviations: CI = 95% confidence interval, NRS = numerical rating scale, SMT = spinal
manipulative therapy, TS = temporal summation.

10
Figure 2. Change over time with 95% confidence intervals for pressure pain threshold and
temporal summation after intervention, by responder status.
Abbreviations: PPT = pressure pain threshold, TS = temporal summation. * Statistically significant time
by responder group interaction.

DISCUSSION
To the best of our knowledge, no prior studies have investigated whether rapid responders to a

lumbar SMT or sham intervention have a different response in QST outcomes compared to non-

rapid responders in adults with LBP. Shoulder PPT demonstrated a borderline statistically significant

increase over time, which was greater in the rapid responder group compared to the non-rapid

responders but only occurred immediately post-intervention and did not persist to 15 or 30 minutes.

Changes in calf and lumbar PPT did not appear to differ based on responder status, nor did changes

in TS. The variability in both PPT and TS was large.

11
Our results suggest potential limited differences in short-term change in PPT based on responder

status, particularly hypoalgesia in shoulder PPT in the rapid responders group compared to non-

responders. Short-term increases in PPT may be a contributory mechanism in symptomatic

improvement in LBP after a brief manual therapy intervention, as suggested by Bialosky et al. [17].

Since shoulder PPT was affected, this could support the theory that a central pain-relieving

mechanism may be influencing mechanical pain. However, a central mechanism would also be

expected to affect PPT at the calf and lumbar spine. This was not observed in our study and thus the

reason for our observation is unclear. It is possible that the difference between groups in change in

shoulder PPT may be a spurious finding, especially since the p value was close to .05, the lower 95%

confidence interval approaches (but does not meet) zero, and the effect size appears to be small at

0.29 kg/cm2.

It is also possible that a short-term increase in shoulder PPT may reflect processes that are unrelated

to symptomatic change, especially since the changes we observed did not persist to 15 minutes

post-intervention. Our study was not designed to establish a causal relationship between

hypoalgesia and symptomatic change. Studies measuring changes in PPT over longer time periods

(e.g. over days or weeks) may shed more light on the potential relationship between changes in PPT

after an intervention and responder status in LBP populations.

Based on our data, short-term changes in TS do not appear to differ based on responder status and

thus symptomatic responses may not be tied to changes in the excitability of dorsal horn neurons

after a brief manual therapy intervention. Others have speculated that SMT is capable of modulating

central sensitisation processes, in part based on studies observing decreases in TS short-term after

SMT [45, 46]. This study offers preliminary evidence that short-term improvement in LBP is not

related to short-term changes in TS.

Interestingly, the number of people who received lumbar SMT and sham was similar in both

responder groups. Our study is unable to determine whether changes in PPT based on responder

12
status are related to which intervention the participant received. However, intervention group was

not a statistically significant fixed effect in the mixed models we used to analyse the data. This

suggests that the PPT and TS data were not substantially influenced by intervention group. A study

with a larger sample size would likely be needed to more thoroughly investigate complex three-way

interactions between change over time, responder status, and intervention. The addition of a no-

treatment group would be valuable in determining whether any changes in QST over time based on

short-term symptomatic improvement are related to natural history or to receiving treatment

specifically.

Methodological Considerations

The participants in this study are likely a heterogeneous group of people with LBP, since participants

could have either episodic or persistent LBP. This may be considered as both a strength and a

limitation. Four participants had no pain in the 24 hours prior to participating. They were still

included in the analyses since the mGBRS, which we used to classify participants as either rapid

responders or non-rapid responders, is not specific to pain intensity and thus changes in other

subjective aspects of LBP, such as discomfort and stiffness, likely contribute to a participant’s

perceived change in LBP. We also note that baseline subjective LBP intensity was not a significant

modifier in the statistical models. It is also important to note that we did not follow our participants

over multiple visits with the same treatment, thus we cannot confirm whether our rapid responders

were more likely to experience longer-term improvement.

The interventions used in this study have restricted generalisability for several reasons. The

interventions were delivered to a pre-specified vertebral level, were allocated randomly, and were

very brief. It is unknown how changes in PPT or TS based on responder status might differ after

pragmatic manual therapy treatment for LBP that more closely reflects typical care delivered by

health care professionals.

13
 CONCLUSION
We observed a small immediate increase in shoulder PPT (decreased sensitivity), but not lumbar or

calf PPT, in individuals who experienced a rapid improvement in LBP symptoms within 24 hours of

receiving either a lumbar SMT or sham manipulation, compared to those who did not improve.

