Discogenic pain = Central Sensitization

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Self-reported pain severity, quality of life,
disability, anxiety and depression in patients
classified with 'nociceptive', 'peripheral
neuropathic' and 'central sensitisation' pai...
Article in Manual therapy · November 2011
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2. Original article
Self-reported pain severity, quality of life, disability, anxiety and depression in
patients classified with ‘nociceptive’, ‘peripheral neuropathic’ and ‘central
sensitisation’ pain. The discriminant validity of mechanisms-based classifications
of low back (Æleg) pain
Keith M. Smart a,*, Catherine Blake b
, Anthony Staines c
, Catherine Doody b
a
St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland
b
UCD School of Public Health, Physiotherapy and Population Science, University College Dublin, Belfield, Dublin 4, Ireland
c
Health Systems Research, School of Nursing, Dublin City University, Dublin 9, Ireland
a r t i c l e i n f o
Article history:
Received 26 July 2011
Received in revised form
2 October 2011
Accepted 11 October 2011
Keywords:
Nociceptive pain
Peripheral neuropathic pain
Central sensitisation
Discriminant validity
Classification
a b s t r a c t
Evidence of validity is required to support the use of mechanisms-based classifications of pain clinically.
The purpose of this study was to evaluate the discriminant validity of ‘nociceptive’ (NP), ‘peripheral
neuropathic’ (PNP) and ‘central sensitisation’ (CSP) as mechanisms-based classifications of pain in
patients with low back (Æleg) pain by evaluating the extent to which patients classified in this way differ
from one another according to health measures associated with various dimensions of pain.
This study employed a cross-sectional, between-subjects design. Four hundred and sixty-four patients
with low back (Æleg) pain were assessed using a standardised assessment protocol. Clinicians classified
each patient’s pain using a mechanisms-based classification approach. Patients completed a number of
self-report measures associated with pain severity, health-related quality of life, functional disability,
anxiety and depression. Discriminant validity was evaluated using a multivariate analysis of variance.
There was a statistically significant difference between pain classifications on the combined self-report
measures, (p ¼ .001; Pillai’s Trace ¼ .33; partial eta squared ¼ .16). Patients classified with CSP (n ¼ 106)
reported significantly more severe pain, poorer general health-related quality of life, and greater levels of
back pain-related disability, depression and anxiety compared to those classified with PNP (n ¼ 102) and
NP (n ¼ 256). A similar pattern was found in patients with PNP compared to NP.
Mechanisms-based pain classifications may reflect meaningful differences in attributes underlying the
multidimensionality of pain. Further studies are required to evaluate the construct and criterion validity
of mechanisms-based classifications of musculoskeletal pain.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
Mechanisms-based pain classification refers to the classification
of clinical presentations of pain based on assumptions as to the
underlying neurophysiological mechanisms responsible for its
generation and/or maintenance (Woolf et al., 1998). Mechanisms-
based classifications have been advocated clinically on the
grounds that they may help to i) explain the variety and complexity
of clinical presentations of pain and ii) improve clinical outcomes
by facilitating the selection of treatments either known or
hypothesised to target the dominant neurobiological mechanisms
underlying patients’ pain (Smart et al., 2008; Scholz et al., 2009).
Nociceptive pain (NP), peripheral neuropathic pain (PNP) and
central sensitisation pain (CSP) have been proposed as clinically
meaningful mechanisms-based classifications of musculoskeletal
pain (Butler, 2000; Lidbeck, 2002; Woolf, 2004; Yunus, 2005).
‘Nociceptive’ pain refers to pain arising predominantly from
somatic tissues in response to noxious chemical (inflammatory),
thermal or mechanical stimuli, as might occur in response to
inflammation of traumatic, degenerative or systemic origin or
ischemia secondary to mechanical loading. PNP refers to pain
arising from dysfunction of or a lesion within peripheral neural
tissue (i.e. distal to and including the dorsal root ganglion), such as
compressive neuropathies of spinal nerve roots which may induce
pathophysiological changes that lead to neuronal hyper-excitability
* Corresponding author. Tel.: þ353 1 221 4467; fax: þ353 1 221 4001.
E-mail address: k.smart@svuh.ie (K.M. Smart).
Contents lists available at SciVerse ScienceDirect
Manual Therapy
journal homepage: www.elsevier.com/math
1356-689X/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.math.2011.10.002
Manual Therapy 17 (2012) 119e125

3. and/or acquired chemical or mechanical sensitivities. And CSP
refers to pain that arises or persists as a result of aberrant pro-
cessing and/or hypersensitivity within the diffuse neural networks
of the central nervous system (CNS) engaged in nociception, in the
absence of or disproportionate to somatic tissue or peripheral nerve
pathology (Costigan et al., 2009). Key pathophysiological features
include enhanced CNS synaptic efficacy, loss of spinal inhibitory
inter-neurones, descending facilitation and altered cortical pro-
cessing (Latremoliere and Woolf, 2009).
