Aims. To identify the prevalence of neuropathic pain after lower limb fracture surgery, assess associations with pain severity, quality of life and disability, and determine baseline predictors of chronic neuropathic pain at three and at six months post-injury. Methods. Secondary analysis of a UK multicentre randomized controlled trial (Wound Healing in Surgery for Trauma; WHiST) dataset including adults aged 16 years or over following surgery for lower limb major trauma. The trial recruited 1,547 participants from 24 trauma centres. Neuropathic pain was measured at three and six months using the Doleur Neuropathique Questionnaire (DN4); 701 participants provided a DN4 score at three months and 781 at six months. Overall, 933 participants provided DN4 for at least one time point. Physical disability (Disability Rating Index (DRI) 0 to 100) and health-related quality-of-life (EuroQol five-dimension five-level; EQ-5D-5L) were measured. Candidate predictors of neuropathic pain included sex, age, BMI, injury mechanism, concurrent injury, diabetes, smoking, alcohol, analgaesia use pre-injury, index surgery location, fixation type, Injury Severity Score, open injury, and wound care. Results. The median age of the participants was 51 years (interquartile range 35 to 64). At three and six months post-injury respectively, 32% (222/702) and 30% (234/787) had neuropathic pain, 56% (396/702) and 53% (413/787) had chronic pain without neuropathic characteristics, and the remainder were pain-free. Pain severity was higher among those with neuropathic pain. Linear regression analyses found that those with neuropathic pain at six months post-injury had more physical disability (DRI adjusted mean difference 11.49 (95% confidence interval (CI) 7.84 to 15.14; p < 0.001) and poorer quality of life (EQ-5D utility -0.15 (95% CI -0.19 to -0.11); p < 0.001) compared to those without neuropathic characteristics. Logistic regression identified that prognostic factors of younger age, current smoker, below knee fracture, concurrent injuries, and regular analgaesia pre-injury were associated with higher odds of post-injury neuropathic pain. Conclusion. Pain with neuropathic characteristics is common after lower limb fracture surgery and persists to six months post-injury. Persistent neuropathic pain is associated with substantially poorer recovery. Further attention to identify neuropathic pain post-lower limb injury, predicting patients at risk, and targeting interventions, is indicated. Cite this article: Bone Joint J 2021;103-B(6):1047–1054

Aims. Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH. Methods. This cross-sectional study was carried out according to the “STrengthening the Reporting of OBservational studies in Epidemiology” statement. Data on 19 variables were collected at a single timepoint from 250 patients with ONFH who were treated at our medical centre between July and December 2023 using validated instruments or, in the case of hip pain, a numerical rating scale. Factors associated with pain severity were identified using hierarchical multifactor linear regression. Results. Regression identified the following characteristics as independently associated with higher pain score, after adjustment for potential confounders: Association Research Circulation Osseous classification stage IIIa or IIIb, bone marrow oedema, grade 3 joint effusion, as well as higher scores on pain catastrophizing, anxiety, and central sensitization. The final model explained 69.7% of observed variance in pain scores, of which clinical and radiological factors explained 37%, while psychological and neurophysiological factors explained 24% and demographic factors explained 8.7%. Conclusion. Multidimensional characteristics jointly contribute to the severity of pain associated with ONFH. These findings highlight the need to comprehensively identify potential contributors to pain, and to personalize management and treatment accordingly. Cite this article: Bone Joint Res 2024;13(11):673–681

We identified a group of patients from the Swedish Arthroplasty Register who reported no relief of pain or worse pain one year after a total knee replacement (TKR). A total of two different patient-reported pain scores were used during this process. We then evaluated how the instruments used to measure pain affected the number of patients who reported no relief of pain or worse pain, and the relative effect of potential risk factors. . Between 2008 and 2010, 2883 TKRs were performed for osteoarthritis in two Swedish arthroplasty units. After applying exclusion criteria, 2123 primary TKRs (2123 patients) were included in the study. The Knee injury and Osteoarthritis Outcome Score (KOOS) and a Visual Analogue Scale (VAS) for knee pain were used to assess patients pre-operatively and one year post-operatively. . Only 50 of the 220 patients (23%) who reported no pain relief on either the KOOS pain subscale or the VAS for knee pain did so with both of these instruments. Patients who reported no pain relief on either measure tended to have less pain pre-operatively but a higher degree of anxiety. Charnley category C was a predictor for not gaining pain relief as measured on a VAS for knee pain. . The number of patients who are not relieved of pain after a TKR differs considerably depending on the instrument used to measure pain. . Cite this article: Bone Joint J 2014;96-B:1222–6

