An introduction to low dose radiation therapy for shoulder osteoarthritis.

Osteoarthritis (OA) is a painful, degenerative disease that affects the tissues of the joint spaces, such as the shoulder. Conventional medical treatment options, such as corticosteroid injections and anti-inflammatory medications, are not always sufficient to alleviate the symptoms from this disease. Low dose radiotherapy is a newer treatment option for patients with shoulder osteoarthritis and has shown positive outcomes. However, the problem is that there is a paucity of literature about treatment planning considerations for this new treatment option. The purpose of this case study was to provide an example of treatment planning techniques and considerations for shoulder osteoarthritis. Treatment techniques for shoulder LDRT, such as treatment field borders, prescribed dose, beam arrangements, appropriate beam energy, and special considerations are discussed.

ArthroRad trial: randomized multicenter single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis-final results after 12-month follow-up.

OBJECTIVE: Updated report about the randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard dose vs. a very low dose regime after a follow-up of 1 year. PATIENTS AND METHODS: Patients presenting with OA of the hand/finger and knee joints were included. After randomization (every joint region was randomized separately) the following protocols were applied: (a) standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice a week; (b) experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice a week. The dosage was blinded for the patients. For evaluation the scores after 1­year visual analog scale (VAS), Knee Injury and Osteoarthritis Outcome Score-Short Form (KOOS-PS), Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH) and 12-item Short-Form Health Survey (SF-12) were used (for further details: see [1]). RESULTS: The standard dose was applied to 77 hands and 33 knees, the experimental dose was given to 81 hands and 30 knees. After 12 months, the data of 128 hands and 45 knees were available for evaluation. Even after this long time, we observed a favorable response of pain to radiotherapy in both trial arms; however, there were no reasonable statistically significant differences between both arms concerning pain, functional, and quality of life scores. Side effects did not occur. The only prognostic factor was the pain level before radiotherapy. CONCLUSIONS: We found a favorable pain relief and a limited response in the functional and quality of life scores in both treatment arms. The possible effect of low doses such as 0.3 Gy on pain is widely unknown.

The Mechanisms and Efficacy of Photobiomodulation Therapy for Arthritis: A Comprehensive Review.

Rheumatoid arthritis (RA) and osteoarthritis (OA) have a significant impact on the quality of life of patients around the world, causing significant pain and disability. Furthermore, the drugs used to treat these conditions frequently have side effects that add to the patient's burden. Photobiomodulation (PBM) has emerged as a promising treatment approach in recent years. PBM effectively reduces inflammation by utilizing near-infrared light emitted by lasers or LEDs. In contrast to photothermal effects, PBM causes a photobiological response in cells, which regulates their functional response to light and reduces inflammation. PBM's anti-inflammatory properties and beneficial effects in arthritis treatment have been reported in numerous studies, including animal experiments and clinical trials. PBM's effectiveness in arthritis treatment has been extensively researched in arthritis-specific cells. Despite the positive results of PBM treatment, questions about specific parameters such as wavelength, dose, power density, irradiation time, and treatment site remain. The goal of this comprehensive review is to systematically summarize the mechanisms of PBM in arthritis treatment, the development of animal arthritis models, and the anti-inflammatory and joint function recovery effects seen in these models. The review also goes over the evaluation methods used in clinical trials. Overall, this review provides valuable insights for researchers investigating PBM treatment for arthritis, providing important references for parameters, model techniques, and evaluation methods in future studies.

Low-dose radiotherapy of osteoarthritis: from biological findings to clinical effects-challenges for future studies.