Hypoalgesia in PPT may or may not contribute to symptomatic improvement in those rapid

responders, and may in fact be a spurious finding. There were no differences in change in TS after

intervention based on whether participants’ LBP symptoms improved rapidly or not, and therefore

changes in TS may not be related to short-term symptom improvement in this population.

ABBREVIATIONS
LBP = low back pain, mGBRS = modified global back recovery scale, NRS = numerical rating scale, PPT
= pressure pain threshold, QST = quantitative sensory testing, SMT = spinal manipulative therapy, TS
= temporal summation.

CONTRIBUTORS
We would like to thank Ms ***** for her biostatistical assistance.

REFERENCES
1. Hartvigsen J, Hancock MJ, Kongsted A, Louw Q, Ferreira ML, Genevay S, et al. What low back
pain is and why we need to pay attention. The Lancet. 2018;391(10137):2356-67. doi:
10.1016/S0140-6736(18)30480-X.
2. Coulter ID, Crawford C, Hurwitz EL, Vernon H, Khorsan R, Suttorp Booth M, et al.
Manipulation and mobilization for treating chronic low back pain: a systematic review and meta-
analysis. Spine J. 2018;18(5):866-79. doi: 10.1016/j.spinee.2018.01.013.
3. Flynn T, Fritz J, Whitman J, Wainner R. A Clinical Prediction Rule for Classifying Patients with
Low Back Pain Who Demonstrate Short-Term Improvement With Spinal Manipulation. Spine (Phila
Pa 1976). 2002;27(24):2835-43. doi: 10.1097/00007632-200212150-00021.
4. Childs JD, Fritz JM, Flynn TW, Irrgang JJ, et al. A Clinical Prediction Rule To Identify Patients
with Low Back Pain Most Likely To Benefit from Spinal Manipulation: A Validation Study. Ann Intern
Med. 2004;141(12):920-8. doi: 10.7326/0003-4819-141-12-200412210-00008.
5. Apeldoorn AT, Ostelo RW, van Helvoirt H, Fritz JM. A randomized controlled trial on the
effectiveness of a classification-based system for subacute and chronic low back pain. Spine (Phila Pa
1976). 2012;37(16):1347-56. doi: 10.1097/BRS.0b013e31824d9f2b.
6. Hancock MJ, Maher CG, Latimer J, Herbert RD, McAuley JH. Independent evaluation of a
clinical prediction rule for spinal manipulative therapy: a randomised controlled trial. Eur Spine J.
2008;17(7):936-43. doi: 10.1007/s00586-008-0679-9.

