OA

Goal of the Study?

In this research review article from the Annals of Medicine and Surgery 1 the authors’ purpose was to focus on the update of clinical prospects and management of osteoarthritis as well as future treatment possibilities.

 

Why are they doing this study? 

Osteoarthritis is a general term that incorporates several different joint diseases.  OA’s main effects include cartilage degradation, acute and chronic synovial inflammation, subchondral bone alteration, the presence of osteophytes and changes in synovial fluid.  The first studies on OA were conducted about 130 years ago and OA is now recognized as a multifactorial complex disorder.  OA was once believed to be a degenerative condition, but it is now known to have an infectious cause as well as a metabolic etiology.  The exact pathophysiology of OA remains unclear and both the pharmacological and non-pharmacological management of OA is continually evolving.

 

 

What was done?

The review began with an overview of OA’s inflammatory pathology focusing on the various cytokines, a group of secreted polypeptides that appears essential for the initiation of inflammation. Some cytokines are released in response to acute chronic inflammation and have anti-inflammatory properties and responses.   The majority of the review covered the pharmacological and non-pharmacological management of OA.  The more effective treatments include:

  • Exercise which is the recommended first-line treatment of OA.
  • Heat and Cold Therapy.  Heating decreases discomfort and increases the expression of Heat Shock Protein 70 which has both a relaxing effect and is involved in cartilage defence, reducing inflammation and preventing chondrocyte apoptosis.  The only reported benefit of cold therapy seems to be pain reduction.
  • Transcutaneous Electrical Nerve Stimulation (TENS), Low-level Laser Therapy, Massage, Acupuncture and Assistive Devices (canes, braces and insoles) can also improve mobility but seem to be more effective if used in conjunction with exercise.

The effectiveness of various pharmacological management tools were also discussed.  These included NSAIDs and other analgesics, topical agents, intra-articular therapy, Hyaluronic Acid, Anti-cytokine Therapy, Omega 3 fatty acids and Herbs and Ayurvedic formulations.  It appears that some ancient herbal Ayurvedic formulations, such as Triphala, Triphaghula, Balaraja and Dashamoola extracts, are re-emerging as an effective treatment option without the side effects of potentially risky medications.  Arthroscopic and replacement surgery are also discussed and use cases are provided. 

 

What did they find?

The researchers found a few gaps in the current pathogenesis of OA.  They also discussed some promising recent developments, especially ones that target the articular cartilage molecular process.  OA seems to present itself with overlapping endotypes and as such a single-targeted approach is not likely to be as successful as an integrated personalized approach.

 

Why do these findings matter?

Osteoarthritis (OA) severely restricts the everyday activities of senior citizens.  As the population ages, the frequency and prevalence of OA is expected to double over the next decade.  By age of 65, most people have radiographic proof of OA and by age 75 this increases to about 80% of the population.  OA is currently the most prevalent articular disease worldwide. Even though the exact pathophysiology of OA is unclear, there appear to be some effective non-pharmacological interventions.

 

At Dynamic Disc Designs, we work to help professionals explain the anatomy (in a dynamic and postural way) to help patients understand the positive things they can do for themselves to help reduce their pain.

LSS

Goal of the Study?

In this exploratory cross-sectional study pre-proof article (prior to publication) to be published in the Journal of Osteoarthritis and Cartilage 1 the authors’ goals were twofold:

  • Report on the proportion of patients in a Danish OsteoArthritis (OA) primary care program that had knee OA, hip OA and persistent Lower Back Pain (LBP).
  • Identify what proportion of these 3 categories also had symptoms associated with Lumbar Spinal Stenosis (LSS)

 

Why are they doing this study?

