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Manual Therapy 19 (2014) 281e287

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Manual Therapy
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Systematic review

The effects of spinal mobilizations on the sympathetic nervous

system: A systematic review
Laura Kingston*, Leica Claydon, Steve Tumilty
Centre for Physiotherapy Research, University of Otago, 325 Great King Street, Dunedin 9016, New Zealand

a r t i c l e i n f o a b s t r a c t

Article history: The activity of the sympathetic nervous system is of importance to manual therapists, since the expe-
Received 12 July 2012 rience of pain is associated with sympathetic activity. There has been little exploration into the effects of
Received in revised form mobilizing vertebral segments below the cervical spine. In addition to this, a synthesis of the evidence for
2 April 2014
changes in sympathetic outcome measures has not been completed.
Accepted 3 April 2014
The primary aim of this review was to investigate the effects of spinal mobilizations compared to a
control or placebo on sympathetic outcome measures. The secondary aim was to establish the level of
change, either excitatory or inhibitory, in sympathetic outcome measures. Five electronic databases (Ovid
Spinal manipulation
Best evidence
Medline, Embase, AMED, PEDro, and the Cochrane library; from database inception to May 2012) were
Sympathetic nervous system searched for randomized controlled trials. Two independent raters applied inclusion criteria and rated
Sympathetic outcome measures studies for methodological quality. Seven studies met the inclusion criteria.
Skin conductance All studies demonstrated a consistent increase in sympathetic outcome measures, indicative of sym-
pathetic excitation, irrespective of the segments mobilized. Synthesis of the results established strong
evidence (multiple high-quality randomised controlled trials (RCTs) for a positive change in skin
conductance, respiratory rate, blood pressure, and heart rate among the healthy population. As only one
study investigated changes in a symptomatic population, there was limited evidence (one RCT) for an
increase in skin conductance and decrease in skin temperature. Evidence from this systematic review
supports a sympatho-excitatory response to spinal mobilizations irrespective of the segment mobilized.
Ó 2014 Elsevier Ltd. All rights reserved.

1. Introduction Gate-control mechanisms (Melzack and Wall, 1965) together

with other biomechanical effects (Evans, 2002) formed early hy-
Manual therapy (MT) techniques, which encompass a broad potheses on the mechanisms of therapeutic effects following MT
range of procedures, are commonly used to treat joint restriction interventions. There is general agreement that the response of the
and improve pain outcomes by therapists throughout the world. A sympathetic nervous system (SNS) is part of a much greater, cen-
common form of MT is passive joint mobilization, often referred to trally co-ordinated response to spinal mobilizations. Many authors
as “mobilizations”. For the purposes of this review, spinal mobili- have postulated that an area of the mid brain, the dorsal peri-
zations will refer to graded passive, oscillatory movements applied acqueductal grey area (dPAG), is instrumental in evoking this ac-
to the spine, that move it to the end of its available range (Maitland tivity (Lovick, 1985; Evans, 2002). Other authors have used an
et al., 2001). Other forms of MT commonly used in the clinical anatomical explanation to account for the increase in sympathetic
setting include high-velocity low-amplitude (HVLA) thrust ma- outflow. This theory relates to the anatomical positioning of the
nipulations and mobilizations with movement (MWM’s). To avoid sympathetic trunk and paravertebral ganglia (Petersen et al., 1993),
grouping the effect of different forms of MT techniques together, which is also the basis for theories on regional bias (different
HVLA thrust manipulations and MWMs will not be considered in sympathetic response dependent on the region of the spine). For
this review. example, Harris and Wagnon (1987) demonstrated an increase in
peripheral skin temperature (indicating inhibition of the SNS)
following manipulation of cervical and lumbar vertebrae and a
* Corresponding author. Tel.: þ64 211363822. decrease in peripheral temperature (indicating excitation of the
E-mail address: (L. Kingston). SNS) following manipulation of thoracic vertebrae.
1356-689X/Ó 2014 Elsevier Ltd. All rights reserved.
282 L. Kingston et al. / Manual Therapy 19 (2014) 281e287