14
7. Vavrek D, Haas M, Neradilek MB, Polissar N. Prediction of pain outcomes in a randomized
controlled trial of dose–response of spinal manipulation for the care of chronic low back pain. BMC
Musculoskelet Disord. 2015;16(1):1-13. doi: 10.1186/s12891-015-0632-0.
8. Peterson CK, Bolton J, Humphreys BK. Predictors of improvement in patients with acute and
chronic low back pain undergoing chiropractic treatment. J Manipulative Physiol Ther.
2012;35(7):525-33. doi: 10.1016/j.jmpt.2012.06.003.
9. Axen I, Rosenbaum A, Robech R, Larsen K, Leboeuf-Yde C. The Nordic Back Pain
Subpopulation Program: Can Patient Reactions to the First Chiropractic Treatment Predict Early
Favorable Treatment Outcome in Nonpersistent Low Back Pain? J Manipulative Physiol Ther.
2005;28(3):153-8. doi: 10.1016/j.jmpt.2005.02.007.
10. Axén I, Rosenbaum A, Röbech R, Wren T, Leboeuf-Yde C. Can patient reactions to the first
chiropractic treatment predict early favorable treatment outcome in persistent low back pain? J
Manipulative Physiol Ther. 2002;25(7):450-4. doi: 10.1067/mmt.2002.126473.
11. Hahne AJ, Keating JL, Wilson SC. Do within-session changes in pain intensity and range of
motion predict between-session changes in patients with low back pain? Australian Journal of
Physiotherapy. 2004;50(1):17-23. doi: 10.1016/S0004-9514(14)60244-0.
12. Tuttle N, Laakso L, Barrett R. Change in impairments in the first two treatments predicts
outcome in impairments, but not in activity limitations, in subacute neck pain: an observational
study. Aust J Physiother. 2006;52(4):281-5. doi: 10.1016/S0004-9514(06)70008-3.
13. Wong AYL, Parent EC, Dhillon SS, Prasad N, Samartzis D, Kawchuk GN. Differential patient
responses to spinal manipulative therapy and their relation to spinal degeneration and post-
treatment changes in disc diffusion. Eur Spine J. 2019;28(2):259-69. doi: 10.1007/s00586-018-5851-
2.
14. Wong AYL, Parent EC, Dhillon SS, Prasad N, Kawchuk GN. Do participants with low back pain
who respond to spinal manipulative therapy differ biomechanically from nonresponders, untreated
controls or asymptomatic controls? Spine (Phila Pa 1976). 2015;40(17):1329-37. doi:
10.1097/BRS.0000000000000981.
15. Aspinall SL, Leboeuf-Yde C, Etherington SJ, Walker BF. Manipulation-induced hypoalgesia in
musculoskeletal pain populations: A systematic critical review and meta-analysis. Chiropr Man Ther.
2019;27(7). doi: 10.1186/s12998-018-0226-7.
16. Honoré M, Leboeuf-Yde C, Gagey O. The regional effect of spinal manipulation on the
pressure pain threshold in asymptomatic subjects: a systematic literature review. Chiropr Man Ther.
2018;26(1):11. doi: 10.1186/s12998-018-0181-3.
17. Bialosky JE, Bishop MD, Price DD, Robinson ME, George SZ. The mechanisms of manual
therapy in the treatment of musculoskeletal pain: a comprehensive model. Manual Ther.
2009;14(5):531-8. doi: 10.1016/j.math.2008.09.001.
18. Fischer AA. Pressure algometry over normal muscles. Standard values, validity and
reproducibility of pressure threshold. Pain. 1987;30(1):115-26.
19. Herrero JF, Laird JMA, Lopez-Garcia JA. Wind-up of spinal cord neurones and pain sensation:
much ado about something? Prog Neurobiol. 2000;61(2):169-203. doi: 10.1016/S0301-
0082(99)00051-9.
20. Coronado RA, Bialosky JE, Bishop MD, Riley 3rd JL, Robinson ME, Michener LA, et al. The
Comparative Effects of Spinal and Peripheral Thrust Manipulation and Exercise on Pain Sensitivity
and the Relation to Clinical Outcome: A Mechanistic Trial Using a Shoulder Pain Model. J Orthop
Sports Phys Ther. 2015;45(4):252-64. doi: 10.2519/jospt.2015.5745.
21. Kardouni JR, Shaffer SW, Pidcoe PE, Finucane SD, Cheatham SA, Michener LA. Immediate
changes in pressure pain sensitivity after thoracic spinal manipulative therapy in patients with
subacromial impingement syndrome: A randomized controlled study. Manual Ther. 2015;20(4):540-
6. doi: 10.1016/j.math.2014.12.003.
22. Anonymous. 2019a. Details omitted for blinded peer-review.