Musculoskeletal comorbidities are common in people with back pain and OsteoArthritis (OA) and associated with increased disability.  Musculoskeletal comorbidities are also present in people with Lumbar Spinal Stenosis (LSS), a disabling low back condition primarily affecting older people.  Evidence suggests that LSS and knee and hip OA often occur.  In one Canadian study, 77% of patients undergoing surgical decompression for LSS reported knee and hip OA.  In a US study, clinically defined knee and hip OA was reported in 32% and 17% of LSS patients.  However, it is not known if symptoms associated with LSS are common in people with knee and hip OA in primary care programs.

What was done?

A total of 11,125 people with a primary complaint of persistent lower back pain and/or knee or hip OA from a registered in a Danish group-based education and exercise program called Good Life with osteoArthritis in Denmark (GLA:D®), were given a questionnaire to identify the symptoms of LSS.  Two sets of clinical criteria were used to build the self-reporting questionnaire; Tomkins-Lane Criteria and the Genevay Criteria. Both these LSS classification tools use clustering of symptoms of leg and buttock pain during a series of activities to define the level of LSS.

 

What did they find?

Despite the high prevalence of LSS symptoms in the 10,234 GLA:D patients surveyed, less than 10% were considered to have LSS by either the Tomkins-Lane or Geneway classification criteria.  When looking at the individual symptoms the prevalence of self-reported LSS symptoms varied greatly between the three cohorts; Knee OA, Hip OA and persistent LBP.  LSS symptoms of transient pain or numbness associated with the lower extremity items were found in 71% of patients with persistent LBP versus 50% for hip OA and 40% for knee OA.  This pattern was observed for all LSS symptoms except for numbness in the soles of both feet.  Only 10-11% of all three cohorts had this LSS symptom. 

 

Why do these findings matter?

Self-reported LSS symptoms are commonly reported by people treated in primary care for hip or knee OA, although not as frequently as those with persistent LBP. Despite symptoms of LSS being common, only a small percentage actually meet the Tomkins-Lane and/or Geneway clinical LSS threshold. 

 

At Dynamic Disc Designs we understand that topics related to osteoarthritis and stenosis are common in a clinical setting. Providing professionals with realistic modeling can be a time saver when these types of conversations comes up. We hope to help you build a solid, trustworthy, relationship with the patients you care for in a credible and evidence-based way.

Neurobiology

Goal of the review?

In this review 1, the authors focus on recent advances in understanding the nociceptive and neuropathic components of pain, as well as treatments for skeletal pain. 

 

Why are they doing this review?

Skeletal pain neurobiology is widely prevalent and has a significant impact on an individual’s quality of life and the broader society, as it is a leading cause of work disability. For this reason, the authors argue that understanding the mechanism that drives skeletal pain is critical to the prevent and treat pain.

 

What did they find?

Primary afferent sensory nerve fibres that innervate the skeleton

Unlike the skin innervated by various sensory nerve fibres, including A-beta, A-delta, C-fibers and others, the adult skeleton (bone and joint) is predominantly innervated TfkA+ sensory nerve fibres and CGRP.

While the same nociceptive nerve fibres innervate bone and joint, the density, pattern, and morphology are very different. For example, the periosteum (tissue enveloping the bones) has the largest sensory nerve fibres with A-delta and C-sensory nerve fibres that detect injury or alteration. In contrast, the articular cartilage of the knee and temporomandibular joint lack any innervation by sensory nerve fibres or vascularization by blood vessels. Therefore, it is believed that pain from a joint injury must come from the ligaments, synovium, and muscle.

Skeletal pain is also driven by the innervation of adrenergic and cholinergic sympathetic nerve fibres. Research has shown that these regulate bone destruction, bone formation and more, and therefore may play a significant role in disease progression in cartilage, bone, and skeletal pain.

Additionally, studies have shown that following injury to the skeleton, there is an interaction between sensory and sympathetic nerve fibres that may play a role in OA and complex regional pain syndrome. 