In the mechanisms-based approach it is suggested that clinical
presentations of pain may be characterised by a dominance of one
category of pain mechanisms relative to another (Bennett et al.,
2006). A recent discriminative validity study has suggested that
NP, PNP and CSP might be distinguishable from one another clini-
cally on the basis of clusters of symptoms and signs (Smart et al.,
2011). And a preliminary reliability study has suggested that such
mechanisms-based classifications may be undertaken reliably
(Smart et al., 2010a).
However, additional forms of construct (e.g. discriminant) and
criterion (e.g. predictive, prescriptive) validity evidence are
required before a classification system can be recommended for use
in clinical practice (Streiner and Norman, 2003). Discriminant val-
idity refers to the extent to which the categories of a classification
system can be distinguished from one another on the basis of their
relationships with variables measuring the same or related
constructs (Ford et al., 2007). In light of this requirement, the
purpose of this study was to evaluate the discriminant validity of
NP, PNP and CSP as mechanisms-based classifications of pain in
patients with low back (Æleg) pain by evaluating the extent to
which patients classified with NP, PNP and CSP differ from one
another on the basis of their relationships with variables measuring
multiple dimensions of patients’ pain experiences, such as self-
reported pain severity, health-related quality of life (HRQoL),
functional disability, anxiety and depression.
It was hypothesised that patients with low back (Æleg) pain
classified with a dominance of CSP would report more severe pain,
poorer HRQoL and greater levels of low back pain-related disability,
anxiety and depression than those classified with a dominance of
PNP and NP. It was also hypothesised that a similar pattern of
differences would exist for those classified with a dominance of
PNP compared to NP.
2. Materials and methods
2.1. Study design
This study employed a cross-sectional, between-subjects design.
2.2. Setting
This multicentre discriminant validity study took place in four
hospitals, three in Ireland and one in the United Kingdom, and two
Irish-based private physiotherapy practices (Smart et al., 2011).
Ethical approval was granted by each Irish institution and the
National Research Ethics Service (UK). Data was collected between
March 2008 and September 2009.
2.3. Participants
Fifteen physiotherapists facilitated data collection, including 13
public hospital-based clinicians, one of whom was the primary
investigator (KMS), and two private practitioners.
Patients of 18 years of age or older referred with low back (Æleg)
pain were eligible for inclusion. Exclusion criteria included patients
with a history of diabetes or central nervous system injury, preg-
nancy or non-musculoskeletal low back pain. Patients were
recruited from the outpatient waiting lists of each back pain
screening clinic/physiotherapy service. All patients gave signed
informed consent prior to their participation. A flowchart detailing
patient recruitment is presented in Fig. 1.
2.4. Instrumentation and procedures
Patient demographics were collected using a standardised data
collection sheet. Participating patients were asked to complete
a number of self-report questionnaires relevant to the multidi-
mensionality of pain in accordance with recommendations in the
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5=nniapcicaroht/lacivreC
4=nPBLlateleksolucsum-noN
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)8=ntnesnoc-noN(
005=nelbigilelatoT
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niapevitpecicoN
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201=nniap
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601=nniap
/dexim(dedulcxelatoT
)niapetanimretedni
63=n
11=nPNP/PN
71=nPSC/PN
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2=nPSC/PNP/PN
1=netanimretednI
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502=nHCNMA
671=nHUVS
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7=nPP
Fig. 1. Flowchart of patient recruitment. Abbreviations: AMNCH: Adelaide and Meath, incorporating the National Children’s Hospital, SVUH: St Vincent’s University Hospital, GST:
Guy’s and St Thomas’ NHS Foundation Trust, WRH: Waterford Regional Hospital, PP: Private Practice. NP-Nociceptive pain, PNP-Peripheral neuropathic pain, CSP-Central sensi-
tisation pain.
K.M. Smart et al. / Manual Therapy 17 (2012) 119e125120

4. pain and low back pain literature (Bombardier, 2000; Turk et al.,
2003; Dworkin et al., 2005).
Specifically, a number of self-report parameters related to the
severity, physical functioning and affective dimensions of pain were
measured. Physical and mental HRQoL was measured using the SF-
36 Health Survey (version 2, standard 4 week recall) (Medical
Outcomes Trust, Massachusetts). The SF-36 Health Survey is reli-
able and valid, and its results can be compared and contrasted
across studies and patient populations (Ware, 2000).