15
23. Dunn KM, Croft PR. Classification of low back pain in primary care: using "bothersomeness"
to identify the most severe cases. Spine (Phila Pa 1976). 2005;30(16):1887-92. doi:
10.1097/01.brs.0000173900.46863.02.
24. Leboeuf-Yde C, Krüger Jensen R, Wedderkopp N. Persistence of pain in patients with chronic
low back pain reported via weekly automated text messages over one year. BMC Musculoskelet
Disord. 2015;16(1):299. doi: 10.1186/s12891-015-0754-4.
25. Lemeunier N, Leboeuf-Yde C, Kjaer P, Gagey O. Stability of low back pain reporting over 8
years in a general population aged 40/41 years at base-line: Data from three consecutive cross-
sectional surveys. BMC Musculoskelet Disord. 2013;14:270. doi: 10.1186/1471-2474-14-270.
26. Axén I, Bodin L, Bergström G, Halasz L, Lange F, Lövgren PW, et al. Clustering patients on the
basis of their individual course of low back pain over a six month period. BMC Musculoskelet Disord.
2011;12(1):1-10. doi: 10.1186/1471-2474-12-99.
27. Chaibi A, Šaltytė Benth J, Bjørn Russell M. Validation of Placebo in a Manual Therapy
Randomized Controlled Trial. Sci Rep. 2015;5:11774. doi: 10.1038/srep11774.
28. Hush JM, Kamper SJ, Stanton TR, Ostelo R, Refshauge KM. Standardized Measurement of
Recovery From Nonspecific Back Pain. Arch Phys Med Rehabil. 2012;93(5):849-55. doi:
10.1016/j.apmr.2011.11.035.
29. Kamper SJ, Maher CG, Mackay G. Global Rating of Change Scales: A Review of Strengths and
Weaknesses and Considerations for Design. J Man Manip Ther. 2009;17(3):163-70. doi:
10.1179/jmt.2009.17.3.163.
30. Dunn KM, Campbell P, Jordan KP. Validity of the Visual Trajectories Questionnaire for Pain. J
Pain. 2017;18(12):1451-8. doi: 10.1016/j.jpain.2017.07.011.
31. Sullivan MJ. Pain Catastrophizing Scale (PCS). https://eprovide.mapi-
trust.org/instruments/pain-catastrophizing-scale. Accessed 22 Jun 2019.
32. Osman A, Barrios FX, Gutierrez PM, Kopper BA, Merrifield T, Grittmann L. The Pain
Catastrophizing Scale: further psychometric evaluation with adult samples. J Behav Med.
2000;23(4):351-65. doi: 10.1023/A:1005548801037.
33. HealthMeasures. PROMIS Short Form v1.0 - Anxiety 6a.
www.healthmeasures.net/index.php?option=com_instruments&view=measure&id=145&Itemid=99
2. Accessed 22 Jun 2019.
34. Pilkonis PA, Choi SW, Reise SP, Stover AM, Riley WT, Cella D. Item Banks for Measuring
Emotional Distress From the Patient-Reported Outcomes Measurement Information System
(PROMIS®): Depression, Anxiety, and Anger. Assessment. 2011;18(3):263-83. doi:
10.1177/1073191111411667.
35. Schalet BD, Pilkonis PA, Yu L, Dodds N, Johnston KL, Yount S, et al. Clinical validity of PROMIS
Depression, Anxiety, and Anger across diverse clinical samples. J Clin Epidemiol. 2016;73:119-27. doi:
10.1016/j.jclinepi.2015.08.036.
36. Purvis TE, Neuman BJ, Riley III LH, Skolasky RL. Discriminant Ability, Concurrent Validity, and
Responsiveness of PROMIS Health Domains Among Patients With Lumbar Degenerative Disease
Undergoing Decompression With or Without Arthrodesis. Spine (Phila Pa 1976). 2018;43(21):1512-
20. doi: 10.1097/brs.0000000000002661.
37. Wagner Instruments. Force One™ FDIX. www.wagnerinstruments.com/products/force-
gages/digital-force-gages/force-one-fdix. Accessed 24 Jul 2019.
38. Lacourt TE, Houtveen JH, van Doornen LJP. Experimental pressure-pain assessments: Test–
retest reliability, convergence and dimensionality. Scand J Pain. 2012;3(1):31-7. doi:
10.1016/j.sjpain.2011.11.010.
39. Owen Mumford. Neuropen®. www.owenmumford.com/us/healthcare-professionals-
product/neuropen/. Accessed 24 Jul 2019.
40. Rolke R, Baron R, Maier C, Tölle TR, Treede DR, Beyer A, et al. Quantitative sensory testing in
the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference
values. Pain. 2006;123(3):231-43. doi: 10.1016/j.pain.2006.01.041.

16
41. Anonymous. 2019b. Details omitted for blinded peer-review.
42. Anderson RJ, Craggs JG, Bialosky JE, Bishop MD, George SZ, Staud R, et al. Temporal
summation of second pain: Variability in responses to a fixed protocol. Eur J Pain. 2013;17(1):67-74.
doi: 10.1002/j.1532-2149.2012.00190.x.
43. Waller R, Straker L, O'Sullivan P, Sterling M, Smith A. Corrigendum to ‘Reliability of pressure
pain threshold testing in healthy pain free young adults’ [Scand. J. Pain 9 (2015) 38–41]. Scand J Pain.
2016;13:17. doi: 10.1016/j.sjpain.2016.06.008.
44. Waller R, Straker L, O'Sullivan P, Sterling M, Smith A. Reliability of pressure pain threshold
testing in healthy pain free young adults. Scand J Pain. 2015;9:38-41. doi:
10.1016/j.sjpain.2015.05.004.
45. Randoll C, Gagnon-Normandin V, Tessier J, Bois S, Rustamov N, O'Shaughnessy J, et al. The
mechanism of back pain relief by spinal manipulation relies on decreased temporal summation of
pain. Neuroscience. 2017;349:220-8. doi: 10.1016/j.neuroscience.2017.03.006.
46. Zafereo JA, Deschenes BK. The Role of Spinal Manipulation in Modifying Central
Sensitization. J Appl Biobehav Res. 2015;20(2):84-99. doi: 10.1111/jabr.12033.

17
18
Highlights

• We investigated changes in pain sensitivity after spinal manipulation and sham

• We grouped participants based on rapid improvement in low back pain or not

• Pressure pain threshold increased at the shoulder in rapid responders only

• This change may not be clinically meaningful

• Temporal summation decreased in both groups