Sensory caracteristics
- 1. Original article Sensory characteristics of chronic non-specific low back pain: A subgroup investigationq Peter O’Sullivan*, Robert Waller, Anthony Wright, Joseph Gardner, Richard Johnston, Carly Payne, Aedin Shannon, Brendan Ware, Anne Smith School of Physiotherapy & Exercise Science, Curtin University, GPO Box 1987, Perth, WA 6845, Australia a r t i c l e i n f o Article history: Received 22 May 2013 Received in revised form 6 March 2014 Accepted 14 March 2014 Keywords: Pain sensitivity Chronic non-specific low back pain Biopsychosocial Classification a b s t r a c t It has been proposed that patients with chronic non-specific low back pain (CNSLBP) can be broadly classified based on clinical features that represent either predominantly a mechanical pain (MP) or non-mechanical pain (NMP) profile. The aim of this study was to establish if patients with CNSLBP who report features of NMP demonstrate differences in pain thresholds compared to those who report MP char-acteristics and pain-free controls. This study was a cross-sectional design investigating whether pressure pain threshold (PPT) and/or cold pain threshold (CPT) at three anatomical locations differed between patients with mechanical CNSLBP (n ¼ 17) versus non-mechanical CNSLBP (n ¼ 19 and healthy controls (n ¼ 19) whilst controlling for confounders. The results of this study provide evidence of increased CPT at the wrist in the NMP profile group compared to both the MP profile and control subjects, when con-trolling for gender, sleep and depression (NMP versus MP group Odds Ratio (OR): 18.4, 95% confidence interval (CI): 2.5e133.1, p ¼ 0.004). There was no evidence of lowered PPT at any site after adjustment for confounding factors. Those with an MP profile had similar pain thresholds to pain-free controls, whereas the NMP profile group demonstrated elevated CPT’s consistent with central amplification of pain. These findings may represent different pain mechanisms associated with these patient profiles and may have implications for targeted management. 2014 Elsevier Ltd. All rights reserved. 1. Introduction Patients with chronic non-specific low back pain (CNSLBP) pose a complex diagnostic and management challenge. Classification systems (CS) that identify mechanisms that underlie the pain dis-order have been advocated in clinical practice in order to better target interventions (O’Sullivan, 2012a, 2005; Woolf, 2011). The Quebec Task Force CS (Spitzer, 1987) whilst differentiating specific pathology and radicular pain from CNSLBP, does not further differentiate subjects with CNSLBP (Dankaerts et al., 2006). A recent review of clinical CS’s for CNSLBP concluded that a limitation of the majority of CS’s is that they do not consider underlying pain mechanisms and focus largely on biomechanical assessment (Karayannis et al., 2012). A multidimensional CS system for LBP has been proposed that at the first level triages people with LBP to identify red flag disorders and specific pathology from non-specific LBP (Fig. 1). Once identi-fied, CNSLBP disorders are further differentiated on the basis of their pain characteristic’s reflecting a spectrum from either ‘me-chanical pain’ (MP) to ‘non-mechanical pain’ (NMP) (Fig. 1). This is based on routine clinical examination of the patient’s reported pain characteristics linked to aggravating and easing factors and pain responses to movement and loading tests (O’Sullivan, 2005, 2012b; Vibe Fersum et al., 2009, 2012). While it is acknowledged that for some patients there may be a mixed pain profile for others the clinical distinction is clear. It is postulated that these groups may have different underlying neurophysiological mechanisms, where pain in the MP group is related to processes of peripheral sensiti-sation and some degree of activity dependent central sensitisation, whereas pain in the NMP group is related to more extensive changes in central pain processing. Other dimensions such as pain type, psychosocial, lifestyle, and movement related factors as well as pain comorbidities are also considered in the CS (O’Sullivan, 2005, 2012b; Vibe Fersum et al., 2009). Although this CS has pre-viously been shown to have good inter-rater reliability for identi-fication of aspects of the CS related to movement and psychological profiles (Vibe Fersum et al., 2009), no pain sensitivity (PS) testing q Ethical approval for this study was granted by the Curtin University Human Research Ethics Committee (PT0180). * Corresponding author. Tel.: þ61 8 9266 3629; fax: þ61 8 9266 3699. E-mail address: p.osullivan@curtin.edu.au (P. O’Sullivan). Contents lists available at ScienceDirect Manual Therapy journal homepage: www.elsevier.com/math http://dx.doi.org/10.1016/j.math.2014.03.006 1356-689X/ 2014 Elsevier Ltd. All rights reserved. Manual Therapy 19 (2014) 311e318
- 2. P. O’Sullivan 312 et al. / Manual Therapy 19 (2014) 311e318 Fig. 1. Multidimensional classification of LBP disorders adapted from O’Sullivan, 2005, 2012b; Vibe Fersum et al., 2009, 2012. has been conducted to quantify the sensory profiles associated with these pain characteristic profiles. Both cold hyperalgesia and widespread pressure hyperalgesia are believed to be indicative of central hyperexcitability (Woolf, 2011). Pain Sensitivity testing is used to assess sensory pre-sentations in various pain disorders (Rolke et al., 2006a) however little research has investigated PS in CNSLBP disorders and con-troversy exists regarding its value in understanding these disorders (Hubsher et al., 2013). A recent narrative review of available liter-ature in CLBP concluded that currently the available research demonstrates mixed results, with some studies documenting reduced pain thresholds suggestive of widespread or extra-segmental hyperalgesia, other studies observe only segmental hyperalgesia and others reporting no hyperalgesia at all (Roussel et al., 2013). Another recent systematic review investigating the relationship between pain thresholds and pain intensity and disability levels in LBP and neck pain patients, concluded that pain thresholds are a poor marker for patients pain and disability levels (Hubsher et al., 2013). The apparent conflict between these findings may reflect the heterogeneity of subjects in the different studies, with the potential for different pain phenotypes in the CNSCLP population unaccounted for by study design (Giesecke et al., 2004; Roussel et al., 2013). Both sensory perception and sensory testing are potentially influenced by a number of factors other than pain, such as gender, age, genetics, body composition, sleep and psychosocial factors (Dunn, 1997; O’Sullivan et al., 2008; Leboeuf-Yde et al., 2009; Heffner et al., 2011;Woolf, 2011), highlighting the need to consider these factors when conducting research into PS. While there is limited research investigating whether the presence of CNSLBP is associated with PS changes independent of these factors, a recent study reported that pressure pain threshold (PPT) was most pre-dictive of CNSLBP independent of age, gender, body composition and psychological factors (Neziri et al., 2012). Therefore the primary aim of this study was to investigate whether patients with CNSLBP who report features of NMP demonstrate differences in cold pain threshold (CPT) and PPT compared to those who report MP char-acteristics and pain-free controls.
- 3. 2. Materials and methods 2.1. Study design A cross-sectional study design was used. 2.2. Participants P. O’Sullivan et al. / Manual Therapy 19 (2014) 311e318 313 A total of 53 participants were included in the study; 36 par-ticipants with CNSLBP (13 males and 23 females with a mean age of 40.7 (standard deviation (SD) 14.0)) were recruited from local private physiotherapy clinics in the greater Perth area, and 19 pain-free controls (8 males and 11 females with a mean age of 41.9 (SD 13.9)) recruited from the same district. Pain participants were included if they had experienced pain for a minimum of 3 months, reported pain intensity on a Visual Analogue Scale (VAS) of 3 or greater on the day of testing and LBP was their primary complaint (from T12 to gluteal fold). Control subjects were included on the basis that they had not reported LBP or any other pain disorder in the previous 6 months. Individuals were excluded if they had been diagnosed with specific spinal pathology or medical causes of low back pain, were pregnant or less than 6 months post-partum or suffered from peripheral neuropathy. In all groups, subjects were excluded if they did not perceive pressure pain below 1000 kPa during PPT testing, or they did not perceive a change in cold sensation during CPT testing. A-priori power calculation deter-mined 18 participants in each group would provide 85% power to detect pairwise differences of at least one standard deviation in mean CPT or PPT assuming a lognormal distribution, at a statistical significance level of 0.05. Ethical approval for this study was granted by the Curtin University Human Research Ethics Commit-tee (PT0180). 2.3. Participants classification The CNSLBP participants, identified following a triage process to exclude red flag and specific pathology, were divided into two groups based on clinical criteria (Fig. 1). Participants in the MP group were included on the basis of: localised and anatomically defined LBP associated with reports of specific and consistent mechanical aggravating and easing factors (LBP that was more intermittent in nature and demonstrated a proportionate pain provocation and easing response to specific postures, activities and movements). Participants in the NMP group were included on the basis of: LBP was more widespread and ill defined, LBP being more constant, non-remitting, spontaneous and where minor mechani-cal loading factors (such as simple spinal movements) resulted in exaggerated (severe) or prolonged (lasting hours) pain responses (O’Sullivan, 2005). The decision to classify was based on a combi-nation of patient report and response to routine clinical examina-tion. Pain sensitivity testing was not part of this decision making process. Recruitment of the CNSLBP participants occurred across a number of Physiotherapy practices, and consecutive patients were invited to participate if they fulfilled the inclusion criteria. Further screening was performed by RW (Musculoskeletal Physiotherapist with 23 years clinical experience) and POS (Specialist Musculo-skeletal Physiotherapist and the developer of the CS who has 25 years clinical experience) both of whom are trained in the CS to ensure the patients fitted the clinical subgroups. A total of 3 par-ticipants who agreed to participate were excluded as they failed to meet all the inclusion criteria. One was excluded due to a lack of pain response to pressure, and two had a VAS of less than 3/10 on the day of testing. 2.4. Procedures On the day of testing all participants completed two question-naires, the Pittsburgh Sleep Quality Index (PSQI) and the Depres-sion Anxiety and Stress Scale (DASS 21), which have established reliability and validity (Buysse et al., 1989; Lovibond and Lovibond, 1995) and were used as covariates to control for the potential confounding effect of poor sleep quality and stress on PS. Age,waist and hip girth were also recorded. Upon agreeing to take part in the study, participants were not asked to stop any of their regular medications. A list of current medications taken over the week prior to testing was documented. Participants with NSCLBP were also asked to complete the following to provide a clinical profile. The pain intensity level of their LBP was measured using the VAS (Huskisson, 1974), and pain areas were recorded using a body chart to provide total areas of pain using the Widespread Pain Index (Wolfe et al., 2010). The Roland Morris Disability Questionnaire (RMDQ) was used to assess functional disability levels and is valid and reliable (Roland and Morris, 1983; Roland and Fairbank, 2000). The StarT Back screening tool (SBST) was used to assess risk profile (Hill et al., 2008). The PainDETECT Questionnaire was used as a validated self-report tool to identify neuropathic pain features. It is an established questionnaire with high sensitivity and specificity (Freynhagen et al., 2006). 2.5. Sensory testing For participants with CNSLBP, the most painful side was tested. The right side was used for those where there was no pain domi-nant side and for the pain-free controls. Three test sites, the dorsal aspect of the wrist joint line, the L5/SI interspinous space and the lateral calcaneus, were tested in a standardised order and location (Jones, 2007). Each site was tested 4 times with the first test acting as familiarisation with the testing procedure (Wright et al., 1994; Lewis et al., 2010). The testing protocol was strictly followed to limit tester error (Rolke et al., 2006b). Participants were allocated to testers according to time and location of testing, tester allocation was distributed evenly between the three groups, and testers were blinded to pain group allocation. 2.6. Pressure pain thresholds PPT was defined as the moment the sensation of pressure be-comes one of pressure and pain (Jones, 2007). The PPT was tested using an algometer (Somedic AB, Sweden) with a contact area of 1 cm2 which was applied perpendicularly to the skin. The pressure increased from 0 kPa at a constant rate of 40 kPa/s until PPT or a maximum of 1000 kPa (Chien and Sterling, 2010) was reached. The standardised instructions were, “Pressure will be applied at a gradual rate. Allow the pressure to increase until it reaches a point where it first feels uncomfortable and then press the button.” Testing was performed by one of two testers (CP, BW). Prior to PPT testing, consistency for PPT measurement between testers was ensured. 2.7. Cold pain thresholds An MSA Thermal stimulator (Somedic AB, Sweden) was used to obtain the CPT. Before assessing CPT a cold detection threshold was obtained for each site to confirm the participant’s ability to detect cold (Mosek et al., 2001). Each test began at a baseline temperature of 32 C, and decreased at 1C/s until reaching CPT or the automatic minimum cut-off of 5 C (Carli et al., 2002). The standardised in-structions were, “The temperature probe will gradually get cooler.
- 4. P. O’Sullivan 314 et al. / Manual Therapy 19 (2014) 311e318 Allow the temperature to drop until it reaches a point where it first feels uncomfortably cold, and then press the button.” Following CPT testing the subjects were asked “Did you feel a sensation other than cold and if yes, how would you describe it?” These responses were divided into ‘cold’ or non-noxious (pressure, nice, cold, tingling, pleasant and numb) and ‘non-cold’ or noxious (burning, ice, sharp, sting, gnawing and freezing) descriptors for further statistical analysis. Previous studies have reported the reliability of CPT measurement (Zwart and Trond, 2002; Wasner and Brock, 2008; Moloney et al., 2012). Testing was performed by one of two tes-ters (AS, BW). 2.8. Statistical analysis The average of 3 trials at each site was used for statistical analysis (Slater et al., 2005). CNSLBP subgroups were examined for differences in clinical profile using chi-squared tests, Fisher’s exact test, ManneWhitney U or KruskaleWallis tests as appropriate. The association between sensory threshold measures and variables considered as covariates (sex, age, waist/hip girth, DASS and PSQI) were examined using chi-squared tests, analysis of variance, ManneWhitney U or KruskaleWallis test as appropriate. Variables with evidence for imbalance among pain groups (p 0.200) were included in multivariable models. CPT values were suggestive of an underlying bimodal distribu-tion of this measure in the population (see Fig. 2), and all trans-formations including logarithmic failed to normalise the data. For further analysis we created a dichotomous variable based upon visual examination of the distribution of data for the CPT measure which supported a cut-off point of 15 C as clearly separating two groups in the data (15 C, 15 C, see Fig. 2). This dichotomisation was further supported by k-means cluster analysis, for which a two-cluster solution produced two clusters of individuals, with indi-vidual CPT measures below and above 15 C. Descriptive statistics and chi-squared tests were used to compare differences in pro-portions of participants with high CPT at each site between groups. Three binary logistic regressions with high/low CPT at each of the three sites as the outcome variable were used to assess pain group differences adjusting for covariates gender, DASS and PSQI. Differ-ences in frequency of use of non-cold descriptors of sensation experienced during testing between groups were tested using a chi-squared test. PPT measures were log transformed to correct for positive skew. General linear regression models with log transformed PPT mea-sures as the outcome variable were used to assess group differences unadjusted and adjusted for covariates gender, DASS and PSQI (three models for three sites). 95% Confidence intervals with associated p-values are presented for all regression coefficients. All data were analysed using the Statistical Package for Social Sciences (SPSS) student version 18.0 Table 1 Clinical profile of CNSLBP participants. Instrument (max score) (SPSS Inc., Chicago, IL, USA). Data were inputted by one researcher (CP) and cross-checked by a second researcher (AS). 3. Results Nineteen of the CNSLBP participants displayed NMP character-istics (4 males and 15 females with a mean age 42.6 (SD 14.8)) and 17 displayed MP characteristics (9 male and 8 females with a mean age of 39.4 (SD 14.2)). All subjects were screened for health complaints and none reported other co-existing pain conditions, diabetes, endocrine disorders, nervous system disorders or psy-chiatric disorders. Clinical characteristics of the pain groups are reported in Table 1. The NMP group was characterised by higher pain levels, more pain areas, a larger proportion of neuropathic pain as classified by PainDETECT scores, greater disability, higher risk rating on the SBST and greater frequency of medication use. Fig. 2 presents the untransformed individual values for CPT. Initial univariable analyses provided evidence of group differences in CPT at wrist, lumbar spine and heel sites, and PPT at the lumbar spine site (Table 2). The proportions of subjects with elevated CPTs (15 C) at the wrist were; control group 26%, MP group 24% and NMP group 84%. There was evidence of some imbalance between groups in DASS total, PSQI and gender, but not age orwaist-hip ratio (Table 3), and of various associations between sex, DASS total and Fig. 2. Untransformed individual values for CPT. Mechanical CNSLBP Non-mechanical CNSLBP p-Value Median (inter-quartile range), minemax VAS (10) 4 (4), 8e17 6 (3), 10e19 0.018a Widespread Pain Index (19) 2 (2), 1e7 3 (3), 1e9 0.014a RMDQ (24) 3 (6), 1e15 11 (11), 2e20 0.004a PainDETECT (39) Number (percentage of pain group) Nociceptive 14 of 17 (82%) 8 of 19 (42%) Unclear 3 of 17 (18%) 6 of 19 (32%) Neuropathic 0 5 of 19 (26%) 0.010b StarT Back score (9) Risk category Number (percentage of pain group) Low 11 of 17 (65%) 2 of 19 (11%) Medium 6 of 17 (35%) 9 of 19 (47%) High 0 of 17 (0%) 8 of 19 (42%) 0.001b Medication use Number (percentage of pain group) Non-opioid 1 of 17 (6%) 6 of 19 (32%) 0.052b NSAID 3 of 17 (18%) 8 of 19 (42%) 0.112b Opioid 0 of 17 (0%) 5 of 19 (26%) 0.023b Centrally acting 2 of 17 (12%) 6 of 19 (32%) 0.153b For each questionnaire, the maximum score is given in brackets. RMDQ, the Roland Morris Disability Questionnaire; VAS, a Visual Analogue Scale for pain on the day of testing; CNSLBP ¼chronic non-specific low back pain. a Statistical test for group differences is ManneWhitney U test. b Statistical test for group differences is Fisher’s exact test.
- 5. P. O’Sullivan et al. / Manual Therapy 19 (2014) 311e318 315 Table 2 Cold pain threshold (CPT) and pressure pain threshold (PPT) measures by participant group. Subgroup Control (n ¼ 19) Mechanical (n ¼ 17) Non-mechanical (n ¼ 19) p-Value CPT (n (%)15 C) Wrist 5 (26.3) 4 (23.5) 16 (84.2) 0.001b Lumbar spine 9 (47.4) 8 (47.1) 16 (84.2) 0.029b Heel 6 (31.6) 9 (52.9) 14 (73.7) 0.034b PPT (median (IQR), mm(Hg)) and Ln(PPT)a (mean (SD)) Wrist (untransformed) 301.3 (141.7) 302.0 (177.3) 239.7 (167.7) Ln(PPT) 5.73 (0.27) 5.66 (0.40) 5.59 (0.31) 0.416c Lumbar spine (untransformed) 352.7 (222.3) 288.7 (289.0) 183.0 (115.3) Ln(PPT) 5.84 (0.40) 5.72 (0.60) 5.14 (0.71) 0.001c Heel (untransformed) 309.3 (151.0) 315.0 (159.0) 270.3 (109.3) Ln(PPT) 5.76 (0.36) 5.78 (0.40) 5.58 (0.34) 0.055c Bold represent significant findings based on alpha of 0.05. PSQI and CPT measures, and between waist:hip ratio and PPT measures (Table 4). Therefore, DASS total, PSQI and sex were included in multivariable models as potential confounders. The results of the multivariable logistic regression model adjusting for sex, DASS total and PSQI for CPT at the wrist showed statistical evidence for group differences (Table 5). It was estimated that those patients in the NMP group had 18.4 (95% CI: 2.5e133.1, p¼0.004) times the odds of having an elevated (15 C) CPT to those in the MP group. This estimate was similar to the unadjusted odds ratio (OR) of 17.3 (p ¼ 0.001), meaning that sex, DASS total and PSQI were not important confounders of the association between group and CPT. CPT at the lumbar spine and heel sites was not statistically significantly different between NMP and MP groups after adjust-ment for covariates. At the lumbar spine, patients in the NMP group were estimated to have 5.9 (95% CI: 0.9e38.4, p ¼ 0.064) times the odds of having an elevated (15 C) CPT to those in the MP group after adjustment for sex, DASS total and PSQI, with the adjusted OR was similar in magnitude to the unadjusted estimate (6.0). At the heel, patients in the NMP had 6.3 (95% CI: 0.9e41.5, p¼ 0.058) times the odds of having an elevated (15 C) CPTcompared to those in the MP group adjusting for sex, DASS total and PSQI. At this site the adjusted OR (6.3) was larger than the unadjusted OR (2.5) which indicates the likely presence of negative confounding by covariates. At all sites there was no evidence