Back pain-related disability was assessed using the Roland
Morris Disability Questionnaire (RMDQ). Scores range from ‘0’ (no
disability) to ‘24’ (maximum disability). The RMDQ is short, simple
to complete and is considered to be reliable and valid (Roland and
Fairbank, 2000).
The Hospital Anxietyand Depression Scale (HADS) (Zigmund and
Snaith, 1983) was used to evaluate emotional health. The HADS has
a minimum and maximum score range for anxiety (HADS-A) and
depression (HADS-D) of 0e21. Higher scores indicate greater pres-
ence/severity of the attribute (Snaith, 2003). It is quick to complete
with excellent psychometric properties (Haythornthwaite, 2006).
Cut-points from which to infer the presence of anxiety and
depression were defined as: 0e7 ¼ normal, 8e10 ¼ suggestive, and
!11 indicating probable presence of the mood disorder (Snaith,
2003). Grading according to severity has also been reported with
scores of 0e7, 8e10, 11e14 and 15e21 categorised as normal, mild,
moderate and severe respectively (Pande, 2004; Vignaroli et al.,
2006).
After completing the questionnaires each patient was assessed
using a standardised clinical interview and examination procedure
based on accepted clinical practice (Petty and Moore, 2001). During
the clinical interview patients were encouraged to disclose details
of their low back pain history and current symptoms as well as rate
the severity of their pain by means of an 11-point verbal numerical
rating scale (vNRS) in response to the following standardised
question:
‘If zero is ‘no pain’ and 10 is the worst pain you can imagine, how
would you rate the severity of your pain on average, in relation to
the last 24 hours?’
Numerical rating scales are easy to administer and score, and
they are reliable and valid (Von Korff et al., 2000). Cut-points for
grading the severity of low back pain were defined as follows:
4 ¼ Mild, 5e6 ¼ Moderate, ! 7 ¼ Severe (Jensen et al., 2001).
The clinical examination included postural, movement and
neurological based assessments. After completing the clinical
interview and examination clinicians classified each patient’s pain
presentation as being attributable to a dominance of NP, PNP, CSP
mechanisms or as ‘mixed’ (i.e. Mixed: NP/PNP, Mixed: NP/CSP,
Mixed: PNP/CSP, Mixed: NP/PNP/CSP), on the basis of a reference
standard of experienced clinical judgement, i.e. a non-standardised
general clinical impression of the likely dominant category of pain
mechanisms assumed to underlie each patient’s pain. In the
absence of a ‘diagnostic’ gold standard upon which to base such
mechanisms-based pain classifications, clinical judgement may
serve as an appropriate alternative reference standard (Katz et al.,
2000; Streiner and Norman, 2003). For the purpose of this study
clinicians were provided with mechanisms-based classifications of
pain that were operationally defined in the following way; NP: pain
predominantly associated with the activation of the peripheral
receptive terminals of primary afferent neurones in response to
noxious chemical (inflammatory), mechanical or thermal stimuli;
PNP: pain initiated or caused by a primary lesion or dysfunction in
the peripheral nervous system; CSP: pain initiated or caused
primarily by dysfunction in the central nervous system (Smart
et al., 2010b).
2.5. Data analysis
Univariate analyses tested for differences in gender and age
across classifications. Discriminant validity was evaluated using
a multivariate analysis of variance (MANOVA) in order to investi-
gate differences in self-report measures across pain classifications.
A Bonferroni correction was applied to adjust p-value thresholds to
account for multiple comparisons. Data were analysed with SPSS
for windows, version 15 (SPSS Inc, Chicago, IL).
3. Results
A convenience sample of 551 patients with musculoskeletal low
back (Æleg) pain disorders were invited to participate in this study.
Fifty-one ineligible patients, and 36 patients with a mixed (n ¼ 35)
or indeterminate (n ¼ 1) pain state were excluded. Patients clas-
sified with mixed pain (i.e. relatively equal contribution of pain
mechanisms) were excluded so as to retain only those judged to
have a pain presentation attributable to a dominant category of
pain mechanisms. Patient demographics for the final sample
(n ¼ 464) are presented in Table 1. Two hundred and fifty-six (55%)
patients were classified with a dominance of NP, 102 (22%) with
PNP and 106 (23%) with CSP. There were no statistically significant
differences in the gender (c2
(2, n ¼ 464) ¼ 1.59, p ¼ .45 Cramer’s
V ¼ .06) and age (ANOVA ¼ Browne-Forsythe F-ratio .23 (df 2, 463),
p ¼ .80) of patients across pain classifications. Mean questionnaire
scores across pain classifications are shown in Table 2
There was a statistically significant difference between pain
classifications on the combined dependent variables, F (12,
802) ¼ 13.00, p ¼ .001; Pillai’s Trace ¼ .33; partial eta squared ¼ .16.
