This is the first study to illustrate and show the remarkably detailed expressions of knee pain patterns, as drawn on high-resolution 3D digital body-schema of the knees, from adolescents and young adults with long-standing PFP. Moreover, exploration and quantification of the knee pain area, location and distribution revealed PFP complaints were common in the lower peripatellar region and a somewhat specific expansion of pain spread tended towards the upper peripatellar region for those with an extended (greater than 5 years) duration of PFP symptoms. Only one individual with PFP presented with pain restricted to the retropatellar area while the majority presented with a pain pattern restricted to the peripatellar region. Furthermore, a high number of individuals with bilateral PFP presenting with a symmetrical pain pattern demonstrated a mirrored expression of pain in the left and right knee in terms of location, shape and size. Classification of symmetry in PFP was explored using subjective and objective mathematical approaches, which resulted in the finding that PFP experts may be stricter when visually classifying the degree of symmetry in PFP pain patterns.
Pain localization
The pain localization found in the current study resembles previous work on adolescents with PFP and further highlights that the majority of individuals have peripatellar or peripatellar mixed with retropatellar pain [
6]. In accordance to a separate study with young adults (mean age 21) the most common pain localization (83%) was in the peripatellar region [
23]. Brushøj et al. and colleagues (2008) suggest that the report of pain within the peri-patellar region supports the notion that synovium is involved in the genesis of PFP. For this study, there is also clear spatial overlap for the majority, regardless of symptom duration, around the lower part of the patella which is consistent with proposed involvement of Hoffas fat pad in PFP [
23].
The spatial overlap of the pain patterns is higher in the PFP group with extended pain duration and the pattern itself appears to progress from a “U” to an “O” shape around the peripaterllar region. The progression may reflect a generally less uniform or more variable pain pattern to a more uniform or less variable presentation of pain in a duration-dependent manner. If this is the case, the results give rise to the notion that there is a convergence towards a specific pattern, which is an “O” shape, as symptom duration progresses.
Signature and symmetrical knee pain patterns
Sixty years ago, Palmer stated that symmetry “is almost diagnostic of a functional nervous disorder, or the functional superstructure which the patient may have built up around [an] organic lesion'' [
24]. In this investigation, approximately three out of every four patients presented with bilateral PFP and the majority of those individuals expressed their on-going pain with a remarkable degree of similarity between the left and right knee. Of particular interest for this present study was the extraction of the common locations of pain, such that information about pain location with respect to retropatellar or peripatellar regions could be contrasted with known and underlying structures and pathophysiology of long-standing PFP. In consideration of earlier queries [
25,
26] and pivotal investigations [
27] on the topic of mirror-image pain and neurogenic inflammation, the emergence of symmetrical mirror-image bilateral ‘knee-pain’ patterns was difficult to interpret. To our knowledge, detailed reports of on-going symmetrical pain expressions within a complex structure, such as the knees in humans, have yet to be elaborated upon, or at best qualitatively reported. Indeed, the concept of symmetry in pain as a symptom, with regards to spatially-specific areas of symptom location and/or the degree of symptom progression as expressed on the left and right side of the body has been reported [
28‐
30]. The symmetrical presentation of symptoms occurring in spatially specific areas is known to be a cardinal feature in diseases such as rheumatoid arthritis and psoriasis [
26]; where symmetry is the norm rather than the exception. However, it has been proposed that patients presenting with asymmetrical pain may advance towards symmetry (symmetrization) as a disease (e.g. rheumatoid arthritis) progresses and therefore may be of importance for the clinical management of the disease [
30]. To date, PFP is often described as diffuse anterior knee pain during activities that load the patellofemoral joint such as stair walking, walking or running and some may communicate their pain by ‘placing both hands over their knees to indicate the area of pain’ or ‘point to the area around the knee such that pain is described as taking a classic or signature
C-sign’ [
14]. Clearly, clinical recordings of referred pain area, location, and descriptions of the pain expression reported in association with PFP have received less attention in this respect. In related fields of knee pain, these features are however, within the top seven of the most important outcome variables for post-surgical knee pain success [
31].
Mirror-image pain is traditionally known as pain experienced on both sides of the body, as a result of trauma or inflammation in one limb. The recognition that symptoms occur in symmetrical locations, such as within the left and right hand and ankle joints in rheumatoid arthritis, encouraged seminal and pioneering investigations on the contralateral effects of pro-inflammatory mediators induced by unilateral nerve injury [
27,
32]. By the late 1990s the notion that unilateral peripheral nerve lesions affect spatially-specific contralateral (undamaged) structures gained momentum and it became clear that the contralateral effects of a peripheral nerve lesion were not limited to the up-regulation of pro-inflammatory mediators but that gene expression, physiologic and anatomical remodeling could also occur [
25]. Even models of unilateral muscle overuse injuries have been shown to up-regulate the tachykinin system bilaterally [
33]. Tendency towards symmetry as a disease progresses has been reported for patients with rheumatoid arthritis, such that the grade of damage becomes symmetrical between paired joints, as assessed by radiography [
30]. Particularly relevant for this present study, is that unilateral joint inflammation of the cartilage can lead to bilateral degeneration of knee cartilage in rats [
34] which supports the possibility that symmetrical mirror-image pain in long-standing PFP may be indicative of both mechanism and progression of PFP. A possibility for the emergence of symmetrical mirror-image knee pain in adolescents and young adults with PFP may simply be abnormal knee or joint biomechanics. Given that PFP is usually provoked by bilateral weight-bearing activities, such as stair climbing, walking or running, then abnormal knee or joint biomechanics may exacerbate or lead to the development of premature ‘overuse’ injuries in both knees. Thus, symmetrical pain or mirror-image PFP may simply reflect a bilateral exposure to ‘overuse’ of associated muscle and tissue knee structures. Nonetheless, it may be highly relevant to track the progression of PFP patterns and associated degree of symmetry as the disease or duration of symptoms progresses until a better understanding of the pathophysiology and driving mechanisms are clear.
In this study, we have explored and contrasted subjective and objective means of classifying bilateral PFP patterns as symmetric or non-symmetric. Further, we assessed the level of symmetry between two drawings that were intended to be symmetrical in order to threshold for natural pain drawing variation. Classical mathematical approaches for assessing symmetry could be ascertained with a 100% TPR and 20% FPR. Altogether the results showed that the PFP expert in this study was stricter when assigning symmetry classification as compared to the mathematical approaches. The FPR found in this study is attributed to the location differences in pain drawn on the left and right knee, with the PFP expert applying knowledge and weighting significance onto the underlying anatomical structures to guide symmetry classification. Nonetheless, the degree of symmetry in the PFP patterns are evident, quantifiable, and thought provoking.
It remains to be determined the time course of pain area expansion or spread in PFP symptoms as the condition progresses and whether (1) the pain area expansion is a key metric for symptom progression and (2) if symptoms progress towards symmetry with symptom duration and (3) if simple fuzzy rules and classification approaches then become more robust with symptom duration. Such data would be useful in determining if there is a systematic expansion in pain area as implicated by studies of knee pain drawings in knee osteoarthritis arthritis (OA) showing that global, rather than localized pain, is associated with worse self-reported pain and function [
35].
A limitation of this study is the low number of subjects and the median split used to sub-divide the PFP symptom duration, and thus these results need to be replicated in a large external cohort of patients with PFP in order to get a better indication of the role. Recently it has been shown that the size of the pain drawing areas in knee OA patients was not specifically correlated to preoccupation, attention, catastrophizing, or fear of pain but rather indirect assessments of central sensitization [
36]. Therefore, the presence and significance of the degree of symmetry, as revealed by pain drawings, should further explored as an objective measure of symptom progression.
‘Extended’ long-standing knee pain
In this study, a majority of those with long-standing PFP showed bilateral symmetrical mirror-image pain so subgrouping based on the presence or absence of this condition was not feasible (i.e. symmetrical vs. asymmetrical knee pain), and therefore currently limits further query in this regard. However, those with extended long-standing PFP indicated that the area of pain was greater than those presenting with PFP symptoms for less than 5 years. Moreover, those with PFP symptoms for 5 years or more showed a strong positive correlation between current pain intensity and area which supports theoretical models for development of chronic widespread pain [
37]. Recent evidence suggest that adolescents with PFP demonstrate reduced pressure pain thresholds remote from the site of self-reported pain, which implicates altered central processing of sensory input [
6]. Collectively, these findings challenge the current understanding and awareness of PFP in adolescents and young adults and supports that PFP should be regarded as “a knee condition with high rate of persistence and features of central involvement” [
6,
9,
37].