Aims. The aim of the study was to determine if there was a direct correlation between the pain and disability experienced by patients and size of their disc prolapse, measured by the disc’s cross-sectional area on T2 axial MRI scans. Methods. Patients were asked to prospectively complete visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores on the day of their MRI scan. All patients with primary disc herniation were included. Exclusion criteria included recurrent disc herniation, cauda equina syndrome, or any other associated spinal pathology. T2 weighted MRI scans were reviewed on picture archiving and communications software. The T2 axial image showing the disc protrusion with the largest cross sectional area was used for measurements. The area of the disc and canal were measured at this level. The size of the disc was measured as a percentage of the cross-sectional area of the spinal canal on the chosen image. The VAS leg pain and ODI scores were each correlated with the size of the disc using the Pearson correlation coefficient (PCC). Intraobserver reliability for MRI measurement was assessed using the interclass correlation coefficient (ICC). We assessed if the position of the disc prolapse (central, lateral recess, or foraminal) altered the symptoms described by the patient. The VAS and ODI scores from central and lateral recess disc prolapses were compared. Results. A total of 56 patients (mean age 41.1 years (22.8 to 70.3)) were included. A high degree of intraobserver reliability was observed for MRI measurement: single measure ICC was 0.99 (95% confidence interval (CI) from 0.97 to 0.99 (p < 0.001)). The PCC comparing VAS leg scores with canal occupancy for herniated disc was 0.056. The PCC comparing ODI for herniated disc was 0.070. We found 13 disc prolapses centrally and 43 lateral recess prolapses. There were no foraminal prolapses in this group. The position of the prolapse was not found to be related to the mean VAS score or ODI experienced by the patients (VAS, p = 0.251; ODI, p = 0.093). Conclusion. The results of the statistical analysis show that there is no direct correlation between the size or position of the disc prolapse and a patient’s symptoms. The symptoms experienced by patients should be the primary concern in deciding to perform discectomy. Cite this article: Bone Joint J 2022;104-B(6):715–720

Aims. This study sought to estimate the clinical outcomes and describe the nationwide variation in practice, as part of the feasibility workup for a National Institute for Health and Care Excellence (NICE) recommended randomized clinical trial to determine the optimal treatment of torus fractures of the distal radius in children. Methods. Prospective data collection on torus fractures presenting to our emergency department. Patient consent and study information, including a copy of the Wong-Baker Faces pain score, was issued at the first patient contact. An automated text message service recorded pain scores at days 0, 3, 7, 21, and 42 postinjury. A cross-sectional survey of current accident and emergency practice in the UK was also undertaken to gauge current practice following the publication of NICE guidance. Results. In all, 30 patients with a mean age of 8.9 years were enrolled over a six-week period. Of the 150 potential data points, data was captured in 146, making the data 97.3% complete. Pain scores were recorded at day 0 (mean 6.5 (95% confidence interval (CI) 5.7 to 7.3)), day 3 (4.4 (95% CI 3.5 to 5.2)), day 7 (3.0 (95% CI 2.3 to 3.6)), day 21 (1.2 (95% CI 0.7 to 1.7)) and day 42 (0.4 (95% CI 0.1 to 0.7)). Of the 100 units who participated in the nationwide survey, 38% were unaware of any local or national protocols regarding torus fractures, 41% treated torus fractures with cast immobilization, and over 60% of patients had follow-up arranged, both contradictory to national guidelines. Conclusion. We have demonstrated the severity, recovery trajectory, and variation in pain scores among children with torus fractures. We demonstrate excellent follow-up of patient outcomes using text messages. Despite national guidelines, there is significant variation in practice. This data directly informed the development of an ongoing nationwide randomized clinical trial – the FORearm Fracture Recovery in Children Evaluation (FORCE) study

