Strength training in addition to neuromuscular exercise and education in individuals with knee osteoarthritis-the effects on pain and sensitization.

BACKGROUND: There is a lack of evidence of the relative effects of different exercise modes on pain sensitization and pain intensity in individuals with knee osteoarthritis (KOA). METHODS: Ninety individuals with radiographic and symptomatic KOA, ineligible for knee replacement surgery, were randomized to 12 weeks of twice-weekly strength training in addition to neuromuscular exercise and education (ST+NEMEX-EDU) or neuromuscular exercise and education alone (NEMEX-EDU). Outcomes were bilateral, lower-leg, cuff pressure pain- and tolerance thresholds (PPT, PTT), temporal summation (TS), conditioned pain modulation (CPM), self-reported knee pain intensity and number of painful body sites. RESULTS: After 12 weeks of exercise, we found significant differences in increases in PPT (-5.01 kPa (-8.29 to -1.73, p = .0028)) and PTT (-8.02 kPa (-12.22 to -3.82, p = .0002)) in the KOA leg in favour of ST+NEMEX-EDU. We found no difference in effects between groups on TS, CPM or number of painful body sites. In contrast, there were significantly greater pain-relieving effects on VAS mean knee pain during the last week (-8.4 mm (-16.2 to -0.5, p = .0364) and during function (-16.0 mm (-24.8 to -7.3, p = .0004)) in favour of NEMEX-EDU after 12 weeks of exercise. CONCLUSION: Additional strength training reduced pain sensitization compared to neuromuscular exercise and education alone, but also attenuated the reduction in pain intensity compared to neuromuscular exercise and education alone. The study provides the first dose- and type-specific insight into the effects of a sustained exercise period on pain sensitization in KOA. Future studies are needed to elucidate the role of different exercise modes. SIGNIFICANCE: This study is an important step towards better understanding the effects of exercise in pain management of chronic musculoskeletal conditions. We found that strength training in addition to neuromuscular exercise and education compared with neuromuscular exercise and education only had a differential impact on pain sensitization and pain intensity, but also that regardless of the exercise mode, the positive effects on pain sensitization and pain intensity were comparable to the effects of other therapeutic interventions for individuals with knee osteoarthritis.

Patients With High Chronic Postoperative Knee Pain 5 Years After Total Knee Replacement Demonstrate Low-grad Inflammation, Impairment of Function, and High Levels of Pain Catastrophizing.

OBJECTIVES: Total knee replacement (TKR) normally provides improvements of physical function and reduces pain. However, ∼20% of the patients report chronic postoperative knee pain. The aims of the present study were to assess the pain, physical function, and physiological characteristics 5 years after TKR surgery. MATERIALS AND METHODS: Eighty patients were recruited 5 years after TKR and divided into 2 groups based on their average 24-hour knee pain intensity assessed on a visual analog scale (VAS 0 to 10) ("high pain group": VAS≥3; "low pain group": VAS<3). The patients completed the PainDETECT Questionnaire (PDQ), Oxford Knee Score (OKS), Pain Catastrophizing Scale, and Forgotten Joint Score-12. Furthermore, the patients underwent a clinical examination of the knees and high-sensitivity serum C-reactive protein was measured as an inflammatory marker. RESULTS: A total of 53% of the patients in the high pain group were not satisfied with the outcome, while only 11% of the patients in the low pain group was not satisfied, and the pain intensities in the 2 groups were 5.1 (4.6 to 5 to 6) and 1.1 (0.6 to 1.5) (P<0.001), respectively. Furthermore, the high pain group demonstrates worse scores in: Forgotten Joint Score-12 (P=0.001), OKS function (P<0.001), OKS pain (P<0.001), and Pain Catastrophizing Scale (P<0.001).The high pain group demonstrated increased level of high-sensitivity serum C-reactive protein (4.3 mg/L [3.2 to 5.5] vs. 1.7 mg/L [1.2 to 2.2], P<0.001), and decreased range of motion in the knee (110 vs. 119-degree range of motion, P=0.013). DISCUSSION: Patients with high chronic postoperative knee pain 5 years after TKR demonstrate decreased physical function, higher levels of catastrophizing thoughts, and increased levels of inflammation.

Chronic Postoperative Pain After Hysterectomy for Endometrial Cancer: A Metabolic Profiling Study.