Osteoarthritis (OA) is one of the most common and socioeconomically relevant diseases, with rising incidence and prevalence especially with regard to an ageing population in the Western world. Over the decades, the scientific perception of OA has shifted from a simple degeneration of cartilage and bone to a multifactorial disease involving various cell types and immunomodulatory factors. Despite a wide range of conventional treatment modalities available, a significant proportion of patients remain treatment refractory. Low-dose radiotherapy (LDRT) has been used for decades in the treatment of patients with inflammatory and/or degenerative diseases and has proven a viable option even in cohorts of patients with a rather poor prognosis. While its justification mainly derives from a vast body of empirical evidence, prospective randomized trials have until now failed to prove the effectiveness of LDRT. Nevertheless, over the decades, adaptions of LDRT treatment modalities have evolved using lower dosages with establishment of different treatment schedules for which definitive clinical proof is still pending. Preclinical research has revealed that the immune system is modulated by LDRT and very recently osteoimmunological mechanisms have been described. Future studies and investigations further elucidating the underlying mechanisms are an essential key to clarify the optimal patient stratification and treatment procedure, considering the patients' inflammatory status, age, and sex. The present review aims not only to present clinical and preclinical knowledge about the mechanistic and beneficial effects of LDRT, but also to emphasize topics that will need to be addressed in future studies. Further, a concise overview of the current status of the underlying radiobiological knowledge of LDRT for clinicians is given, while seeking to stimulate further translational research.

A Case Series of 11 Horses Diagnosed with Bone Spavin Treated with High Intensity Laser Therapy (HILT).

The aim of this work was to characterize and describe the effect of High Intensity Laser Therapy (HILT) used in the treatment of chronic osteoarthritis in horses. Over a 2 year period, 11 horses with diagnosed bone spavin were treated with HILT as a monotherapy. The horses chosen for this report presented hind limb lameness, were positive in a spavin flexion test and showed improvement after intra-articular anesthesia of the tarsometatarsal joint. Additionally, all the horses presented radiological signs of tarsus osteoarthritis and had not been treated for bone spavin for a minimum of 6 months. Each horse received 10 HILT therapies over 14 days' treatment time with the same laser protocol. At post-treatment orthopedic examination, 4 horses (36%) had improved 2 lameness grades (in the 5 grade American Association of Equine practitioners lameness scale), 4 horses (36%) had improved 1 lameness grade and 3 horses (28%) did not improve. Additionally, 3 horses were totally sound after HILT. Post-treatment spavin test result improvement was observed in 5 horses (45%), and 6 horses (55%) showed the same spavin test grade as before treatment. There were no horses that were sound in the spavin test performed after HILT. Therefore, it seems probable that the application of HILT in horses suffering from bone spavin may decrease joint pain, which influences visual lameness reduction.

Intra-articular Treatment of Digital Osteoarthritis by Radiosynoviorthesis-Clinical Outcome in Long-term Follow-up.

PURPOSE: This retrospective study analyzed the long-term effects of radiosynoviorthesis (RSO) with special emphasis to local joint pain in patients from 4 different RSO centers in Germany and Austria. METHODS: A total of 168 finger joints in 147 patients with digital joint OA were investigated. The indication for RSO was based on both clinical complaints and a proven synovitis, despite anti-inflammatory pharmacotherapy and previous intra-articular corticosteroid injections. Radiosynoviorthesis was performed according to international guidelines. A numeric visual analog scale (VAS) before and after treatment was used to measure the outcome. Follow-up was done for at least 2 years after treatment, in some patients even over 10 years. RESULTS: Radiosynoviorthesis resulted in a significant reduction of VAS values in most of the patients, lasting for the whole period of follow-up. Two-thirds of the treated joints showed clinically relevant improvement, if a reduction of 30% in VAS values was defined as a reasonable cutoff. The best results were achieved in thumb base joints. CONCLUSIONS: This article confirms that RSO is a suitable treatment option for digital joint OA with a proven synovitis. The analgesic effect is long-lasting and comparable to the success of RSO in patients with rheumatoid arthritis.

The Use of Low-Dose Radiation Therapy in Osteoarthritis: A Review.