Aims. Whether patient-reported pain differs among surgical approaches in total hip arthroplasty (THA) remains unclear. This study’s purposes were to determine differences in pain based on surgical approach (direct anterior (DA) vs posterolateral (PL)) and PL approach incision length. . Patients and Methods. This was a retrospective investigation from two centres and seven surgeons (three DA, three PL, one both) of primary THAs. PL patients were categorized for incision length (6 cm to 8 cm, 8 cm to 12 cm, 12 cm to 15 cm). All patients had cementless femoral and acetabular fixation, at least one year’s follow-up, and well-fixed components. Patients completed a pain-drawing questionnaire identifying the location and intensity of pain on an anatomical diagram. Power analysis indicated 800 patients in each cohort for adequate power to detect a 4% difference in pain (alpha = 0.05, beta = 0.80). Results. A total of 1848 patients (982 DA, 866 PL) were included. PL patients were younger (59.4 years, . sd. 12.9 vs 62.7 years, . sd. 9.7; p < 0.001) and had shorter follow-up (3.3 years, . sd. 1.3 vs 3.7 years, . sd. 1.3; p < 0.001). DA patients reported decreased moderate to severe trochanteric (14% vs 21%; p < 0.001) and groin pain (19% vs 24%; p = 0.004) than PL patients. There were no differences in anterior, lateral, or posterior thigh, back, or buttock pain between cohorts (p = 0.05 to 0.7). PL approach incision length did not impact the incidence or severity of pain (p = 0.3 to 0.7). Conclusion. A significant proportion of patients perceive persistent pain following THA regardless of approach. DA patients reported less trochanteric and groin pain versus PL patients. PL incision length did not influence the incidence or severity of patient-reported pain. Cite this article: Bone Joint J 2019;101-B(6 Supple B):31–36

Aims. We performed a meta-analysis investigating the association between preoperative psychological distress and postoperative pain and function after total knee arthroplasty (TKA). Materials and Methods. Pubmed/Medline, Embase, PsycINFO, and the Cochrane library were searched for studies on the influence of preoperative psychological distress on postoperative pain and physical function after TKA. Two blinded reviewers screened for eligibility and assessed the risk of bias and the quality of evidence. We used random effects models to pool data for the meta-analysis. Results. Six prospective cohort studies, with a total of 1525 patients, were included. The random effects models showed significantly poorer outcomes in patients who preoperatively had elevated scores on the pain catastrophizing scale, worse 36-Item Short-Form Health Survey (SF-36) mental health score, symptoms of anxiety and/or depression, and somatization dysfunction. After 12 months, the standard mean difference for pain was −0.74 (95% confidence interval (CI) −1.04 to −0.44) and −0.56 (95% CI −0.80 to −0.32) for function. Conclusion. Preoperative pain catastrophizing, mental distress, symptoms of anxiety and/or depression, and somatoform disorders appear to adversely affect pain and function after TKA. Some patients undergoing TKA may therefore need psychological support to improve the outcome and quality of life

Aims. The aims of this study were to investigate any possible relationship between a preoperative sensitivity to pain and the degree of pain at rest and on exertion with postoperative function in patients who underwent stemless total shoulder arthroplasty (TSA). Patients and Methods. In this prospective study, we included 63 patients who underwent stemless TSA and were available for evaluation one year postoperatively. There were 31 women and 32 men; their mean age was 71 years (53 to 89). The pain threshold, which was measured using a Pain Matcher (PM) unit, the degree of pain (visual analogue scale at rest and on exertion, and function using the short version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), were recorded preoperatively, as well as three and 12 months postoperatively. Results. We found an inverse relationship between both the preoperative PM threshold and pain (VAS) at rest and the 12-month postoperative QuickDASH score (Pearson correlation coefficient (r) ≥ 0.4, p < 0.05). A linear regression analysis showed that the preoperative PM threshold on the affected side and preoperative pain (VAS) at rest were the only factors associated with the QuickDASH score at 12 months. Conclusion. These findings indicate the importance of central sensitization in the restoration of function after TSA. Further studies are required to investigate whether extra analgesia and rehabilitation could influence the outcome in at risk patients. Cite this article: Bone Joint J 2018;100-B:480–4