The proposal of a multi-system, centrally co-ordinated response Investigations involving MWMs, and HVLA thrust manipula-
is based on observations from numerous studies (Vicenzino et al., tions were excluded from this review. Trials that investigated
1998; Evans, 2002). Increases in heart rate (HR), blood pressure longer-term effects (i.e. more than 24 h) of spinal mobilizations on
(BP) and respiratory rate (RR) following stimulation of the dPAG in the SNS were also excluded.
animal models have been observed (Burnett and Gebhart, 1991).
These changes occurred concurrently with sympathetic excitation 2.3. Selection of studies
and hypoalgesia (Lovick, 1985). Diminished pressure pain thresh-
olds have been consistently demonstrated following different Potentially relevant articles were obtained in full text, and
forms of MT with concurrent sympathetic excitation (McGuiness screened independently by two authors (LK and LC) for inclusion
et al., 1997; Sterling et al., 2001; Cleland et al., 2002; Cleland and and exclusion criteria.
McRae., 2002).
In a review Schmid et al. (2008) found significant support for 2.4. Data extraction
central involvement in diminished pressure-pain thresholds
following cervical spine mobilizations. However, this review was Two authors (LK and ST) independently extracted data from the
limited to studies that investigated cervical segments only. There is studies, using a standardized form (Table 1). Inconsistencies were
ambiguity in the literature regarding the sympathetic response of resolved by discussion between the two authors. Corresponding
other forms of MT, such as HVLA thrust manipulations, in different authors listed on the included articles were contacted for primary
regions of the spine (‘regional bias’) (Kappler and Kelso, 1984; data to complete a meta-analysis, however the study data were not
Harris and Wagnon, 1987; Welch and Boone, 2008). The majority available.
of studies that have reported on this have been poorly controlled
and employed different techniques. However, it raises the possi- 2.5. RCT rating
bility that regional biases might also be present, following spinal
mobilizations. To the best of the authors’ knowledge a systematic The Cochrane Collaboration’s recommended tool for assessing
review of the sympathetic response following spinal mobilizations risk of bias (RoB) was included in this review (Alderson et al., 2004).
in different regions of the spine has not been completed. Systematic The RoB assessment tool incorporates six primary sources for bias,
reviews of RCTs constitute ‘best evidence’ in terms of the validity or and was used independently by two authors (LK and ST) to classify
rigour of the evidence for a particular treatment. Hence, they are the risk of bias in each study as a “high risk”, “low risk” or “unclear
used by clinicians and policy makers to guide decision making. risk”. Differences in opinions were discussed and an agreement on
The primary aim of this review was to evaluate RCTs investi- judgements reached; it was not necessary to consult with the third
gating the effects of spinal mobilizations on SNS outcome mea- author. Refer to Table 2 for an overview of these judgements.
sures, in both healthy and patient populations. The second aim was PEDro, which is the Physiotherapy Evidence Database, contains
to establish the currently available level of evidence (Heymans randomized trials, systematic reviews and clinical practice guide-
et al., 2004) that supports a change in sympathetic outcome lines in physiotherapy. The PEDro rating scale is an 11-point rating
measures. scale used to help individuals quickly assess the internal validity
(criteria 2e9) and statistical interpretability of results from a trial
2. Methods (criteria 10e11). A score of six or above is considered a high-quality
trial, while a score of below six is considered a low-quality trial
This systematic review has been completed in accordance with (Gravare Silbernagel et al., 2001; Roos et al., 2004; Martinez-
internationally recommended guidance; the Preferred Reporting Silvestrin et al., 2005). The maximum score achievable on the
Item for Systematic Reviews and Meta-Analyses (PRISMA) (www. PEDro scale is 10/10; as the first criterion, which assesses the external validity of a trial, is not included in the final score. Each
study was independently rated on this scale by two authors (LK and
2.1. Literature search ST); disagreements were resolved by discussion and an agreement
was reached for differing scores (Table 3).
The following electronic databases were searched for eligible Results of combined studies were also summarized using a best-
trials (from database inception to May 2012): Ovid Medline, evidence synthesis (Heymans et al., 2004). The level of evidence for
Embase, AMED, PEDro and the Cochrane library. Reference lists specific SNS outcome measures was ranked according to the
were also examined to identify any articles not captured in the following criteria:
electronic database search.
The search was restricted to RCTs conducted on humans and  “Strong” evidence: generally consistent findings in multiple
reported in English language. None of the study authors were high-quality RCTs.
contacted to identify additional studies; only published material  “Moderate” evidence: generally consistent findings in one high-
was included. quality RCT, plus one or more low-quality RCTs, or by generally
consistent findings in multiple low-quality RCTs.
2.2. Eligibility criteria  “Limited” or “conflicting” evidence: only one RCT (either high or
low quality) or inconsistent findings in multiple RCTs.
RCTs that investigated at least one sympathetic outcome BP, HR,  “No” evidence: no RCTs.
RR, skin conductance (SC) and skin temperature (ST) during or
immediately following spinal mobilization were included. Spinal 3. Results
mobilizations were accepted in the form of passive accessory
movements (Schmid et al., 2008). The control interventions 3.1. Search strategy
considered acceptable were: no treatment, and/or placebo inter-
vention. Both male and female volunteers between the ages of 18e The combined database search in MEDLINE, AMED and Embase
65 years, in either a healthy or symptomatic population were yielded five RCTs eligible for inclusion in this review. Searches in
considered eligible. PEDro and the Cochrane Controlled Trials register did not add any
Table 1
Data extracted from studies reviewed.