 

Nociceptive and neuropathic components of skeletal pain

Bone fractures and injury to articular cartilage are characterized by sharp stabbing pain and a lesser dull aching pain. Following injury, A-delta and C-fibers in the synovium and subchondral bone are sensitized. Normally non-noxious loading and movement of the joint are perceived as noxious stimuli. However, as articular cartilage lacks innervation, the location of the nerves driving pain is not known. Moreover, there is no clear correlation between the extent of joint destruction and the frequency and severity of joint pain. 

Research suggests there may be a neuropathic component in different types of skeletal pain. For example, in some types of cancer pain, the tumour cells destroy the distal ends of sensory nerve fibres that innervate the skeleton, which is then accompanied by an increase in movement-based pain. Another mechanism of neurobiology pain may arise from the sprouting of sensory and sympathetic nerve fibres. In mouse models of bone cancer, the number of nerve fibres per unit increased exponentially in a way not normally seen in bone.  

 

Neurochemical and structural changes to the Central Nervous System (CNS)

Little is known about the mechanisms that drive central sensitization in skeletal pain. However, it is thought to result when chemical, electrophysiological, and pharmacological systems that transmit and modulate pain are changed in the spinal cord and higher brain centers. 

 

Potential treatments for skeletal pain

The authors point out that while analgesics are needed to control pain better, an important therapeutic approach could induce bone or cartilage formation following injury. There are currently two classes of drugs to treat age-related bone loss: antiresorptive and osteoanabolic. However, both classes of drugs have limitations. 

Recent findings have outlined several new therapeutic targets for treating bone loss. Two of these inhibitory proteins that show promise are: sclerostin and Dickkopf-1. A Phase 1 study demonstrated that a dose of anti-sclerostin antibody increased bone density in the hip and spine in healthy men and postmenopausal women.

One question the researchers raise is how much neurobiology pain should be relieved. While it is beneficial for cancer patients to have their pain eliminated, the same is not true for patients with skeletal pain due to OA, bone fracture or ageing. The elimination of all pain could lead to overuse and more deterioration. Therefore, finding a treatment that could block pain while at the same time promoting bone formation and healing is critical. 

 

Why do these findings matter?

Understanding the causes of skeletal pain will help lead to more effective and targeted treatments. 

Pain Syndromes

Goal of the Study?

In this study, 1, the authors have developed a framework to differentiate Parkinson’s Disease (PD) pain from non-PD-related pain and classify PD-related pain into 3 groups based on already validated mechanistic pain descriptors – nociceptive, neuropathic and nociplastic. 

 

Why are they doing this study?

In Parkinson’s disease (PD), about 20% of patients experience chronic pain at diagnosis. This number climbs to 80% during the course of the disease. PD pain has been divided into three categories: de novo pain related to disease onset and symptoms (PD-related); previous chronic pain aggravated by the disease or treatment (PD-indirectly-related); pain that is neither caused nor aggravated by the disease (PD-unrelated). Moreover, pain is considered PD-related when one of the following applies: when occurring along with the first motor symptoms, when occurring/aggravated during the OFF stage of the disease, when occurring at the same time with choreatic dyskinesia or when improved by dopamine treatment. However, these categories have not been validated or tested, making diagnosing and treating pain in PD. In response to this need, the authors develop a classification system to define and distinguish PD-related pain from non-PD-related pain.

 

What was done?

The authors used an international, cross-sectional, multicenter study. They recruited 159 non-demented PD patients and 37 healthy controls across 4 centers. Using the mechanistic pain descriptors (nociceptive, neuropathic and nociplastic), the authors developed a PD pain classification system (PD-PCS) by including classic pain-related situations of PD into each category. The severity of PD-related pain syndromes was scored by ratings of intensity, frequency and interference with daily living activities. Finally, they did an analysis and validation of their scale.

 

What did they find?