When the results for the dependent variables were considered
separately there were statistically significant differences, using
a Bonferroni adjusted alpha level of p ¼ .008, between pain clas-
sifications in relation to pain severity, physical and mental HRQoL,
back pain-related disability, and levels of anxiety and depression.
The F-ratio, significance level and effect size for each co-variable in
the MANOVA is presented in Table 3. Effect sizes (partial eta
squared), based on guidelines reported by Cohen (1998)
(.01 ¼ small, .09 ¼ medium, .25 ¼ large), were ‘medium’ for all
self-report measures.
Post-hoc comparisons using Tukey’s Honestly Significant
Difference test (Tukey HSD) were performed in order to further
explore and identify differences in self-report measures between
each of the three pain classifications. Descriptive statistics for each
co-variable within the MANOVA upon which the post-hoc
comparisons were based, are presented in Table 4. Between-group
comparisons (mean differences, Tukey HSD significance levels, and
95% confidence intervals for mean differences) for each of the six
co-variables are presented in Table 5. Post-hoc analyses indicated
that differences in mean scores on each questionnaire were
statistically significant (p .05, range .001e.035) for all pair-wise
comparisons across mechanisms-based classifications, except for
the difference in HADS-A scores between NP and PNP (p .495).
3.1. Pain severity
Patients classified with a dominance of CSP reported more
severe pain than those with NP (mean difference 2.7, 95% CI:
2.1e3.3, p < .001) and PNP (mean difference 1.3, 95% CI: .6e2.1,
p < .001), whilst patients with PNP reported more severe pain than
those with NP (mean difference 1.4, 95% CI: .7e2.0, p < .001). The
mean vNRS scores for patients with CSP, PNP and NP were 7.2, 5.9
and 4.5, corresponding to ‘severe’, ‘moderate’ and ‘mild’ pain
respectively. Whilst it is accepted that such categorisations may be
somewhat arbitrary (Salaffi et al., 2007), these findings provide
K.M. Smart et al. / Manual Therapy 17 (2012) 119e125 121

5. some evidence that such mechanisms-based classifications may be
associated with potentially clinically meaningful categorical
distinctions in pain severity.
3.2. Physical parameters
Mean differences in questionnaire scores (SF-36 PCS, RMDQ)
were statistically significant (p < .05, range .005e.018) for all paired
comparisons. Patients classified with a dominance of NP reported
better physical HRQoL and less LBP-related disability than those
with PNP and CSP. A similar pattern was observed in a comparison
between patients with PNP and CSP.
3.3. Affective parameters
Patients classified with an assumed dominance of CSP mecha-
nisms reported poorer mental HRQoL and greater levels of anxiety
and depression than those classified with NP (p < .001) and PNP
(p < .001e.035). Patients classified with CSP had mean scores
equivalent to borderline ‘probable presence’/’moderate’ levels of
anxiety and ‘suggestive presence’/’mild’ levels of depression
according to defined cut-points (Snaith, 2003; Pande, 2004;
Vignaroli et al., 2006). The corresponding scores in patients with
both NP and PNP were equivalent to ‘normal’, suggesting a poten-
tially clinically meaningful difference in levels of anxiety and
depression in patients classified with CSP compared to those with
NP and PNP.
4. Discussion
This study evaluated the discriminant validity of NP, PNP and
CSP as mechanisms-based classifications of pain in a patient pop-
ulation with low back (Æleg) pain disorders. Patients classified with
a dominance of CSP reported more severe pain, poorer physical and
mental HRQoL, and greater levels of back pain-related disability,
depression and anxiety compared to those classified with a domi-
nance of PNP and NP. This pattern was largely repeated in
a comparison between those classified with PNP and NP. These
findings provide some evidence supporting the discriminant val-
idity of mechanisms-based classifications of low back (Æleg) pain in
clinical practice.
The findings from this study are broadly consistent with
a number of epidemiological studies which have found patients
with chronic pain of predominantly (peripheral) neuropathic origin
generally report more severe pain, poorer physical health and
greater interference with activities of daily living, and poorer
mental health compared to those with chronic pain of non-
neuropathic (i.e. nociceptive) origin (Smith et al., 2007;
Bouhassira et al., 2008; Berger et al., 2009). However, our findings
suggest that whilst the levels of self-reported anxiety and depres-
sion were higher in patients classified with PNP compared to NP
these levels equated to ‘normal’ or borderline ‘suggestive presence/
mild’, and as such may be of doubtful clinically significance. Further
studies are required to investigate the clinical significance of
emotional comorbidities in patients with low back pain disorders
and a dominance of PNP mechanisms.