Despite its clinical use and investigation in other countries, low dose radiation therapy (LDRT) in the treatment of osteoarthritis (OA) is minimally used in the United States (US). Numerous recent studies published outside the US have shown moderate to long-term pain relief and improvement of mobility after treatment with LDRT for joints affected by OA. Here, we review the most recent literature published on the use of LDRT in OA. We provide a brief outline on the epidemiology, pathophysiology, current treatments, and health care burden of OA within the US. We provide a brief history of the historic use of LDRT in the US as well as a history of LDRT within the modern era of radiation oncology, discuss criticisms of LDRT including recently published randomized trials questioning its benefit as well as the risk of secondary malignancy from LDRT, and provide an outline of treatment planning considerations and recommendations regarding dose and fractionation, energy, beam arrangements, and immobilization techniques. LDRT has been shown to be a cost-effective, noninvasive treatment with minimal side effects. Further investigation into the potential role in the treatment of OA with modern LDRT is recommended.

External Radiation Dose to Owners of Canines Treated with ( 117m Sn) Radiosynoviorthesis for Osteoarthritis.

ABSTRACT: A novel device in the veterinary market uses a colloid containing radioactive 117m Sn to treat osteoarthritis in the synovial joints of canines. The technique of injecting a radioisotope to restore synovia is referred to as radiosynoviorthesis. The outpatient canine procedure uses a maximum administration of 222 MBq of 117m Sn injected into one or more joints. Due to the 13.91 d half-life and 158.6 keV gamma output of 117m Sn, abiding by the annual public dose limit of 1 mSv is of primary regulatory concern. The therapy protocol starts with a pre-screening questionnaire to establish owner and animal behavior patterns. The questionnaire is used to determine the duration of written time and distance limitations post therapy. In this study, external radiation doses to owners were measured by providing optically stimulated luminescent dosimeters (OSLD) for up to 30 d post-treatment of the pet. Twelve owners were measured over various time frames at two licensed locations independent of each other. In one location, the average (OSLD) measured 0.029 mSv over a 14-d wear period. In the second location, the average (OSLD) measured 0.057 mSv over a 30-d wear period; both values were well below the recommended annual public dose. The overall average extrapolated external radiation dose was estimated at 0.092 mSv, while the maximum dose estimate was 0.25 mSv. The (OSLD) results and extrapolated owner doses provide reasonable assurance that the public dose limits will be met.

ArthroRad trial: multicentric prospective and randomized single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis depending on the dose-results after 3 months' follow-up.

PURPOSE: Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime PATIENTS AND METHODS: Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used. RESULTS: A total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment. CONCLUSION: We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders.

Low-dose radiation therapy for hand osteoarthritis: shaking hands again?

BACKGROUND: Hand osteoarthritis (HOA) is one of the most common causes of pain and functional disability in western countries and there is still no definitive cure. Low-dose radiation therapy (LDRT) has anti-inflammatory properties that have shown to be effective in the symptomatic relief of various degenerative musculoskeletal disorders. We designed a clinical protocol using LDRT for symptomatic HOA and present results and tolerance in the first 100 patients included. MATERIALS AND METHODS: Between April 2015 and March 2021, 100 patients with a median age of 60 were treated. Fifty-seven patients suffering from proximal/distal interphalangeal joint pain, 40 patients with thumb arthritis, 2 patients with radiocarpal joint affection and 1 patient with metacarpophalangeal joint pain were enrolled. LDRT comprised of 6 fractions of 0.5-1 Gy on every other day up to a total dose of 3-6 Gy. Clinical response was evaluated according to the visual analog scale (VAS) for pain level and the von Pannewitz score (VPS) for joint functionality. Any patients not achieving subjective adequate pain relief after 8 weeks of treatment were offered a second identical LDRT course. RESULTS: With a median follow-up of 10.5 months (range 7.55-12.45), 94% reported an improvement in the pain, with a significant reduction in the VAS level after 3, 6 and 12 months (p < 0.001). Sixty-three patients needed a second course of treatment at a median time interval of 12 weeks (range 9-14). The mean VAS score before treatment was 8 (range 3-10). After treatment, it was 5 (range 1-10). After 3, 6 and 12 months, the mean VAS scores were 4 (range 0-9), 3 (range 0-9) and 3.5 (range 0-9), respectively. Seventy patients reported functionality improvements after LDRT according to the von Pannewitz score. No acute or late complications were observed. CONCLUSION: LDRT appears to be safe and useful for HOA and is associated with good rates of pain relief and functionality improvements. However, further studies are necessary to confirm these promising results.