that the MP group had greater or lesser odds than the control group for elevated CPT thresholds. The results of the linear regression models for PPT provided no evidence for group differences at any site (Table 5). Although there was some evidence that the NMP group had lower PPT than the MP group at the lumbar spine for the univariable model (difference: 0.58, 95% CI: 0.97 to 0.19, p ¼ 0.004), the model adjusted for sex, DASS total and PSQI did not confirm a difference existed independently of these covariates (difference: 0.37, 95% CI: 0.83 to 0.09, p ¼ 0.117). There were significant differences in the frequency of reporting of non-cold descriptors (at CPT) between groups at all three sites. Table 6 shows that the NMP group had the highest frequency of non-cold descriptors and controls the lowest. For the wrist and back sites the NMP group had a higher frequency than the MP group. 4. Discussion This study lends support to the presence of differences in PS profile between clinically determined subgroups of CNSLBP participants based on their pain characteristics, whilst adjusting for potential confounding factors known to influence sensory thresh-olds. The NMP group was estimated to have at least 2.5 times the odds of having cold hypersensitivity, as defined by a CPT greater than 15 C at the wrist, when compared to the MP CNSLBP group and the pain-free control group (95% CI for OR: 2.5e133.1, p ¼ 0.004), although the sample size was small and consequently confidence intervals for group differences were wide. Estimates of elevated CPT at the lumbar spine and heel were not statistically significant meaning that the null hypothesis of no difference be-tween groups cannot be rejected, however the pattern of larger odds of having cold hypersensitivity in the NMP group is consistent across all three sites, and it is possible that the lack of statistical significance is due to the low power of the study to detect possibly smaller effects at the lumbar spine and heel. Whilst a lower PPT in the NMP group at the lumbar spine was also detected, interestingly there was no statistical evidence for an independent group difference between the MP and control group after controlling for sex, sleep and psychological factors. These findings suggest that the changes in PPT observed in the NMP group may be mediated via gender differences, sleep deficits and/or psychological distress highlighting the multidimensional nature of PS. They also suggest that changes in PPT were limited to the lumbar test site. These findings however are at odds with previous reports where PPT was shown to be the best PS measure to distinguish a group of 40 patients with CNSLBP from pain-free controls after adjusting for age, gender, body compositions and psychological factors (Neziri et al., 2012). The differences in the findings may again reflect different patient profiles and methodo-logical differences. The findings of our study may explain some of the conflicting and variable findings in the previous PS research into CNSLBP dis-orders (Lewis et al., 2010; Attal et al., 2011; Blumenstiel et al., 2011; O’Neill et al., 2011; Hubsher et al., 2013; Neziri et al., 2012; Roussel et al., 2013), suggesting that NSCLNP is not a homogeneous group and that patient classification is one means by which to deal with this problem. Other authors have also proposed the need to classify NSCLBP patients based on neurophysiological mechanisms (Nijs et al., 2010; Smart et al., 2010; Woolf, 2011). Smart et al. (2010) also described a group of CNSLBP patients with ‘central sensitisa-tion’, defined by pain that is diffuse, lacks clear proportionate mechanical characteristics and present with associated psycho-logical factors. They defined a ‘nociceptive’ CNSLBP group by pain that is more intermittent, localised and responds to clear a Natural log transformation. b Statistical test for group differences is chi-squared test. c Statistical test for group differences is analysis of variance test.
- 6. P. O’Sullivan 316 et al. / Manual Therapy 19 (2014) 311e318 Table 3 Association between participant group membership and sex, age, waist:hip ratio, DASS and PSQI scores. Subgroup Control (n ¼ 19) Mechanical (n ¼ 17) Non-mechanical (n ¼ 19) p-Value Female sex (n (%)) 11 (57.9) 8 (47.1) 15 (79.0) 0.132b Age (mean (SD)) 42.6 (14.9) 39.4 (14.2) 41.9 (13.9) 0.788c Waist:hip ratio (mean (SD)) 0.83 (0.11) 0.85 (0.09) 0.85 (0.10) 0.696c DASS total (0e126a) (median (IQR)) 10 (14) 20 (18) 30 (34) 0.001d PSQI (0e21a) (mean (SD)) 4.3 (2.8) 7.7 (3.5) 11.0 (3.4) 0.001c Bold represent significant findings based on alpha of 0.05. aggravating and easing factors (Smart et al., 2010). Although not previously investigated against PS measures, these profiles are similar to the NMP and MP CNSLBP groups described. 4.1. Possible pain mechanisms It is proposed that central amplification of pain may be associ-ated with a number of changes within the central nervous system (CNS). These include neuronal hyperexcitability (Scott et al., 2005), enlarged receptor fields (Kasch et al., 2005), lowered thresholds of second order neurons (Kasch et al., 2005), reduced recruitment of pain modulating control systems (Campbell and Edwards, 2009), temporal summation (wind up) (Meeus and Nijs, 2007) and neuronal reorganisation (Woolf and Mannion,1999). These changes may be associated with a combination of factors including: sleep dysfunction, psychosocial factors and environmental/genetic in-teractions, influencing the immune-endocrine system and the neuromatrix, highlighting the complex multidimensional nature of persistent pain (O’Sullivan, 2012a). While peripheral sensitisation and some degree of segmental activity dependent central sensiti-sation might be anticipated for all patients with CNSLBP the development of widespread extra-segmental pressure hyperalgesia or the development of multi-modality sensitisation with either cold or heat hyperalgesia implies much more extensive changes in pain processing within the CNS. These changes are likely to involve many of the processes outlined above. These central amplification processes may also be linked to the presence of more constant and persistent pain. Interestingly therewas also a bimodal distribution for CPT in the pain-free control group demonstrating that a number of control subjects (26%) had elevated CPT, although their descriptors were different to the centrally amplified group. Whether this finding represents vulnerability in these subjects to future pain is not known but has been hypothesised previously (Woolf, 2011). The absence of PS differences between the MP and control group may reflect that MP participants’ spinal structures are sensitised to movement and/or load, but not local pressure (O’Sullivan, 2005; Dankaerts et al., 2009), or that the site where the PPT testing was applied was not specific to their pain location. Participants in the MP CNSLBP group also displayed lower levels of psychosocial fac-tors and sleep disturbance (Meeus and Nijs, 2007). Further research is required to determine the relationship between pain character-istics and PS to determine the role that central amplification has on patient clinical profiles. 4.2. Clinical relevance The classification of CNSLBP based on an underlying mechanism has been proposed to enhance targeted management (Deyo et al., 2009; O’Sullivan, 2012a; Woolf, 2011). While formal reliability testing of clinicians ability to discriminate these groups was not carried out, the results suggest that experienced physiotherapists were able to identify patients with different PS profiles, based on routine clinical examination (O’Sullivan, 2005; 2012b). Evaluation of cold hyperalgesia at the wrist may be combined with clinical assessment of patients to provide quantitative confirmation for patients who exhibit some degree of central amplification of their pain. Recent research in neck pain subjects indicates a pain response 5/10 with the application of ice indicated a 90% likeli-hood of laboratory measured CPT being 13 C (Maxwell and Sterling, 2013). These findings may have clinical application to the CNSLBP population described in this study, although further research is required to confirm this. Although speculative it would be interesting to investigate whether patients with MP respond better to locally targeted treatments, whereas patients with NMP require management ap-proaches that more specifically address central pain mechanisms. Clearly further research is required in larger populations of patients with CNSLBP to determine the validity of the clinical profiles and determine their predictive validity in relation to different targeted interventions as well as the ability of less experienced clinicians to reliably identify these patients. 4.3. Methodological considerations/limitations This study was only powered to detect large effect sizes, and consequently may have failed to detect smaller but still clinically meaningful differences between groups. As a consequence of the small sample size, the confidence intervals for the elevated odds of cold hypersensitivity in the NMP group were very wide, limiting a Minimum to maximum score possible. b Statistical test for group differences is chi-squared. c Statistical test for group differences is analysis of variance. d Statistical test for group differences is KruskaleWallis test. Table 4 Associations between cold (15 C, 15 C) and pressure pain (ln(PPT)) threshold measures and sex, age, waist:hip ratio, DASS and PSQI scores. CPT PPT Wrist Lx Heel Wrist Lx Heel Sex 0.116d 0.122d 0.080d 0.166c 0.236c 0.094c Age 0.006c 0.133c L0.365c** 0.240b 0.254b 0.278b* Waist:hip ratio 0.001c 0.071c 0.040c 0.285a* 0.069a 0.273a* DASS total 0.312c* 0.177c 0.038c 0.042b L0.394b** 0.110b PSQI 0.336c* 0.290c* 0.141c 0.031a L0.400a** 0.550a Bold represent significant findings based on alpha of 0.05. Lx ¼ lumbar spine. *p 0.05; **p 0.01. a Measure of association is Pearson correlation coefficient. b Measure of association is Spearman correlation coefficient. c Measure of association is Point-biserial correlation coefficient. d Measure of association is Phi correlation coefficient.
- 7. P. O’Sullivan et al. / Manual Therapy 19 (2014) 311e318 317 Table 5 Adjusted and unadjusted parameter estimates for group membership from univariable and multivariable binary logistic regression (CPT: 15 C, 15 C) and general linear (ln(PPT)) models (multivariable models adjusted for gender, DASS total and PSQI). Cold pain threshold Unadjusted Adjusted precise estimation of this association in the population under study. Furthermore, for PPT, testing at a generic site at the lumbar spine may not detect local hyperalgesia. Previous authors have successfully tested PPT in patients with CNSLBP at the site of most severe pain and found it to be predictivewith pain, independent of potential confounders (Neziri et al., 2012). Pain medication use was only reported in CNSLBP participants, which precluded use of this variable in the multivariable models presented. However, group differences in medication use were not large (Table 6) and current pain medication use was not associated with CPT or PPT. Other variables only assessed in CNSLBP participants and associ-ated with pain group membership, such as pain intensity, number of pain areas, RMDQ and SBST, were not considered as con-founders of the group membership/pain threshold association in this study as they represented part of the common clinical profile of these groups and thus consequences of differential sensory processing. The inter-therapist reliability of the ability of Physio-therapists to differentiate NP from NMP requires further investi-gation and larger studies are required to verify these results. 5. Conclusion This study provides preliminary evidence that two patient groups with CNSLBP identified clinically, can be distinguished based on their PS profile. 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