Epidemiological data associated with pain states characterised
by a dominance of dysfunctional central processing is not readily
available, since central sensitisation/hyper-excitability pain is less
well defined and established as a construct and clinical entity
(Loeser and Treede, 2008; Macfarlane et al., 2009). However
syndromes widely regarded to reflect central pain dysfunction,
Table 2
Questionnaire scores by pain classification (n ¼ 464).
Variable Nociceptive
(n ¼ 256)
Peripheral
neuropathic
(n ¼ 102)
Central
sensitisation
(n ¼ 106)
vNRS (0e10)
(n ¼ 464)
4.6 (2.3, 0e10) 6.0 (2.1, 0e10) 7.3 (1.9, 1e10)
SF36 (n ¼ 428)
PCS 37.0 (8.4,
14.7e58.3)
32.8 (8.4,
14.6e54.6)
29.3 (7.4,
16.0e53.1)
MCS 45.9 (11.4,
13.0e65.4)
40.0 (14.0,
14.9e70.0)
35.2 (12.1,
11.8e65.3)
RMDQ (n ¼ 438) 8.8 (5.3, 0e23) 11.8 (5.7, 0e23) 14.5 (5.8, 1e24)
HADS-A (n ¼ 420) 6.9 (4.2, 0e21) 7.5 (4.4, 0e18) 10.6 (4.5, 2e21)
HADS-D (n ¼ 420) 4.9 (3.7, 0e17) 7.0 (4.4, 0e17) 9.5 (4.4, 1e20)
Data are presented as Mean (SD, Range). Abbreviations: vNRS-Verbal numerical
rating scale, SF36-SF36 Health Survey, version 2 (Norm-based scores), PCS-Physical
Component Summary score, MCS-Mental Component Summary score, RMDQ-
Roland Morris Disability Questionnaire, HADS-A-Hospital Anxiety and Depression
Scale-Anxiety, HADS-D-Hospital Anxiety and Depression Scale-Depression.
Table 1
Patient demographics by pain classification (n ¼ 464).
Variable Nociceptive
(n ¼ 256)
Peripheral
Neuropathi
(n ¼ 102)
Central
Neuropathic
(n ¼ 106)
Gender (Female) 150 (59%) 53 (52%) 57 (54%)
Age y, Mean (SD, Range) 44 (14.5,
19e85)
44 (13.1,
20e76)
43 (12.3,
20e80)
Source of referral
GP 144 (56%) 68 (67%) 44 (42)
Orthopaedics 41 (16%) 12 (12%) 11 (10)
ED 25 (10%) 14 (14%) 5 (5%)
Pain clinic 6 (2%) 3 (3%) 38 (36%)
Occ Health 25 (10%) 2 (2%) 2 (2%)
Rheumatologist 4 (2%) 0 1 (1%)
Other 11 (4%) 3 (3%) 5 (5%)
Assessment setting
BPSC 128 (50%) 68 (67%) 24 (23%)
Physio. Dept 119 (47%) 33 (32%) 39 (37%)
Pain Clinic 2 (1%) 1 (1%) 43 (41%)
Private Practice 7 (3%) 0 0
Predominant pain location
Back 209 (82%) 9 (9%) 65 (61%)
Back/Thigh 37 (15%) 19 (19%) 17 (16%)
Uni Leg BK 3 (1%) 60 (59%) 4 (4%)
Back/Uni leg BK 7 (3%) 11 (11%) 10 (9%)
Bilat Leg BK 0 1 (1%) 1 (1%)
Back/Bilat leg BK 0 2 (2%) 9 (9%)
Duration current episode
0e3 weeks 17 (7%) 2 (2%) 2 (2%)
4e6 weeks 33 (13%) 14 (14%) 2 (2%)
7e12 weeks 33 (13%) 18 (18%) 2 (2%)
4e6 months 36 (14%) 23 (22%) 2 (2%)
7e12 months 27 (11%) 21 (21%) 10 (9%)
> 1 year 110 (43%) 24 (23%) 88 (83%)
(mean duration (yrs),
SD, range)
(6.8, 6.9,
1e40)
(3.4, 3.3,
1e14)
(7.1, 7.2,
1.5e40)
Work status
Full time 111 (43%) 35 (34%) 12 (11%)
Part-time 23 (9%) 10 (10%) 7 (6%)
Homemaker 23 (9%) 8 (8%) 9 (9%)
Off work (2er
LBP) 33 (13%) 27 (27%) 22 (21%)
Off work (2er
Other) 13 (5%) 6 (6%) 9 (9%)
U/E 13 (5%) 2 (2%) 6 (6%)
Retired 28 (11%) 11 (11%) 9 (9%)
Student 7 (3%) 1 (1%) 2 (2%)
Reg Disabled (2er
LBP) 2 (1%) 0 28 (26%)
Reg Disabled (2er
Other) 1 (0%) 2 (2%) 1 (1%)
Unknown 0 0 1 (1%)
Medico-legal case pending 10 (4%) 3 (3%) 26 (25%)
Abbreviations: GP-General Practitioner, ED-Emergency Dept., Occ Health-
Occupational Health Dept., BPSC-Back Pain Screening Clinic, Physio. Dept-
Physiotherapy Dept., Uni Leg BK-Unilateral leg pain below knee, Bilat Leg BK-
Bilateral leg pain below knee, LBP-Low back pain, U/E-Unemployed, Reg Disabled-
Registered Disabled.