This study provides a unifying system for pain in PD that differentiates between PD and non-PD pain and outlines a treatment-based and mechanistic classification system for PD-related pain. Using this system, the authors found that 77% of patients experienced PD-related pain, with 15% suffering more than one syndrome at the same time. PD-related pain with nociceptive, neuropathic or nociplastic components was diagnosed in 55%, 16% and 22% of participants, respectively. Mixed pain syndromes were mostly found in nociceptive pain combined with nociplastic (12.7%) or neuropathic (9.6%). Pain unrelated to PD was found in 22% of participants, versus only 5% of controls. 

Concerning the PD-PCS, the authors found that pain severity scores significantly correlated with commonly used questionnaires such as the pains’ Brief pain Inventory and McGill Pain questionnaire. They did not find that the PD-PCS scores correlated with a motor score.

Finally, they suggest that the three pain types identified by the PD-PCS are different pain syndromes and reflect different mechanistic backgrounds and, potentially, different treatment approaches.  For example, they found that patients with higher nociceptive pain scores had worse quality of life scores, but this was not found for patients with nociplastic pain. 

 

Why do these findings matter?

Better classification of pain in PD will ensure that PD patients’ pain is treated more effectively and timely, ultimately contributing to better outcomes.

 

spinal mobility

Goal of the Study?

The goal of this study [1.Spinal mobility in radiographic axial spondyloarthritis: criterion concurrent validity of classic and novel measurements] is to evaluate spine range of motion (ROM) measured by tri-axial accelerometers compared to both current clinical tests and radiography in radiographic Axial spondyloarthritis (AxSpA) patients. 

 

Why are they doing this study?

AxSpa is a chronic and progressive form of inflammatory arthritis. To measure progression and plan treatment, there is a need to measure indicators for spinal mobility in forward and lateral bending. Currently, this is often done using a clinical tape measure. However, research has illustrated that there is poor validity using a tape measure to assess spine mobility compared to the images and RoM from radiographs. However, with the risks associated with repeated exposure to radiation for radiographs, and the lack of validity in using clinical tape measures, there is a need for better alternatives. To that end, research has illustrated the value of devices that incorporate strain gauges and/or accelerometers to measure spinal curvature.

spinal mobility

A novel measuring approach to minimize radiation exposure.

 

What was done?

This study recruited fifteen radiographic Spondyloarthritis patients. First, each participant had lateral and posterior-anterior radiographs taken standing upright. Following this, each participant completed three RoM trials in forward flexion, right lateral and left lateral bending. In total, five lumbar radiographs were taken. For each participant, three measurements were collected: tape, synchronized radiograph and accelerometer measurements at the end range of forward and bilateral lateral flexion. The researchers then used statistical software to determine reliability.

 

What did they find?

The findings of this research support using accelerometers as a replacement for sagittal spine mobility, but not lateral. The accelerometer measure of the sagittal spine had a stronger correlation to the radiographic measure than all tape measures. They argue that this approach can overcome some of the inherent challenges with tape, such as skin stretching. In lateral bending, the Lateral Spinal Flexion tape (LSFT) correlated stronger than the accelerometer method. Furthermore, an accelerometer-derived measure of frontal plane spine mobility underestimated lateral bend angles from the radiographs. It demonstrated a moderate correlation to the radiographic gold standard lower than either the LSFT or DT.

 

Why do these findings matter?

The use of accelerometers can limit patients’ exposure to ionizing radiation through repeated radiographs in the AxSpA population. Improved ability to measure spinal changes is important to evaluating and managing disease progression and treatment. 

 

degenerative joint disease

Goal of the Study?

In this study 1, the authors investigate degenerative joint disease in the spine and major peripheral joints (shoulder, elbow, hip and knee) in chimpanzees, lowland gorillas and bonobos.

 

Why are they doing this study?

Degenerative joint disease is one of the most common pathological musculoskeletal conditions in human populations. It has also been observed in a variety of nonhuman animals, including nonhuman primates. Existing research has illustrated degenerative disease in chimpanzees, gorillas, orangutans, gibbons, macaques, baboons and probosci’s monkeys. Overall, prevalence has been reported as quite low in wild monkeys (with some exceptions) compared to colony-reared Old-World monkeys. 