Investigation of the effects of therapeutic ultrasound or photobiomodulation and the role of spinal glial cells in osteoarthritis-induced nociception in mice.

Pain is the most common symptom of osteoarthritis, and spinal glia is known to contribute to this symptom. Therapeutic ultrasound and laser therapy have been used to effectively treat osteoarthritis, with few adverse effects. Thus, this study aimed to investigate the effects of ultrasound and photobiomodulation on the symptoms and evaluate the participation of spinal glia in osteoarthritis-induced nociception in mice. Male Swiss mice were subjected to osteoarthritis induction with a 0.1-mg intra-articular injection of monosodium iodoacetate. Additionally, the mice received chronic ultrasound or photobiomodulation treatment for 21 days or a single treatment at day 14. Nociception was evaluated using von Frey filaments, and osteoarthritis symptoms were assessed by analysis of gait, joint temperature, and knee joint diameter. The role of spinal microglia and astrocytes on nociception was evaluated via an intrathecal injection of minocycline or fluorocitrate, and the spinal release of IL-1ß and TNF-α was assessed by ELISA after chronic treatment with ultrasound or photobiomodulation. Our data showed that both single and chronic treatment with ultrasound or photobiomodulation attenuated the osteoarthritis-induced nociception. No differences in gait, knee joint temperature, or knee joint diameter were found. The intrathecal injection of minocycline and fluorocitrate decreased the osteoarthritis-induced nociception. There was an increase in the spinal levels of TNF-α, which was reverted by chronic ultrasound and laser treatments. These results suggest that osteoarthritis induces nociception and glial activation via spinal release of TNF-α and that the chronic treatment with ultrasound or photobiomodulation decreased nociception and TNF-α release.

Effects of photobiomodulation therapy in chondrocyte response by in vitro experiments and experimental model of osteoarthritis in the knee of rats.

The purpose of this study is to evaluate the effects of photobiomodulation (PBM) therapy in chondrocyte response by in vitro experiments and cartilage repair using an experimental model of osteoarthritis (OA) in the knee of rats. The in vitro experiment was performed with chondrocyte cells, and they were divided into two groups: non-irradiated and irradiated with PBM (808 nm; 0.8 J or 1.4 J). Then, cell proliferation was evaluated after 1, 3, and 5 days. The experimental model of osteoarthritis (OA) was performed in the knee of 64 Wistar rats, and they were assorted into control group (CG), PBM (808 nm; 1.4 J). The results of in vitro showed that PBM 1.4 J increased cell proliferation, on days 1 and 5. However, after 3 days was demonstrated a significant increase in cell proliferation in PBM 0.8 J. The in vivo experiment results demonstrated, on histological analysis, that PBM presented less intense signs of tissue degradation with an initial surface discontinuity at the superficial zone and disorganization of the chondrocytes in the cartilage region when compared to CG, after 4 and 8 weeks. These findings were confirmed by immunohistochemistry and qRT-PCR analysis which showed that PBM increased IL-4, IL-10, COL-2, Aggrecan, and TGF-ß which are anabolic factors and acts on extracellular matrix. Also, PBM reduces the IL1-ß, an inflammatory marker that operates as a catabolic factor on articular cartilage. In conclusion, these results suggest that PBM may have led to a return to tissue homeostasis, promoting chondroprotective effects and stimulating the components of the articular tissue.