K.M. Smart et al. / Manual Therapy 17 (2012) 119e125122

6. such as fibromyalgia/chronic widespread pain (Clauw and Crofford,
2003), are characterised by significant reductions in health-related
quality of life, physical functioning and psychological wellbeing
(Cieza et al., 2004; Macfarlane et al., 2009). Also, a recent cross-
sectional study found higher levels of anxiety and depression and
poorer HRQoL in patients with chronic fibromyalgia compared to
neuropathic pain of mixed aetiologies (Gormsen et al., 2010). Our
findings are consistent with these assertions.
The mechanisms underlying associations between pain severity,
general, physical and mental health and chronic pain are not well
understood (Feuerstein and Beattie, 1995; Dersch et al., 2002). We
speculate that differences in the severity of pain reported by
patients classified with NP, PNP and CSP could reflect differences in
the neurophysiological mechanisms underlying each category of
pain. For example, the higher levels of pain reported by patients
classified with a dominance of CSP could reflect alterations in the
chemical and structural, and therefore functional, properties of CNS
circuits associated with central sensitisation. Sensitisation of wide
dynamic range neurons in the dorsal horn of the spinal cord, loss of
spinal or supraspinal inhibitory mechanisms, descending facilita-
tion or altered cortical processing of nociceptive inputs could all
contribute to augmented nociception, pain hypersensitivity and
ultimately a heightened pain experience (Craig, 2006; Fields et al.,
2006; Latremoliere and Woolf, 2009). Similarly, trauma, compres-
sion, inflammation or ischemia associated with entrapment
neuropathies of spinal roots or dorsal root ganglia could induce
a cascade of pathophysiological processes, including ectopic
impulse generation, cross-excitation, altered synaptic efficacy and
neuroimmune interactions (Devor, 2006; Scadding and
Koltzenberg, 2006; Costigan et al., 2009), the net effect of which
could lead to an overall increase in excitatory drive and more severe
pain in patients with a dominance of PNP compared to NP (Hökfelt
et al., 2006).
Further speculation concerning the relative presence or absence
of cognitive-affective pain mediating mechanisms might account
for the differences in levels of self-reported emotional wellbeing
and physical function in patients classified with a dominance of NP,
PNP and CSP. For example, forebrain-mediated processes evoked in
response to painful stimuli could be responsible for the generation
of concomitant affective states such as anxiety and depression in
patients whose pain may be attributable to a dominance of central
mechanisms (Neugebauer et al., 2009). In addition, maladaptive
cognitive appraisals, possibly linked to disease conviction, fear of
pain and its avoidance, could adversely influence and distort
patients’ perceptions regarding their functional capabilities and
therefore self-reports of functional disability (Feuerstein and
Beattie, 1995). However, the factors that determine if or to what
extent such forebrain processes or maladaptive cognitive appraisals
ensue after a pain event, i.e. why some patients but not others have
low back pain in association with anxiety, depression and func-
tional disability, are not yet known.
The findings from this study, which suggest mechanisms-based
classifications of pain such as NP, PNP and CSP may reflect
significant differences in attributes underlying the multidimen-
sionality of pain, could have important implications for clinical
practice. For example, the identification of patients with a domi-
nance of central sensitisation/hyper-excitability may alert clinicians
to the need for more detailed clinical assessments and possible
management of pain-related comorbidities such as anxiety,
depression and disability.
In addition, mechanisms-based classifications of pain may
provide clinicians with insight into the prognosis for a patient’s
recovery. The findings from this study suggest that patients clas-
sified with a dominance of central pain/hyper-excitability may
present with more severe pain and higher levels of anxiety,
depression and functional disability; factors that might be consid-
ered as negative prognostic indicators in light of evidence sug-
gesting that such factors may be important predictors of poorer
recovery from episodes of and interventions for low back pain
(Celestin et al., 2009; Hancock et al., 2009; Chou and Shekelle,
2010). Similarly, poorer HRQoL has been identified as a potential
negative prognostic indicator in patients with neuropathic pain
(Otto et al., 2007).
Whilst there is some limited face validity evidence to suggest
that mechanisms-based pain classification may inform clinical
decision-making related to the assessment, prognosis and treat-
ment of patients’ pain (Smart and Doody, 2006) more robust val-
idity evidence from suitably designed clinical studies is required to
further evaluate the predictive and prescriptive validity of
mechanisms-based classifications of pain.
The findings from this study should be interpreted in light of
a number of limitations. Whilst categorical differences in pain
severity, anxiety and depression were identified between classifi-
cations, the actual clinical significance of these differences (e.g.
a mean difference in vNRS for pain severity in patients classified
with a dominance of CP versus PNP ¼ 1.3) remains debatable.
The discriminant validity of mechanisms-based classifications of
musculoskeletal pain in this study was evaluated using a limited
number of self-report measures associated with the multidimen-
sionality of pain. The influence of other factors such as occupational
status and medico-legal conflict were not assessed but could be
Table 3
MANOVA-derived co-variable test statistics.
F-ratio (degrees
of freedom)
Bonferroni adjusted
significance level
(p .008)
Effect size
(Partial eta
squared
vNRS 55.0 (2, 405) .001 .21
SF-36 PCS 30.7 (2, 405) .001 .13
SF-36 MCS 28.2 (2, 405) .001 .12
RMDQ 37.5 (2, 405) .001 .16
HADS-A 25.6 (2, 405) .001 .11
HADS-D 42.7 (2, 405) .001 .18
Table 4
MANOVA-derived descriptive statistics (n ¼ 408).
Pain Classification Mean Std. Deviation N
vNRS (pain intensity) 1 Nociceptive 4.505 2.2692 222
2 Peripheral Neuropathic 5.857 2.1347 91
3 Central Neuropathic 7.211 1.8502 95
SF-36 PCS 1 Nociceptive 36.927 8.4033 222
2 Peripheral Neuropathic 32.622 8.3544 91
3 Central Neuropathic 29.336 7.5160 95
SF-36 MCS 1 Nociceptive 46.268 11.1757 222
2 Peripheral Neuropathic 40.045 13.8701 91
3 Central Neuropathic 35.660 11.9870 95
RMDQ 1 Nociceptive 8.72 5.356 222
2 Peripheral Neuropathic 11.90 5.739 91
3 Central Neuropathic 14.40 5.775 95
HADS-A 1 Nociceptive 6.90 4.263 222
2 Peripheral Neuropathic 7.51 4.423 91
3 Central Neuropathic 10.65 4.380 95
HADS-D 1 Nociceptive 4.95 3.747 222
2 Peripheral Neuropathic 7.00 4.420 91
3 Central Neuropathic 9.49 4.405 95
Abbreviations: vNRS-verbal Numerical rating scale for pain severity, SF-36 PCS-
Physical Component Summary score form the SF-36 Health Survey, SF-36 MCS-
Mental Component Summary score form the SF-36 Health Survey, RMDQ-Roland
Morris Disability Questionnaire, HADS-A-Hospital Anxiety and Depression Scale-
Anxiety score, HADS-D-Hospital Anxiety and Depression Scale-Depression score.
K.M. Smart et al. / Manual Therapy 17 (2012) 119e125 123

7. relevant. Functional performance measures, quantitative sensory
testing profiles or functional magnetic resonance imaging could be
employed as additional methods with which to evaluate the
discriminant validity of mechanisms-based classifications of
musculoskeletal pain. Classification systems require the accumu-
lation of validity evidence in order to support their use in clinical
practice.
Differences in measures of pain-related constructs between
each category of pain were found for a relatively large and repre-
sentative patient population with low back pain disorders based in
geographical areas within Ireland and the United Kingdom. Addi-
tional studies are required to ascertain whether or not these find-
ings generalise to broader patient populations with other
musculoskeletal pain conditions sampled from wider geographical
locations.
5. Conclusion
This study suggests that mechanisms-based classifications of
pain such as NP, PNP and CSP may be associated with potentially
clinically meaningful differences in physical and emotional well-
being, as measured by a number of self-report instruments. We
speculate that various neurobiological mechanisms may account
for some of these differences. Mechanisms-based classifications of
pain may be useful for informing subsequent clinical decision-
making surrounding the assessment, prognosis and treatment of
patients’ pain. However, further studies evaluating the predictive
and prescriptive validity of mechanisms-based classifications of
pain are required to substantiate this assertion.
Conflicts of interest
None declared.