Objectives. In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models. Methods. OA was induced in the knee joints of male Wistar rats using transection of the ACL or induction of osteochondral injury. Changes in the percentage of high limb weight distribution (%HLWD) on the operated hind limb were used to determine the pain behaviour in these models. The development of OA was assessed and compared using a histological evaluation based on the Osteoarthritis Research Society International (OARSI) cartilage OA histopathology score. Results. Both models showed an increase in joint pain as indicated by a significant (p < 0.05) decrease in the values of %HLWD at one week post-surgery. In the osteochondral injury model, the %HLWD returned to normal within three weeks, while in the ACLT model, a significant decrease in the %HLWD was persistent over an eight-week period. In addition, OA progression was more advanced in the ACLT model than in the osteochondral injury model. Furthermore, the ACLT model exhibited a higher mean OA score than that of the osteochondral injury model at 12 weeks. Conclusion. The development of pain patterns in the ACLT and osteochondral injury models is different in that the OA progression was significant in the ACLT model. Although both can be used as models for a post-traumatic injury of the knee, the selection of appropriate models for OA in preclinical studies should be specified and relevant to the clinical scenario. Cite this article: T. Tawonsawatruk, O. Sriwatananukulkit, W. Himakhun, W. Hemstapat. Comparison of pain behaviour and osteoarthritis progression between anterior cruciate ligament transection and osteochondral injury in rat models. Bone Joint Res 2018;7:244–251. DOI: 10.1302/2046-3758.73.BJR-2017-0121.R2

We report the incidence and intensity of persistent pain in patients with an otherwise uncomplicated total ankle replacement (TAR). Arthroscopic debridement was performed in selected cases and the clinical outcome was analysed. Among 120 uncomplicated TARs, there was persistent pain with a mean visual analogue scale (VAS) of 2.7 (0 to 8). The intensity of pain decreased in 115 ankles (95.8%). Exercise or walking for more than 30 minutes was the most common aggravating factor (62 ankles, 68.1%). The character of the pain was most commonly described as dull (50 ankles, 54.9%) and located on the medial aspect of the joint (43 ankles, 47.3%). A total of seven ankles (5.8%) underwent subsequent arthroscopy. These patients had local symptoms and a VAS for pain ≥ 7 on exertion. Impingement with fibrosis and synovitis was confirmed. After debridement, the median VAS decreased from 7 to 3 and six patients were satisfied. The median VAS for pain and the American Orthopaedic Foot and Ankle Society score of the ankles after debridement was similar to that of the uncomplicated TARs (p = 0.496 and p = 0.066, respectively). Although TAR reduces the intensity of pain, residual pain is not infrequent even in otherwise uncomplicated TARs and soft-tissue impingement is the possible cause. Cite this article: Bone Joint J 2013;95-B:378–83

The purpose of this study was to establish whether exploration and neurolysis is an effective method of treating neuropathic pain in patients with a sciatic nerve palsy after total hip replacement (THR). A total of 56 patients who had undergone this surgery at our hospital between September 1999 and September 2010 were retrospectively identified. There were 42 women and 14 men with a mean age at exploration of 61.2 years (28 to 80). The sciatic nerve palsy had been sustained by 46 of the patients during a primary THR, five during a revision THR and five patients during hip resurfacing. The mean pre-operative visual analogue scale (VAS) pain score was 7.59 (2 to 10), the mean post-operative VAS was 3.77 (0 to 10), with a resulting mean improvement of 3.82 (0 to 10). The pre- and post-neurolysis VAS scores were significantly different (p < 0.001). Based on the findings of our study, we recommend this form of surgery over conservative management in patients with neuropathic pain associated with a sciatic nerve palsy after THR. Cite this article: Bone Joint J 2013;95-B:20–2

Component malalignment can be associated with pain following total knee replacement (TKR). Using MRI, we reviewed 50 patients with painful TKRs and compared them with a group of 16 asymptomatic controls to determine the feasibility of using MRI in evaluating the rotational alignment of the components. Using the additional soft-tissue detail provided by this modality, we also evaluated the extent of synovitis within these two groups. Angular measurements were based on the femoral transepicondylar axis and tibial tubercle. Between two observers, there was very high interobserver agreement in the measurements of all values. Patients with painful TKRs demonstrated statistically significant relative internal rotation of the femoral component (p = 0.030). There was relative internal rotation of the tibial to femoral component and combined excessive internal rotation of the components in symptomatic knees, although these results were significant only with one of the observers (p = 0.031). There was a statistically significant association between the presence and severity of synovitis and painful TKR (p < 0.001).

MRI is an effective modality in evaluating component rotational alignment.