Prospective Evaluation of Low-Dose External Beam Radiotherapy (LD-EBRT) for Painful Trapeziometacarpal Osteoarthritis (Rhizarthrosis) on Pain, Function, and Quality of Life to Calculate the Required Number of Patients for a Prospective Randomized Study.

Background: Retrospective studies have described the effectiveness of low-dose radiotherapy (LD-EBRT) in painful arthrosis of small finger joints, but two recent prospective studies have yielded ambiguous results. To generate accurate data for the planning of a trial, we conducted a prospective, monocentric, observational study to describe the effects of LD-EBRT as precisely as possible. Methods: Twenty-five consecutive patients with symptomatic trapeziometacarpal (TMC) arthrosis were irradiated with 6 × 0.5 Gy. Before, 3, and 12 months after LD-EBRT, we assessed subjective endpoints (modified "von-Pannewitz score", 10-point visual analogue scale (VAS), "patient-rated wrist evaluation" (PRWE)), and objective measurements ("active range of motion" (AROM), Kapandji index, grip strength, pinch grip). Results: At 3/12 months, 80%/57% reported partial and 4%/18% complete remission according to the "von-Pannewitz" score. VAS "overall pain" significantly decreased from a median of seven (IQR 4) at baseline to three (IQR 6; p = 0.046) and to two (IQR 2; p = 0.013). Similar results were obtained for VAS "pain during exercise", VAS "pain during daytime", and VAS "function". "PRWE overall score" was reduced from 0.5 at baseline (SD 0.19) to 0.36 (SD 0.24, p = 0.05) and to 0.27 (SD 0.18, p = 0.0009). We found no improvements of the objective endpoints (AROM, Kapandji, grip strength) except for flexion, which increased from 64° (SD 12°) at baseline to 73° (SD 9.7°, p = 0.046) at 12 months. Conclusions: We recommend the PRWE score as a useful endpoint for further studies for this indication. To prove a 15% superiority over sham irradiation, we calculated that 750 patients need to be prospectively randomized.

Low Dose Radiation Therapy Induces Long-Lasting Reduction of Pain and Immune Modulations in the Peripheral Blood - Interim Analysis of the IMMO-LDRT01 Trial.

The treatment of chronic inflammatory and degenerative diseases by low dose radiation therapy (LDRT) is promising especially for patients who were refractory for classical therapies. LDRT aims to reduce pain of patients and to increase their mobility. Although LDRT has been applied since the late 19th century, the immunological mechanisms remain elusive. Within the prospective IMMO-LDRT01 trial (NCT02653079) the effects of LDRT on the peripheral blood immune status, as well as on pain and life quality of patients have been analyzed. Blood is taken before and after every serial irradiation with a single dose per fraction of 0.5Gy, as well as during follow-up appointments in order to determine a detailed longitudinal immune status by multicolor flow cytometry. Here, we report the results of an interim analysis of 125 patients, representing half the number of patients to be recruited. LDRT significantly improved patients' pain levels and induced distinct systemic immune modulations. While the total number of leukocytes remained unchanged in the peripheral blood, LDRT induced a slight reduction of eosinophils, basophils and plasmacytoid dendritic cells and an increase of B cells. Furthermore, activated immune cells were decreased following LDRT. Especially cells of the monocytic lineage correlated to LDRT-induced improvements of clinical symptoms, qualifying these immune cells as predictive biomarkers for the therapeutic success. We conclude that LDRT improves pain of the patients by inducing systemic immune modulations and that immune biomarkers could be defined for prediction by improved patient stratification in the future.

Low-dose radiotherapy for painful osteoarthritis of the elderly: A multicenter analysis of 970 patients with 1185 treated sites.