INTRODUCTION: One out of seven women will develop a state of chronic postoperative pain following robot-assisted hysterectomy for endometrial cancer. Recently, metabolic studies have indicated that circulating lipids and lipoproteins could act as nociceptive modulators and thereby influence the induction and perpetuation of pain. The objectives of this explorative study were (1) to examine the preoperative serologic variations in concentrations of lipids, lipoproteins, and various low-molecular metabolites in patients with and without chronic postoperative pain after robot-assisted hysterectomy and (2) to explore if any of these serological biomarkers were predictive for development of chronic postoperative pain. MATERIALS AND METHODS: The study was designed as a nested case-control study within a cohort of women treated for endometrial cancer with robot-assisted laparoscopic hysterectomy. Twenty-six women with chronic postoperative pain were matched on age and body mass index with fifty-two controls without chronic postoperative pain, and metabolic profiling of preoperatively drawn blood samples from a biobank was performed by means of nuclear magnetic resonance spectroscopy. RESULTS: Nineteen metabolites, including cholesterol, cholesteryl ester, linoleic acid, phospholipids, lipids, and triglycerides had statistically significant higher concentrations in a subgroup of patients who would develop chronic postoperative pain on a later stage compared to the group of patients who would not develop chronic postoperative pain (p < 0.05). A sparse Partial Least Squares-Discriminant Analysis model explained 38.1% of the variance and had a predictive accuracy of 73.1%. CONCLUSIONS: This explorative study substantiates the hypothesis that certain lipids, lipoproteins, and fatty acids are associated with chronic postoperative pain.

Investigating the Effect of Perioperative Chlorzoxazone on Acute Postoperative Pain After Total Hip and Knee Replacement Surgery.

BACKGROUND AND AIMS: Severe preoperative and acute postoperative pain have been associated with the development of chronic postoperative pain. Chlorzoxazone (a muscle relaxant) has been suggested to enhance acute postoperative pain recovery, but the lack of larger randomized controlled trials has, however, questioned the continued use. Despite this, chlorzoxazone is still used for acute postoperative pain management following total knee replacement (TKR) or total hip replacement (THR). The current randomized, double-blinded, placebo-controlled, parallel-group, clinical trial aimed to assess the effect of chlorzoxazone for postoperative pain management following TKR or THR. METHODS: A total of 393 patients scheduled for TKR or THR were included in the trial. Patients were assigned to 250 mg chlorzoxazone 3 times daily for the first 7 days postoperatively or to placebo. The primary outcome was pain after 5 m walk assessed 24 hours postoperatively. Secondary outcomes included changes in preoperative pain at rest, worst pain in the last 24 hours, and Oxford Knee or Hip Score compared with 12 months' follow-up. In addition, adverse events were assessed in the perioperative period. RESULTS: No significant differences were found for any of the outcome parameters after TKR or THR. As regards TKR or THR, no effects were demonstrated for pain after 5 m walk 24 hours after surgery (P>0.313), or for any of the secondary outcomes (P>0.288) or adverse events (P>0.112) in the group receiving chlorzoxazone compared with placebo. CONCLUSION: The current study demonstrated no analgesic effects of postoperative chlorzoxazone administration compared with placebo on acute or chronic postoperative pain 12 months following TKR and THR.

Serum Inflammatory Markers in Patients With Knee Osteoarthritis: A Proteomic Approach.

OBJECTIVES: Osteoarthritis (OA) is known to be a slowly progressive disease that alters all tissue compartments of the joint involved with a characteristic degradation of the cartilage, bone remodeling, and inflammation. One of the prominent symptoms in OA patients is pain, but a few radiologic, inflammatory, or structurally related biomarkers have shown few if any associations with pain. This study aimed to assess serum levels of 92 markers involved in inflammatory pathways in patients with knee osteoarthritis (KOA) and evaluate their possible associations with the clinical pain intensity. MATERIALS AND METHODS: Serum samples were collected from 127 KOA patients and 39 healthy participants with no knee pain. Each serum sample was analyzed for 92 inflammatory markers using the Proximity Extension Array (PEA) technology. Clinical pain intensity was assessed using a Visual Analog Scale, and patients completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. RESULTS: Fifteen markers were significantly different when comparing KOA patients and healthy participants. Two markers, fibroblast growth factor-21 and Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), correlated positively with pain intensity (R=0.235, P=0.008; R=0.233, P=0.008). Moreover, a linear regression model showed interleukin-6, macrophage colony-stimulating factor 1, fibroblast growth factor-21, and tumor necrosis factor superfamily member 12 (TWEAK) as significant independent parameters for pain intensity. DISCUSSION: The associations between specific cytokines and KOA pain intensities provide new insights into the understanding of the underlying factors driving the pain in OA.

Presurgical Comorbidities as Risk Factors For Chronic Postsurgical Pain Following Total Knee Replacement.