Aims. The aim of this study was to describe the prevalence and patterns of neuropathic pain over one year in a cohort of patients with chronic post-surgical pain at three months following total knee arthroplasty (TKA). Methods. Between 2016 and 2019, 363 patients with troublesome pain, defined as a score of ≤ 14 on the Oxford Knee Score pain subscale, three months after TKA from eight UK NHS hospitals, were recruited into the Support and Treatment After Replacement (STAR) clinical trial. Self-reported neuropathic pain and postoperative pain was assessed at three, nine, and 15 months after surgery using the painDETECT and Douleur Neuropathique 4 (DN4) questionnaires collected by postal survey. Results. Symptoms of neuropathic pain were common among patients reporting chronic pain at three months post-TKA, with half reporting neuropathic pain on painDETECT (191/363; 53%) and 74% (267/359) on DN4. Of those with neuropathic pain at three months, half continued to have symptoms over the next 12 months (148/262; 56%), one-quarter had improved (67/262; 26%), and for one-tenth their neuropathic symptoms fluctuated over time (24/262; 9%). However, a subgroup of participants reported new, late onset neuropathic symptoms (23/262; 9%). Prevalence of neuropathic symptoms was similar between the screening tools when the lower cut-off painDETECT score (≥ 13) was applied. Overall, mean neuropathic pain scores improved between three and 15 months after TKA. Conclusion. Neuropathic pain is common in patients with chronic pain at three months after TKA. Although neuropathic symptoms improved over time, up to half continued to report painful neuropathic symptoms at 15 months after TKA. Postoperative care should include screening, assessment, and treatment of neuropathic pain in patients with early chronic postoperative pain after TKA. Cite this article: Bone Joint J 2024;106-B(6):582–588

Abstract. Introduction. Total knee replacement (TKR) is a successful operation for many patients, however 15–20% of patients experience chronic post-surgical pain (CPSP). Many will experience neuropathic characteristics. We describe the prevalence and patterns of neuropathic pain in a cohort of patients with CPSP three months after TKR. Methodology. Between 2016–2019, 363 patients with troublesome pain, ≤14 on Oxford Knee score pain subscale, at three months after TKR from eight NHS hospitals were recruited into the Support and Treatment After Replacement (STAR) trial. Self-reported neuropathic pain was assessed at three, nine and fifteen months after surgery using painDETECT and Douleur Neuropathique 4 (DN4). Results. At three months post-operative, 53% reported neuropathic pain on painDETECT and 74% on DN4. Half (56%) remained in neuropathic pain over the twelve-month follow-up period, 26% reported improvement, and 9% reported new neuropathic symtpoms or fluctuated in and out of neuropathic pain (9%). Overall mean neuropathic pain scores improved between three and 15 months after TKR. When the painDETECT cut-off score of ≥13(ambiguous/possible) was used, DN4 and painDETECT measures showed similar prevalence rates at each timepoint. Conclusion. Neuropathic pain is common among patients with CPSP at three months after TKR. Although symptoms improved over time, one quarter to one half of our cohort continued to report symptoms at fifteen months. We propose a painDETECT cutoff score of ≥13 be used to identify neuropathic features in the TKR population. Postoperative care should include identification, assessment, and treatment of neuropathic pain in patients with CPSP after TKR

Background. Low back pain can lead to neuroplastic changes in the central nervous system, known as nociplastic pain. As nociplastic pain may be provoked by premorbid sensory profiles, such profiles may be prognostic in the development of nociplastic pain over time. Objectives. To investigate whether four sensory profiles are prognostic in the development of symptoms of nociplastic pain in people with acute low back pain. Methods. A longitudinal type 2 prognostic factor research study was performed in accordance with the PROGRESS framework, using a baseline and a follow-up after 12 weeks, between the Adolescent/Adult Sensory Profile and the Central Sensitisation Inventory. Study participants were consecutively included from primary care physiotherapy practices randomly spread throughout the Netherlands. A multivariable regression analysis was performed to adjust sensory profiles by the level of pain, disability, age, and duration of low back pain. Results. After adjustment Low Registration B=0.41, 95%CI (0.37, 0.99), Sensory Seeking B=0.37, 95%CI (0.24, 0.73), Sensory Sensitive B=0.51, 95%CI (0.50, 1.06), Sensation Avoiding B=0.46, 95%CI (0.43, 0.99) were significantly associated with the development of nociplastic pain symptoms. Conclusion. Sensory profiles in people with acute low back pain predict symptoms of nociplastic pain after 12 weeks. Conflict of interest: No conflict of interest. Sources of funding: No funding obtained