Authors Participants Intervention Control/Comparator Outcome Results

Petersen et al. (1993) 16 Healthy (male) subjects GIII central PA C5 Placebo procedure Skin conductance SC: Significant increase in intervention procedure compared to
(oscillatory technique) Control procedure Skin temperature placebo and control procedures. An increase in the order of
50e60% during intervention steadily decreasing to that of
placebo after. Placebo consistently increased in the order of 30%
during the intervention and 15e20% after.
ST: Significant decrease in intervention procedure compared to
control (change in the order of 1%), no significant difference
between placebo and intervention procedure.
Chiu and Wright (1996) 16 Healthy (male) subjects GIII central PA C5 @ 2 Hz GIII central PA Skin Conductance SC: Significant increase in 2 Hz group compared to control

L. Kingston et al. / Manual Therapy 19 (2014) 281e287

(oscillatory technique) C5 @ 0.5 Hz Placebo Skin temperature and 0.5 Hz. 2 Hz group increased in the order of 50e60%.
ST: No significant difference in ST between 3 groups.
McGuiness et al. (1997) 23 Healthy (male & GIII central PA C5 Placebo procedure Respiratory rate Significant increases in all outcomes in intervention group
female) subjects (oscillatory technique) Control procedure Blood pressure compared to control and placebo procedures. RR increased
Heart rate in the intervention group during treatment by 44%, Diastolic
BP increased by 12.5% and systolic BP increased by 4.5%. HR
increased in the order of 10.5%.
Vicenzino et al. (1998) 24 Healthy subjects GIII left lateral glide C5 Placebo procedure Respiratory rate Significant increase in all outcomes of the intervention
(oscillatory technique) Control procedure Heart rate procedure compared to control and placebo procedures. RR
Blood pressure increased in the intervention group 36% compared to an increase
of 13% and 14% in the placebo and control group respectively.
HR increased in the intervention group 13% compared to
2% and 1% in the placebo and control group respectively. BP
increased in the intervention group by 14% compared to 1% in
the both the placebo and control group.
(Sterling et al., 2001) 30 subjects GIII unilateral PA on Placebo procedure Skin temperature SC: Significant increase in intervention procedure compared
(male & female) e cervical symptomatic side Control procedure Skin conductance to placebo and control procedure. 16% change increase from
pain > 3months (oscillatory technique) Pressure pain baseline in the intervention group.
and dysfunction C5/6 threshold ST: significant decrease in intervention procedure of 1.3 to 2.5%
Thermal pain
Perry and Green (2008) 45 healthy (male) subjects GIII unilateral (left) PA L4/5 @ 2 Hz Placebo group Skin conductance SC: Significant side-specific increase on ipsilateral side in the
(oscillatory technique) Control group intervention group, compared to placebo and control group. 13%
increase from baseline during the intervention.
Jowsey and Perry (2010) 36 healthy (male & GIII rotatory mobilisation T4 @ 0.5 Hz Placebo group Skin conductance SC: Significant side-specific increase in the intervention group
female) subjects (oscillatory technique) compared to the placebo group. Increase in mean percentage
change of 5.74% during the intervention compared to placebo
and 16.84% post intervention compared to placebo.

284 L. Kingston et al. / Manual Therapy 19 (2014) 281e287

Table 2
PEDro scores for each study.

References Criteria 1 Criteria 2 Criteria 3 Criteria 4 Criteria 5 Criteria 6 Criteria 7 Criteria 8 Criteria 9 Criteria 10 Criteria 11 Total

Petersen et al., 1993 Y Y N Y Y N Y N N Y Y 6/10 (high)

Chiu and Wright 1996 Y Y N Y Y N Y N N Y Y 6/10(high)
McGuiness et al., 1997 Y Y N Y Y N Y N N Y Y 6/10 (high)
Vicenzino et al., 1998 Y Y N Y Y N Y N N Y Y 6/10 (low)
Sterling et al., 2001 Y Y N Y Y N Y N N Y Y 6/10(high)
Perry and Green 2008 Y Y Y Y Y N Y Y N Y Y 8/10 (high)
Jowsey and Perry 2010 Y Y N Y Y N Y Y N Y Y 7/10 (high)

further articles. Searching the reference lists of key articles yielded et al., 1998; Perry and Green, 2008; Jowsey and Perry, 2010).
a further two articles (Petersen et al., 1993; McGuiness et al., 1997) Limited evidence for significant changes in SC and ST among the
that were eligible for inclusion, and were not captured in the symptomatic population was established (Sterling et al., 2001). All
electronic search. changes were excitatory in nature (i.e. there was an increase in RR,
HR, BP and SC, and a decrease in ST following spinal mobilization,
compared to controls and placebo intervention), indicating sym-
3.2. Study characteristics
pathetic up-regulation in both the healthy and symptomatic pop-
ulation. This was the same whether the mobilizations were applied
Five studies were of crossover design, on a healthy population,
to the cervical, thoracic, or lumbar spine.
that compared the intervention to both a placebo and a control
condition. Just one study was conducted on a patient population
(Sterling et al., 2001). Five of the seven studies included in this 3.4. Additional information yielded from individual studies
review applied spinal mobilization to the cervical spine (Petersen
et al., 1993; Chiu and Wright, 1996; McGuiness et al., 1997; One study Chiu and Wright (1996) compared the effects of
Vincenzino et al., 1998; Sterling et al., 2001), one to the thoracic different rates of mobilization on sympathetic outflow rather than
spine (Jowsey and Perry, 2010), and one applied the mobilisation to comparing mobilization to placebo and control. These authors
the lumbar spine (Perry and Green, 2008). All studies measured found that a higher rate of mobilization (2 Hz) led to significant
changes in sympathetic output during and/or immediately increase in SC compared to a lower rate (0.5 Hz), and to a control
following each intervention using sympathetic outcome measures. condition. No significant differences in skin temperature were
See Table 1 for a comprehensive summary of the data extracted and identified between the two intervention groups and the control
the outcome measures used. group.
One study Perry and Green (2008) found that a unilaterally
applied posterior-anterior mobilisation at 2 Hz to the left L4/5
3.3. Synthesis of results
zygopophyseal joint results in side-specific peripheral SNS changes
(increase in skin conductance) in the lower limbs compared to
All studies ranked high on the PEDro rating scale, and are
placebo and control.
detailed in Table 2. Six of the seven studies reviewed did not pro-
vide adequate explanations of allocation concealment. Therefore, a
regarding the risk of bias that this procedure might have introduced 4. Discussion
could not be reached. Furthermore, the risk of attrition bias, and
random sequence generation bias, could not be assessed from the The primary aim of this review was to evaluate the literature
information provided, in five and four of the studies respectively. pertaining to the effects of spinal mobilizations on SNS outcome
Refer to Table 3 for a breakdown of the RoB judgements. measures, in both healthy and symptomatic populations, irre-
Primary data was not available to complete a meta-analysis; one spective of segmental level. The second aim was to establish the
corresponding author replied to say the data was no longer avail- level of evidence for a change in sympathetic outcome measures.
able and the other corresponding author did not respond to the Each of the high-quality RCTs included in this review established
email. Overall, best-evidence synthesis indicated that there was a statistically significant change, consistent with sympathetic
strong evidence for statistically significant changes in SC, RR, HR, excitation, in a variety of sympathetic outcome measures. These
and BP among the healthy population, following spinal mobi- changes were observed following spinal mobilizations, and were
lisation (Petersen et al., 1993; McGuiness et al., 1997; Vicenzino compared to placebo and/or control interventions. Therefore, there

Table 3
Risk of bias judgements.

Authors Risk of bias

Random sequence Allocation Performance Detection Attrition Reporting Other

generation bias concealment bias bias bias bias bias bias

Petersen et al., 1993 L ? L ? ? L L

Chiu and Wright 1996 ? ? L L ? L L
McGuiness et al., 1997 ? ? L L ? L L
Vicenzino et al., 1998 ? ? L L ? L L
Sterling et al., 2001 L ? L L ? L L
Perry and Green 2008 L L L L L L L
Jowsey and Perry 2010 ? ? L L L L L

L ¼ Low risk bias, ? ¼ Unclear risk bias, H ¼ High risk bias.

L. Kingston et al. / Manual Therapy 19 (2014) 281e287 285

is compelling evidence that spinal mobilizations result in an in- stimulation of sympathetic fibres through spinal mobilizations
crease in sympathetic activity, irrespective of the segment mobi- (Sterling et al., 2001; Evans, 2002), as a legitimate source of
lized. In contrast to the findings of the current review, a recent sympathetic excitation. After all, the sympathetic chain and
study (Welch and Boone, 2008) investigated the sympathetic accompanying ganglia, extend from the upper cervical vertebrae
response of the cervical and thoracic spine, following HVLA thrust down to the coccyx (Palastanga et al., 2006). A mobilization to a
manipulations on forty volunteers. Manipulations of cervical spine vertebral body in any region of the spine could stimulate local
in Welch and Boone’s (2008) study resulted in a sympathetic sympathetic fibres, side specific responses identified in two
inhibitory response; while manipulations of the thoracic spine studies (Perry and Green, 2008; Jowsey and Perry, 2010) provides
elicited a sympathetic excitatory response. The authors concluded some support for this idea.
that the results provided evidence for a segmental bias. However, Finally, there is some speculation that joint oscillation may
this review found a consistent trend towards sympathetic excita- stimulate spinal reflex pathways (Dishman and Bulbulian, 2000;
tion, irrespective of the region of the spine that received the Jowsey and Perry, 2010). Interestingly, the application of an oscil-
mobilization. This may represent a different response of the SNS to latory technique is common to all studies in this review. In each
spinal mobilizations compared to HVLA thrust manipulations. study, the oscillatory technique resulted in statistically significant
However, the authors feel that this is unlikely, due to insufficient changes in sympathetic outcomes compared to a placebo and/or
reporting on the study by Welch and Boone (2008), which means control. Further to this, recent research (Moulson and Watson,
that the study cannot be repeated. Overall there seems to be poor 2006; Moutzouri et al., 2012) that investigated the effects of a
support from high-quality RCTs for the theory of a segmental bias. sustained glide applied to C5/6 and L4, respectively, demonstrated
This review revealed convincing evidence that the sympathetic no significant change to SC between intervention and control
response to spinal mobilizations is excitatory in nature, irrespective conditions, during the treatment period. Thus supporting the the-
of the level of the spine mobilized. ory that it is the oscillatory component of the technique that is
central to generating the response observed (Jowsey and Perry,
4.1. Context of this research 2010).

Undoubtedly, the current findings are of significant interest to 4.2. Limitations of this review
all manual therapists. The studies included in this review provide
compelling evidence that spinal mobilizations elicit sympathetic One of the main limitations in scoring the studies for this review
excitation. To establish the clinical relevance of these findings was the inflexibility of the PEDro rating criteria. All studies were
they will be examined in the context of pain modulating systematically under-rated for criteria numbers six and nine of the
theories. PEDro rating scale. These criteria pertain to blinding of the therapist
Sympathetic excitation and concurrent hypoalgesia is postu- and either an intention to treat analysis or explicit confirmation
lated to be mediated via the dPAG in humans (Sterling et al., 2001; that all participants received conditions as allocated. The design of
Evans, 2002), through neural descending pathways. It is speculated these studies did not permit blinding of the therapists. The SNS
that mobilization of a spinal segment stimulates receptors present responses are automatic in nature, and were electronically
in joints, capsules, tendons and connective tissues, which are measured in each study. Whether or not blinding of the therapist or
capable of directly or indirectly activating dPAG mechanisms the assessor could affect the internal validity in this instance is
(Pickar, 2002; Schmid et al., 2008). Results from studies in this debatable.
systematic review have consistently demonstrated increases in Five of the seven high quality trials applied spinal mobiliza-
sympathetic activity, such as HR and SC, together with diminished tions to the cervical spine (Petersen et al., 1993; Chiu and Wright,
pressure-pain thresholds and improved motor function (Petersen 1996; McGuiness et al., 1997; Vicenzino et al., 1998; Sterling et al.,
et al., 1993; McGuiness et al., 1997; Vicenzino et al., 1998; Sterling 2001), therefore only two studies (Perry and Green, 2008; Jowsey
et al., 2001) consistent with dPAG-mediated effects (Kuraishi and Perry, 2010) in this review contributed to the finding about
et al., 1991; Wright, 1995). an overall excitatory response regardless of the level of the spine.
Another indicator of a multi-system response identified by Only one study (Sterling et al., 2001) investigated changes in
studies in this review is peripheral vasoconstriction. This is sympathetic outcome measures in a symptomatic population,
demonstrated by a significant increase in BP (McGuiness et al., diluting the level of evidence that could be established for this
1997; Vicenzino et al., 1998) together with a significant sub-group.
decrease in the skin temperature of peripheral limbs (Petersen Another limitation of this review is that only English language
et al., 1993; Chiu and Wright, 1996; Sterling et al., 2001). Pe- studies were included. There is evidence that English language
ripheral vascular control, which directly influences BP, is modu- studies are more likely to be positive therefore potentially
lated by the dPAG (Carrive, 1993). Considering the above introducing a language bias (Egger et al., 1997). Also studies were
observations, it could be assumed that sympatho-excitation is a restricted to those in published format. Publication bias may
centrally evoked response, likely to be modulated at least in part, have been introduced. There is evidence to suggest that pub-
through dPAG pathways. lished studies are more likely to be positive (Easterbrook et al.,
It is hypothesized that direct stimulation of the sympathetic 1991).
ganglia by mobilization of the vertebrae, is a possible mechanism
for the sympathetic response (Evans, 2002). The middle and 4.3. Clinical implications and future research
inferior cervical ganglia, which are adjacent to C6 and C7
respectively, have postganglionic axons that project to the heart Studies considered in this review have shown there could be
(Schmid et al., 2008). A number of authors in this review (Petersen potential to treat distal pain, more proximally. This is due to the
et al., 1993; Chiu and Wright, 1996; McGuiness et al., 1997; connection between sympathetic excitation and pain modulation,
Vicenzino et al., 1998; Sterling et al., 2001) applied spinal mobi- as discussed in the literature (Petersen et al., 1993; Sterling et al.,
lizations to the level of C5/6, potentially activating the adjacent 2001; Pickar, 2002). In instances of acute injury, or in the pres-
ganglia, which may account for the increase in HR observed ence of painful inflammation of the target area, it would be useful
(Schmid et al., 2008). Many authors have cited the potential to treat centrally, away from the target area. According to the
286 L. Kingston et al. / Manual Therapy 19 (2014) 281e287

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