Acknowledgements
This research was funded by the Health Research Board (of
Ireland) (Grant No. CTPF-06-17). The author wishes to thank the
following chartered physiotherapists for their help with data
collection: Mary Cassells, Antoinette Curley, Sheila Horan (Adelaide
and Meath Hospital, Dublin), Susan Murphy, Caoimhe Harrington
(Waterford Regional Hospital, Waterford), Aoife Caffrey, Martina
Fitzpatrick (St Vincent’s University Hospital, Dublin), Russell
Mayne, Sarah Friel, Nick Spahr, Melissa Johnson, Christian van der
Merwe (St Thomas’ Hospitals NHS Foundation Trust, London)
Niamh Maloney (Milltown Physiotherapy Clinic, Dublin) and
Catherine Cradock (Portobello Physiotherapy Clinic, Dublin).
Table 5
MANOVA-derived between group comparisons.
(I) Pain classification (J) Pain classification Mean difference (I-J) Std. Error Sig. 95% Confidence Interval
Lower Bound Upper Bound
vNRS pain intensity 1 Nociceptive 2 Peripheral Neuropathic À1.353* .2675 .001 À1.982 À.723
3 Central Neuropathic À2.706* .2634 .001 À3.326 À2.086
2 Peripheral Neuropathic 1 Nociceptive 1.353* .2675 .001 .723 1.982
3 Central Neuropathic À1.353* .3152 .001 À2.095 À.612
3 Central Neuropathic 1 Nociceptive 2.706* .2634 .001 2.086 3.326
2 Peripheral Neuropathic 1.353* .3152 .001 .612 2.095
SF-36 PCS 1 Nociceptive 2 Peripheral Neuropathic 4.305* 1.0200 .000 1.906 6.705
3 Central Neuropathic 7.591* 1.0047 .001 5.228 9.955
2 Peripheral Neuropathic 1 Nociceptive À4.305* 1.0200 .001 À6.705 À1.906
3 Central Neuropathic 3.286* 1.2020 .018 .459 6.114
3 Central Neuropathic 1 Nociceptive À7.591* 1.0047 .001 À9.955 À5.228
2 Peripheral Neuropathic À3.286* 1.2020 .018 À6.114 À.459
SF-36 MCS 1 Nociceptive 2 Peripheral Neuropathic 6.223* 1.4950 .001 2.706 9.740
3 Central Neuropathic 10.608* 1.4725 .001 7.144 14.072
2 Peripheral Neuropathic 1 Nociceptive À6.223* 1.4950 .001 À9.740 À2.706
3 Central Neuropathic 4.385* 1.7617 .035 .241 8.529
3 Central Neuropathic 1 Nociceptive À10.608* 1.4725 .001 À14.072 À7.144
2 Peripheral Neuropathic À4.385* 1.7617 .035 À8.529 À.241
RMDQ 1 Nociceptive 2 Peripheral Neuropathic À3.18* .690 .001 À4.81 À1.56
3 Central Neuropathic À5.68* .679 .001 À7.28 À4.09
2 Peripheral Neuropathic 1 Nociceptive 3.18* .690 .001 1.56 4.81
3 Central Neuropathic À2.50* .813 .006 À4.41 À.59
3 Central Neuropathic 1 Nociceptive 5.68* .679 .001 4.09 7.28
2 Peripheral Neuropathic 2.50* .813 .006 .59 4.41
HADS-A 1 Nociceptive 2 Peripheral Neuropathic À.61 .539 .495 À1.88 .66
3 Central Neuropathic À3.76* .530 .001 À5.00 À2.51
2 Peripheral Neuropathic 1 Nociceptive .61 .539 .495 À.66 1.88
3 Central Neuropathic À3.15* .635 .001 À4.64 À1.65
3 Central Neuropathic 1 Nociceptive 3.76* .530 .000 2.51 5.00
2 Peripheral Neuropathic 3.15* .635 .001 1.65 4.64
HADS-D 1 Nociceptive 2 Peripheral Neuropathic À2.05* .506 .001 À3.24 À.86
3 Central Neuropathic À4.55* .498 .000 À5.72 À3.38
2 Peripheral Neuropathic 1 Nociceptive 2.05* .506 .001 .86 3.24
3 Central Neuropathic À2.49* .596 .001 À3.90 À1.09
3 Central Neuropathic 1 Nociceptive 4.55* .498 .001 3.38 5.72
2 Peripheral Neuropathic 2.49* .596 .001 1.09 3.90
* The mean difference is significant at the .05 level.Abbreviations: vNRS-verbal Numerical rating scale for pain severity, SF-36 PCS-Physical Component Summary score form
the SF-36 Health Survey, SF-36 MCS-Mental Component Summary score form the SF-36 Health Survey, RMDQ-Roland Morris Disability Questionnaire, HADS-A-Hospital
Anxiety and Depression Scale-Anxiety score, HADS-D-Hospital Anxiety and Depression Scale-Depression score.
K.M. Smart et al. / Manual Therapy 17 (2012) 119e125124

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