The authors want better to understand the evolutionary basis of degenerative joint disease. 

 

What was done?

This investigation’s skeletal materials are drawn from two samples of chimpanzees, a sample of lowland gorillas and a small sample of bonobos. The samples from the chimpanzees are from Gombe National Park, Tanzania, while the other materials are from museum materials originally collected in west/central Africa. In total, 5807 sample surfaces for vertebral osteophytosis (VOP), 12,479 surfaces for spinal osteoarthritis (OA) and 1211 joints for evaluation of peripheral joint OA.

The human osteological samples are from two areas, Central California and a group of Inuit from Alaska.

The presence of VOP was based on a determination of osteophyte development. OA presence was based on hypertrophic development and changes to joint spacing. The severity of VOP and OA was scored based on slight, moderate or severe.

 

What did they find?

All apes display significantly less spinal disease compared to humans. The authors suggest that this is most likely related to movement on two legs. Among the African apes, gorillas are slightly more involved in the spine than chimpanzees with almost no spinal degeneration. Both bonobos and gorillas have significantly more involvement than chimpanzees in the cervical and thoracic regions (but the sample size for bonobos is so small that it is hard to say there is any significance).  As with previous research, the authors found that colony reared Old World monkeys, such as macaques, have higher OA levels than other free-ranging apes. The authors argue that the variation between humans and African apes in VOP and OA prevalence may be explained by human longevity.

 

Why do these findings matter?

This study can help understand basic processes in degenerative joint disease among humans and our closest relatives in a broader evolutionary context. 

 

Innervation

Goal of the Study?

In this study 1, the authors use a rat model to examine the time-course development of pathological joint changes and correlate them with pain-related behaviour in OA. 

Why are they doing this study?

There is a very high incidence of Osteoarthritis (OA) in the elderly population, and it is a leading cause of disability and pain. However, there is a lack of knowledge of OA’s pain mechanisms, particularly the role that neuropathic pain (NP) plays in OA.

OA has been described as a degenerative rather than an inflammatory disease. However, in recent years research has identified the many inflammatory processes that take place in OA.  Existing OA models have shown how this inflammation is supported by overexpression of nerve growth factors causing nociceptive fibres to grow into inflamed joints. This inflammatory process helps explain why there is a poor correlation between radiographic changes and pain levels in OA patients. Moreover, some patients continue to experience pain after a total joint replacement, suggesting that OA can result in neuropathic pain (NP). 

What was done?

The researchers used a rat monoiodoacetate (MIA) model of the ankle joint. MIA results in pathological changes and pain-like behaviour common with those observed in human OA. This model has been used extensively in research and is well validated.

They injected MIA or saline into a total of 126 male rats. For this study, they used the rat ankle joint as it receives most of its nerve supply from the sciatic nerve, which is used most commonly in NP models. From this, they assessed a variety of changes, including pain-related behaviour, hypersensitivity, reaction to cold and heat, changes to normal movement, cartilage degeneration, bone degeneration, and the effects of drug treatments.

What did they find?

 Overall, the study provided a time-course view of the development of pathological changes to the joint and the associated pain-related behaviours. 

The researchers found significant innervation increases at specific periods of time that coincided with mechanical hypersensitivity at 4 weeks and pain in response to cold at 5 weeks. X-ray findings showed significant cartilage and bone degeneration and joint space narrowing at 5 and 10 weeks. 

The study also illustrated changes in sensory and sympathetic innervation of joints in the subchondral bone and synovial membrane at 5 and 10 weeks.  This increased concentration of sensory and sympathetic fibres was associated with pain-related behaviour and similar to those observed in NP models. Furthermore, they found that pain-related behaviour and extensive joint damage were associated with the expression of activating transcription factor 3 (ATF3) in the dorsal root ganglia (DRG), as well as the microglia and astrocyte changes in the dorsal horn. