Pressure pain thresholds in adults with patellofemoral pain and patellofemoral joint osteoarthritis: a case-control study

2.1 Participant recruitment

Patients diagnosed with PFP or PFJOA were included after consultation and examination by a member of their usual care team at Pure Sports Medicine (PSM), sports medicine clinic. Patients diagnosed with PFP or PFJOA were required to meet the inclusion and exclusion criteria outlined in Table 1 which mirror previous studies [16], [17], [20], [21], a PFP Diagnostic Checklist [32], diagnostic criteria from the 2016 PFP Consensus [10] and the EULAR recommendations for the clinical diagnosis of knee osteoarthritis [33]. More specific PFJOA tests, such as crepitus and pain on patellofemoral compression, lack sensitivity and specificity so were not used [34], [35]. Individuals who met the inclusion criteria were dichotomised into PFP and PFJOA groups based on age, with the PFP group aged 18–40 years and the PFJOA group aged above 40 years [33], [36]. Patient recruitment and data collection occurred at PSM between April 2017 and May 2018.

Age, sex and activity level matched controls were recruited from Queen Mary University of London (QMUL) through email advertisements, verbal information to lecture attendees and word of mouth. Controls were required to have no knee pathologies or history of PFP or PFJOA, no previous knee surgery, no known neurological disease, aged above 18 years and able to understand English. Control recruitment and data collection occurred at QMUL between January 2018 and May 2018.

2.2 Sample size

Sample size was calculated using the G*Power Programme [37] based on a previous study by Rathleff et al. investigating PPTs in PFP patients compared to controls [26]. Using reported PPT means (306.2, 484.2) and standard deviations (±122.9, ±134.7), a power of 80% and an alpha level of 0.05, a sample of 15 PFP patients and 15 matched controls were indicated. Although this study is specific to PFP, the sample size was also applied to the PFJOA group owing to the absence of published studies exploring PPTs in PFJOA and the accepted consensus that PFP and PFJOA lie on a continuum [5], [6], [7], [8], [9]. Hence, a further 15 PFJOA patients and 15 matched controls required recruitment.

2.3 Measurements

Participants completed a questionnaire to record demographics (age, sex, height, weight), painful side (patients) or dominant leg (controls) and Tegner score [38]. Additionally, patients recorded symptom duration in months and Kujala score (PFP patients) or KOOS-PF score (PFJOA patients) [39], [40]. Tegner score is a self-reported measure of activity with scores ranging from Level 0 (sick leave or disability pension) to Level 10 (national elite competitive sports player). Kujala score and KOOS-PF score are condition specific questionnaires assessing PFP and PFJOA severity respectively through a series of questions covering subjective symptoms and functional limitations giving a score out of 100.

2.3.1 Single leg squat

Participants performed five single leg squats (SLS) either on the painful side in patients or dominant leg in controls. The assessor demonstrated a SLS before sitting 2 m away and video recording the participant (Fig. 1). The camera was angled to capture the participant from shoulder to floor excluding the face for confidentiality (Fig. 2). SLS were completed prior to PPT testing, since tend to exacerbate symptoms, making the PPTs more representative of knee sensitivity during ADL [20].

Fig. 1:

Method for SLS video recording (examiner seated 2 m away with the participant in front of a blank background).

Fig. 2:

SLS camera angle (capturing participant from shoulder to floor taking care to exclude face) and normal SLS progression.

SLS videos were visually rated by two assessors (CB, LE) using a modified version of the Whatman Score. The Whatman score is a seven-item checklist to rank lower extremity functional tests based on lower limb positioning and balance, with higher scores indicating poorer functional ability [41]. Since it is not specific to SLSs, it was identified that the depth of squats achieved by participants may confound results, with those performing only a shallow SLS, due to poor knee function, achieving low overall scores. Thus, an additional criterion was added to reflect SLS depth, with assessors rating SLSs either deep, medium, or shallow with the total score then multiplied by 1, 2 or 3, respectively.

2.3.2 Pressure pain thresholds

PPTs were recorded using a handheld pressure algometer with a 1 cm² rubber tip (Wagner FDX25™, Wagner Instruments, Greenwich, CT, USA). Units were measured in newtons (N) with a 0.01 N graduation. In common with Pazzinatto et al. participants were positioned in a standardised position, lying supine on an examination table with knees fully extended [20], [21]. Six sites were tested either on the painful side (patients) or dominant leg (controls) (Fig. 3). Five sites were local to the knee to assess for local hyperalgesia (medial, superior, lateral, central, ipsilateral tibialis anterior), as previously defined by Rathleff et al. [27] one site was remote to assess for distal hyperalgesia (contralateral tibialis anterior) (Table 2).