PURPOSE: Painful osteoarthritis is common in elderly patients, and low-dose radiotherapy has been demonstrated to provide effective symptomatic treatment. We examined the analgesic effects of low-dose radiotherapy for osteoarthritis in the elderly aiming to reveal potential differences in the response rates relating to increasing age. METHODS: A retrospective analysis was performed at two university hospitals including elderly patients (≥ 65 years) undergoing radiotherapy for osteoarthritis between 2008 and 2020. Pain intensity and response were quantified using the numerical rating scale (NRS) and the Pannewitz score. Age groups were defined for young old (65-74 years), older old (75-84 years), and oldest old patients (≥ 85 years). RESULTS: In all, 970 patients with 1185 treated sites and a median age of 76 years were analyzed. Mean NRS was 66 at baseline (t0), 53 after radiotherapy (t1), and 44 at first follow-up (t2) (p < 0.001 for t0-t1, t1-t2, and t0-t2). At t1, 1.5% exhibited a Pannewitz score of 0 (no pain), 58.5% of 1-2 (less pain), 36.1% of 3 (equal pain), and 3.9% of 4 (worse pain), while at t2, pain response shifted towards 6.9% (0), 58.6% (1-2), 28.1% (3), and 6.3% (4). Pain response did not differ between age groups at t1 (p = 0.172) or t2 (p = 0.684). In addition, pain response after re-irradiation (n = 384 sites) was 61.0% and was comparable between age groups (p = 0.535). CONCLUSION: Low-dose radiotherapy results in pain reduction in about two-thirds of treated sites with no difference relating to increasing age, showing that radiotherapy is an effective analgesic treatment for osteoarthritis even at advanced ages.

Low-dose radiation therapy for osteoarthritis and enthesopathies: a review of current data.

BACKGROUND: Osteoarthritis (OA), the most common degenerative joint disease, is associated with severe functional limitation and impairment of quality of life. Numerous reports have documented the clinical efficacy of low-dose radiotherapy (LD-RT) in the management of various inflammatory disorders, including OA. In this paper, we assessed the clinical literature involving the use of LD-RT in the treatment of OA, its dose-response features, possible underlying mechanistic features, and optimal therapeutic dose range. METHODS: We carried out a systematic review based on the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements and evaluated articles meeting the inclusion criteria for this review. RESULTS: A total of 361 articles were identified from databases, such as Scopus, PubMed, Embase, and Science Direct out of which 224 articles were duplicates and were discarded. Of the remaining 137 articles, 74 articles were un-related, 27 articles were review articles, eight were conference abstracts, three were letters, two were editorials, two were notes, and one was a book chapter. Finally, 20 articles met all the inclusion criteria and were included in this systematic review. DISCUSSION: Several single-arm retrospective/prospective studies showed advantages for LD-RT in the management of OA in terms of pain relief, improvement of mobility and function, and showed minimal side effects. Mechanistic considerations involve positive subcellular effects mediated by the activation of a nuclear factor erythroid 2-related transcription factor (Nrf2) mediated antioxidant response. Further research on both the short- and long-term effects of LD-RT on OA and other inflammatory disorders is recommended.

Anisotropy of the Radiation Field Following Canine Sn-117m Treatment.

ABSTRACT: Tin-117m (117mSn) is used to treated dogs with osteoarthritic joints by radiosynoviorthesis. The internal conversion and Auger electrons emitted by the 117mSn provide the therapeutic effect. Sn-117m also emits gamma rays, of which the most significant is 158.6 keV. The external radiation field around a treated dog is of interest to limit the dose to the owners/caretakers of the dog. The dog's torso attenuates the radiation being emitted toward the opposite side of the dog's body. This leads to a radiation field that is significantly non-isotropic. This study characterizes the anisotropy of this field to permit maximum dose rate measurements to be used to calculate the dose to individuals in the vicinity of the dog. Measurements were made in nine directions and at two distances, 0.3 and 1.0 m, to characterize common distances and spatial orientations for human-dog interactions. From these measurements, the percent reduction in the average dose rate compared to the maximum dose rate was determined. From a radiation safety perspective, the important factor is the minimum amount of shielding effectiveness or percent reduction that can be expected. A reasonable measure for this value is the fifth percentile of the shielding effectiveness distribution. The fifth percentile shielding effectiveness measures are 27% and 21% at 0.3 and 1.0 m, respectively.