Aims. The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold. Methods. Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency. Results. IBA1 and cyclin D1 in the ipsilateral spinal horn increased in a time-dependent fashion. Spinal microglia proliferated in BCP rats. The microglia inhibitor minocycline attenuated the pain behaviour in BCP rats. The cyclin-dependent kinase inhibitor flavopiridol inhibited the proliferation of spinal microglia, and was associated with an improvement in pain behaviour in BCP rats. Conclusion. Our results revealed that the inhibition of spinal microglial proliferation was associated with a decrease in pain behaviour in a rat model of BCP. Cyclin D1 acts as a key regulator of the proliferation of spinal microglia in a rat model of BCP. Disruption of cyclin D1, the restriction-point control of cell cycle, inhibited the proliferation of microglia and attenuated the pain behaviours in BCP rats. Cyclin D1 and the proliferation of spinal microglia may be potential targets for the clinical treatment of BCP. Cite this article: Bone Joint Res 2022;11(11):803–813

Aims. Despite new technologies for total knee arthroplasty (TKA), approximately 20% of patients are dissatisfied. A major reason for dissatisfaction and revision surgery after TKA is persistent pain. The radiological grade of osteoarthritis (OA) preoperatively has been investigated as a predictor of the outcome after TKA, with conflicting results. The aim of this study was to determine if there is a difference in the intensity of pain 12 months after TKA in relation to the preoperative radiological grade of OA alone, and the combination of the intensity of preoperative pain and radiological grade of OA. Methods. The preoperative data of 300 patients who underwent primary TKA were collected, including clinical information (age, sex, preoperative pain), psychological variables (depression, anxiety, pain catastrophizing, anticipated pain), and quantitative sensory testing (temporal summation, pressure pain thresholds, conditioned pain modulation). The preoperative radiological severity of OA was graded according to the Kellgren-Lawrence (KL) classification. Persistent pain in the knee was recorded 12 months postoperatively. Generalized linear models explored differences in postoperative pain according to the KL grade, and combined preoperative pain and KL grade. Relative risk models explored which preoperative variables were associated with the high preoperative pain/low KL grade group. Results. Pain 12 months after TKA was not associated with the preoperative KL grade alone. Significantly increased pain 12 months after TKA was found in patients with a combination of high preoperative pain and a low KL grade (p = 0.012). Patients in this group were significantly more likely to be male, younger, and have higher preoperative pain catastrophizing, higher depression, and lower anxiety (all p ≤ 0.05). Conclusion. Combined high preoperative pain and low radiological grade of OA, but not the radiological grade alone, was associated with a higher intensity of pain 12 months after primary TKA. This group may have a more complex cause of pain that requires additional psychological interventions in order to optimize the outcome of TKA. Cite this article: Bone Joint J 2022;104-B(11):1202–1208

Background. The association between lumbar intervertebral disc degeneration (LDD) and low back pain (LBP) is modest. We have recently shown that genetic propensity to pain is an effect modifier of the LDD-LBP relationship when LDD is defined as a summary score of LDD (LSUM), suggesting the association may be driven by individuals with the greatest genetic predisposition to pain. This study examined the association between individual spine magnetic resonance imaging (MRI)-determined LDD features and LBP in subgroups defined by genetic predisposition to pain. Method. We developed a polygenic risk score (PRS) for “genetic propensity to pain” defined as the number of non-back pain locations (head, face, neck/shoulder, stomach/abdomen, hip, and knee) with duration ≥3 months in 377,538 UK Biobank participants of European ancestry. This PRS was used to stratify TwinsUK MRI samples (n=645) into four strata of genetic propensity to pain. We examined the association between LBP and MRI features of lumbar disc height, disc signal intensity, disc bulge, and osteophytes with adjustments for age, sex, PRS strata, interaction terms for each MRI feature x PRS strata, and twin status. Results. We found significant effect modification of the LDD-LBP relationship by genetic propensity to pain for the lumbar MRI features of disc height (p=0.03 for the interaction term with highest quartile of genetically-predicted propensity to pain) and disc signal intensity (p=0.001), but not for disc bulge and osteophytes. Conclusion. Genetic propensity to pain modifies the association between individual LDD features and LBP and should be considered in LBP clinical studies. Conflicts of interest. No conflicts of interest. Sources of funding. No funding obtained. Acknowledgement. UKBB data were obtained under the project #18219. This paper is submitted to the Spine journal and is under review