Fig. 3:

PPT test sites (numbers correspond to Table 2).

Table 2:

Detailed descriptions of PPT sites.

Site number	Site name	Location
1	Medial	3 cm medial to the midpoint of the medial edge of the patella
2	Superior	2 cm proximal to the superior edge of the patella
3	Lateral	3 cm lateral to the midpoint on the lateral edge of the patella
4	Central	Centre of patella
5	Ipsilateral tibialis anterior	Ipsilateral muscle belly of tibialis anterior, 5 cm distal to the tibial tuberosity
6	Contralateral tibialis anterior	Contralateral muscle belly of tibialis anterior, 5 cm distal to the tibial tuberosity

1. cm=centimeters.

One of three assessors (CB, LE, SL) recorded the PPT at each of the six sites. The same technique was followed, as previously outlined by van der Heijden et al. [29] placing the tip perpendicular to the skin and applying slow and steady pressure, taking care to stabilise any nodular muscular regions particularly when over the patella (Fig. 4). Participants indicated when the sensation changed from a comfortable to uncomfortable pressure, at which point the assessor removed the algometer and recorded the maximum applied force.

Fig. 4:

Example of PPT testing (at superior site).

2.4 Reliability

Interclass correlation coefficients (ICC) and 95% confidence intervals (CI) were calculated based on an absolute agreement, two-way random-effects model. The guidelines for interpreting ICC are: <0.50 poor, 0.50–0.75 moderate, 0.75–0.90 good, ≥0.90 excellent [42].

2.5 Statistical analysis

All analyses were performed using the Statistical Package for the Social Sciences software programme (SPSS 25.0, IBM, Chicago, IL, USA) with an a priori level of 0.05. Normality and variance homogeneity were tested using the Shapiro-Wilk and Levene’s test respectively. Normally distributed data was presented as mean and standard deviation (SD) and non-normally distributed data was presented as median and interquartile range (IQR).

Group differences were compared using Independent-Samples t-test for numeric variables with normal distribution, Mann-Whitney U-test for numeric variables with non-normal distribution and the chi-square (χ²) Test for nominal variables. A two-way mixed model analysis of variance (ANOVA) with repeated measures was performed to test between group differences in PPTs. Outliers due to genuinely unusual values were not excluded if determined not to significantly influence results. There was homogeneity of variances and covariances, as assessed by Levene’s Test and Box’s Test respectively. Mauchly’s Test indicated that the assumption of sphericity was violated for the two-way interaction [χ²(14)=30.152, p=0.007], hence, a Greenhouse-Geisser correction was applied to all tests. In cases of significant interactions, Tuckey’s post hoc test was performed, allowing multiple pairwise comparisons. The data reported was the F values, p-values and partial eta squared. The guidelines for interpreting eta squared are: 0.01=small effect, 0.06=moderate effect, 0.14=large effect [43]. Spearman rank-order correlation was used to test the association between the five local sites mean and Kujala or KOOS-PF score and Modified Whatman score.

3.1 Participant characteristics

No differences between PFP patients (n=13) and controls (n=20) were detected for height, weight, BMI or Tegner score (p>0.05). Age was higher in the PFP compared to control group (PFP median 30.0, IQR 6.50; control median 23.0, IQR 7.00; p=0.002). Between-group sex differences were noted with 85% females in the PFP group compared to 50% females in the control group (χ²=4.08, p=0.043) (Table 3).

No differences between PFJOA patients (n=15) and controls (n=34) were detected for sex, height, weight or BMI (p>0.05). Age was lower in the PFJOA compared to control group (PFJOA mean 49.4, SD±8.51; control mean 58.3, SD±9.83; p=0.004). Activity level, measured by Tegner score, was lower in the PFJOA compared to control group (PFJOA median 4.00, IQR 2.00; control median 5.00, IQR 2.00; p=0.039) (Table 4).

3.2 Symptomatic versus control

No interaction was observed between the symptomatic PFP and PFJOA group (n=28) and the asymptomatic control group (n=54) across all six PPT sites [F(5,400)=1.537, p=0.190, partial η²=0.019, ε=0.816].

For PFP versus controls, no interaction between group and PPT sites were observed [F(5,155)=1.612, p=0.183, partial η²=0.049, ε=0.705] (Fig. 5). The main effect of group showed no difference between PPTs [F(1,31)=0.687, p=0.413, partial η²=0.022]. The main effect of site showed a difference between PPT sites [F(5,155)=2.834, p=0.034, partial η²=0.084, ε=0.705]. Post-hoc analysis revealed the medial site to be lower than the other five sites (p<0.05).

Fig. 5:

PPTs at the six test sites in PFP patients versus matched controls (individual patient data with group median and IQR bars).

For PFJOA versus controls, no interaction between group and PPT sites were observed [F(5,235)=0.764, p=0.550, partial η²=0.016, ε=0.803] (Fig. 6). The main effect of group showed no difference between PPTs [F(1,47)=0.237, p=0.629, partial η²=0.005]. The main effect of site showed a difference between PPT sites [F(5,235)=4.506, p=0.002, partial η²=0.087, ε=0.803]. Post-hoc analysis revealed the superior site to be higher than the other five sites (p<0.05).

Fig. 6:

PPTs at the six test sites in PFJOA patients versus matched controls (individual patient data with group median and IQR bars).

3.3 Condition severity and knee function

No correlation was found between Kujala score and local site mean (r_s=0.372, p=0.211) or KOOS-PF score and local site mean (r_s=−0.235, p=0.400). Modified Whatman score was found to be higher in PFP patients compared to controls (PFP median 14.0, IQR 6.00; control median 9.00, IQR 11.8; p=0.037), however, no difference was detected in PFJOA patients compared to controls (PFJOA mean 20.5, SD±6.44; control mean 16.1, SD±7.64; p=0.089). No correlation was found between Modified Whatman score and local site mean in the PFP group (r_s=−0.137, p=0.446) or the PFJOA group (r_s=−0.247, p=0.107).

4.1 Symptomatic versus control

Previous studies investigating PPTs in PFP have recruited a predominately adolescent population, which differed significantly from the middle-aged population recruited within this study [20], [21], [25], [26], [27], [28]. Emerging evidence suggest childhood and adolescence are critical periods where pain experience can prime nociceptors inducing long-lasting effects not seen amongst adults [45]. Consequently, pain sensitisation may be age dependent and amplified in patients under 18 years, offering a plausible explanation for the difference observed [26], [27]. Two recent studies have found conflicting results of PPT scores in mixed-sex adult PFP populations, with van der Heijden et al. reporting reduced PPTs and Rathleff et al. reporting no between-group difference [22], [29]. In knee osteoarthritis, research indicates early involvement of the patellofemoral joint [46]. PFP and PFJOA lie on a disease continuum, with radiographic and MRI features of PFJOA identified in 20–30% of PFP patients [5], [6], [7], [8], [9], [47]. Correspondingly, PFJOA patients in this study were notably younger with a mean age of 49.4 years compared to knee osteoarthritis studies recruiting patients with a mean age of 65 to 70 years [48], [49], [50], [51], [52], [53], [54]. Literature is divided in regard to age interactions on pain sensitisation in knee osteoarthritis with evidence for both reduced and increased PPTs with ageing [55], [56]. This inconsistency raises the possibility that sensitisation is a “trait” rather than a “state” with hypersensitivity relating to an individual’s predisposition to sensitisation opposed to being induced by peripheral pain processing changes [51].

Reports of pain sensitisation in PFP and PFJOA are dominated by female participants [20], [21], [25], [26], [27], [28], [48], [49], [57], [58]. Females with both PFP and PFJOA are well documented to experience greater pain sensitivity to experimental pain such as PPTs [56], [59], [60], with evidence suggesting less efficient endogenous pain inhibition systems in females [61]. It is possible that pain sensitisation is not such a dominant feature of males with PFP and PFJOA with the inclusion of males in this study contributing to the inconsistent findings. The sex of the population may act as a confounding factor in this study being a key determinant of PPTs and highlighting the importance of interpreting the findings within a specific population context. Certainly, further research exploring gender differences in pain sensitisation in PFP and PFJOA is required to provide a more robust evidence base.