Photobiomodulation Therapy Partially Restores Cartilage Integrity and Reduces Chronic Pain Behavior in a Rat Model of Osteoarthritis: Involvement of Spinal Glial Modulation.

OBJECTIVE: Chronic pain associated with osteoarthritis (OA) often leads to reduced function and engagement in activities of daily living. Current pharmacological treatments remain relatively ineffective. This study investigated the efficacy of photobiomodulation therapy (PBMT) on cartilage integrity and central pain biomarkers in adult male Wistar rats. DESIGN: We evaluated the cartilage degradation and spinal cord sensitization using the monoiodoacetate (MIA) model of OA following 2 weeks of delayed PBMT treatment (i.e., 15 days post-MIA). Multiple behavioral tests and knee joint histology were used to assess deficits related to OA. Immunohistochemistry was performed to assess chronic pain sensitization in spinal cord dorsal horn regions. Furthermore, we analyzed the principal components related to pain-like behavior and cartilage integrity. RESULTS: MIA induced chronic pain-like behavior with respective cartilage degradation. PBMT had no effects on overall locomotor activity, but positive effects on weight support (P = 0.001; effect size [ES] = 1.01) and mechanical allodynia (P = 0.032; ES = 0.51). Greater optical densitometry of PBMT-treated cartilage was evident in superficial layers (P = 0.020; ES = 1.34), likely reflecting the increase of proteoglycan and chondrocyte contents. In addition, PBMT effects were associated to decreased contribution of spinal glial cells to pain-like behavior (P = 0.001; ES = 0.38). CONCLUSION: PBMT during the chronic phase of MIA-induced OA promoted cartilage recovery and reduced the progression or maintenance of spinal cord sensitization. Our data suggest a potential role of PBMT in reducing cartilage degradation and long-term central sensitization associated with chronic OA.

Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients.

Osteoarthritis (OA) is the leading degenerative joint disease in the western world and leads, if left untreated, to a progressive deterioration of joint functionality, ultimately reducing quality of life. Recent data has shown, that especially OA of the ankle and foot are among the most frequently affected regions. Current research in OA points towards a complex involvement of various cell and tissue types, often accompanied by inflammation. Low-dose radiotherapy (LDRT) is widely used for the treatment of degenerative and inflammatory diseases. While the reported analgesic effects are well known, the underlying molecular mechanisms are only poorly understood. We therefore correlated a clinical approach, looking at pain reduction in 196 patients treated with LDRT with a pre-clinical approach, utilizing the K/BxN serum transfer mouse model using flow cytometry and multiplex ELISA for analysis. While an improvement of symptoms in the majority of patients was found, patients suffering from symptoms within the tarsi transversa show a significantly lower level of improvement. Further, a significant impact of therapy success was detected depending on whether only one or both feet were affected. Further, patients of younger age showed a significantly better outcome than older ones while needing fewer treatment series. When looking on a cellular level within the mouse model, a systemic alteration of immune cells namely a shift from CD8+ to CD4+ T cells and reduced numbers of DCs was observed. A general reduction of inflammatory cytokines was detected, with significant alterations in IL-4 and IL-17 levels, all of which could potentially be responsible for the highly effective clinical improvement in patients. Taken together our data indicate that LDRT can be regarded as a highly effective treatment option for patients suffering from OA of the foot and ankle, in terms of analgesic effects, especially in younger patients. Furthermore, the observed effects are mediated by an interplay of cellular and soluble immune factors, as observed in the K/BxN serum transfer model. With this interdisciplinary approach we aim to encourage the usage of LDRT as an additive treatment strategy not only as a last resort, but also earlier in the course of disease.