OBJECTIVES: Chronic postsurgical knee pain (CPSP) is a burden for ∼20% of the patients following total knee replacement (TKR). Presurgical pain intensities have consistently been found associated with CPSP, and it is suggested that comorbidities are likewise important for the development of CPSP. This study aimed to identify presurgical risk factors for the development of CPSP 5 years after TKR on the basis of medical records containing information with regard to comorbidities. MATERIALS AND METHODS: Patients undergoing primary TKR surgery were contacted 5 years after TKR. Presurgical Knee Society Score and comorbidities were evaluated. Postsurgical knee pain at 5 years of follow-up was assessed on a Numeric Rating Scale (NRS, 0 to 10). Logistic regression models were utilized to identify patients with moderate-to-severe (NRS≥3) and mild-to-no (NRS<3) CPSP at 5-year follow-up. Odds ratio (OR) for significant factors was calculated. RESULTS: A total of 604 patients were contacted, 493 patients responded, 352 patients provided a completed questionnaire. A total of 107 patients reported NRS≥3 at follow-up. Significant presurgical factors associated with CPSP were fibromyalgia (OR=20.66; P=0.024), chronic pain in body parts other than the knee (OR=6.70; P=0.033), previous diagnosis of cancer (OR=3.06; P=0.001), knee instability (OR=2.16; P=0.021), younger age (OR=2.15; P=0.007), and presurgical knee pain (OR=1.61; P=0.044). Regression analysis identified 36 of 107 (33.6%) patients with CPSP on the basis of presurgical factors, and 231 patients (94.3%) without CPSP were classified correctly. DISCUSSION: The current study found that a variety of presurgical clinical factors can correctly classify 33.6% of patients at risk for developing CPSP 5 years following TKR.

Preoperative Neuropathic Pain-like Symptoms and Central Pain Mechanisms in Knee Osteoarthritis Predicts Poor Outcome 6 Months After Total Knee Replacement Surgery.

Preoperative pain characteristics in patients with osteoarthritis may explain persistent pain after total knee replacement. Fifty patients awaiting total knee replacement and 22 asymptomatic controls were recruited to evaluate the degree of neuropathic pain symptoms and pain sensitization. Patients with OA were pain phenotyped into 2 groups based on the PainDETECT questionnaire: high PainDETECT group (scores ≥19) indicating neuropathic pain-like symptoms and low PainDETECT group (scores <19) indicating nociceptive or mixed pain. Cuff algometry assessing pain detection thresholds and pain tolerance thresholds was conducted on the lower legs. Temporal summation of pain was assessed using 10 sequential cuff stimulations and a von Frey stimulator. Conditioning pain modulation was assessed by cuff pain conditioning on 1 leg and parallel assessment of pain detection thresholds on the contralateral leg. Pressure pain thresholds were recorded by pressure handheld algometry local and distant to the knee. Knee pain intensity (visual analogue scale) and pain assessments were collected before and 6 months after total knee replacement. Thirty percent of patients demonstrated neuropathic pain-like symptoms (high PainDETECT group). Facilitated temporal summation of pain and reduced pressure pain thresholds distant to the knee were found in the high PainDETECT group compared with the low PainDETECT group and healthy controls (P < .001). Patients with OA with high PainDETECT scores had higher postoperative visual analogue scale pain scores than the low PainDETECT patients (P < .0001) and facilitated temporal summation of pain (P = .022) compared with healthy control subjects. Perspective: This study has found that preoperative PainDETECT scores independently predict postoperative pain. Patients with knee OA with neuropathic pain-like symptoms identified using the PainDETECT questionnaire are most at risk of developing chronic postoperative pain after TKR surgery.

Chronic postoperative pain after primary and revision total knee arthroplasty.

OBJECTIVES: Clinical experience suggests that patients with osteoarthritis (OA) undergoing revision total knee arthroplasty (TKA) experience more chronic complications after surgery compared with patients receiving primary TKA. This study aimed to investigate the difference in pain, mobility, and quality of life (QoL) in patients after revision TKA compared with patients after primary TKA. METHODS: A total of 99 OA patients after revision TKA surgery and 215 patients after primary TKA surgery were investigated in a cross-sectional study using: a pain description of current pain (non-existent, mild, moderate, severe, or unbearable), the pain intensity visual analogue scale, the Knee Society Score, and the Osteoarthritis Research Society International questionnaire. RESULTS: Nineteen percent after primary TKA surgery and 47% after revision TKA surgery experienced severe to unbearable chronic postoperative pain. After revision TKA surgery patients reported higher pain intensities during rest (P=0.039), while walking (P=0.008), and on average over the last 24 hours (P=0.050) compared with the patients after primary TKA surgery. Patients after revision TKA surgery had reduced walking distance (P=0.001), increased use of walking aids (P=0.015), and showed an overall decreased QoL (P<0.001) compared with patients after primary TKA surgery. No significant improvement was found in walking distance (P=0.448) for patients before revision TKA surgery compared with after revision TKA surgery. DISCUSSION: More than twice as many patients have pain after revision surgery compared with patients after primary TKA. Patients after revision TKA surgery have reduced function, poorer QoL, and higher pain intensity compared with patients after primary TKA surgery.