The duration of patient’s symptoms was comparitvely short in our included study population (a median of 22 months in PFP and 18 months in PFJOA) when compared with previous studies, especially knee osteoarthritis which frequently recruit knee replacement candidates [19], [48], [49], [50], [52], [57], [62], [63], [64]. Symptom duration has been both positively and negatively associated with manifestations of hyperalgesia [19], [26]. It is clear that time required to develop hyperalgesia varies between conditions, for example 1 month in whiplash versus 5 years in rheumatoid arthritis, but this time remains unclear in PFP and PFJOA [65], [66]. A graduated involvement of the nervous system is thought to occur producing sensitisation in a time-dependent manner [19]. Since symptom durations were relatively short in this study it is possible not all patients had developed manifestations of pain sensitisation.

Tegner score was well matched in the PFP patients and controls, however, was reduced in the PFJOA patients compared to the control group. Whilst clinical measures indicated the absence of sensitisation or reduced functional capacity, the reduced Tegner score in the PFJOA patients may be indicative of a decreased want or willingness to be involved in physical activity. It is important for this population, in particular, to remain active and maintain a healthy BMI, cardiovascular fitness and muscle strength for overall health. Given the disparity observed in the results, further investigation and possible implementation of interventions to affect behavioural change may be required.

4.2 Condition severity and knee function

PFP patients had less severe knee pain, indicated by better Kujala scores than reported in previous studies [20], [21], [22], [25], [26], [27], 29]. Similarly, PFJOA patients had a mean KOOS-PF score of 55.2 reflecting a mid-range score suggesting moderate PFJOA. The reduced severity of both of these patient groups may reflect similar findings of no alteration in PPTs in patients with mild/moderate PFJOA but lower PPTs in those with severe PFJOA reported previously [19]. The inclusion of patients with less severe pain might have reduced the likelihood of detecting pain sensitivity. Ensuring a broader spread of symptom severity and duration within the included population of future studies could offer greater differentiation within patient groups and may better explore the correlation between PPTs and Kujala or KOOS-PF scores.

Modified Whatman score was found to be reduced in PFP patients compared to controls. Individuals with PFP have been shown to adopt compensatory movement strategies in response to pain to avoid excessive patellofemoral joint stress [67]. One such strategy is reduced knee flexion during stair negotiation [68], [69], [70], [71], associated with fear of movement, or kinesiophobia, driving altered kinematics [69], [72], [73]. Kinesiophobia, more than pain sensitivity, may have contributed to the impaired SLS quality observed in this study, representing a critical component in the disconnect between movement patterns and pain sensitivity scores. Since a reduction in kinesiophobia has been shown to improve pain and disability this may highlight a potential need to provide additional interventions to address non-physical impairments in order to better treat PFP [72], [74].

4.3 Strengths, limitations and future directions

To our knowledge, this is the first UK based case-control study exploring pain sensitisation in mixed sex adults with PFP and PFJOA. Furthermore, it is the first study to isolate PFJOA from knee osteoarthritis and test for pain sensitisation. The inclusion and exclusion criteria were well constructed following previous studies, a PFP Diagnostic Checklist, the 2016 PFP Consensus and the EULAR recommendations for the diagnosis of knee osteoarthritis.

However, this study is not without methodological limitations. Assessor binding to group was not feasible introducing the risk of detection bias. There is a possibility of population bias since the population was not recruited from a large, well defined cohort. External validity may have been reduced since patients were recruited only from a single private sports medicine clinic. Between-group age and sex differences were identified with better control matching being preferable. As such, results require cautious interpretation with further research required to confirm the lack of between-group difference.

PPTs reflect peripheral sensitisation, testing hyperalgesia of superficial structures only. Past literature has included measures of central sensitisation, such as conditioned pain modulation and temporal summation, but these were beyond the scope of this study [22], [27]. It has previously been proposed that measuring hyperalgesia of deep chondral bone may provide new insights into the manifestations of pain both peripherally and centrally [22]. Future studies will require the development of an appropriate tool before this can be explored since to date no such instrument exists.

4.4 Conclusion

No difference in PPTs between patients with PFP and PFJOA compared to age, sex and activity level matched controls were identified. Furthermore, PPTs were found to be independent of condition severity and knee function. Peripheral pain processing changes leading to pain sensitisation does not appear to be a dominant feature of PFP or PFJOA within a UK mixed-sex adult population. However, PFP and PFJOA remain persistent pain complaints which may not be well explained by objective measures of sensitivity such as PPTs. Findings suggest the pain pathway involved in these conditions for many people remains primary nociceptive possibly with a subgroup in whom pain sensitisation is a feature. In order to deliver a patient centred management approach assessment of a patient’s pain presentation may be required.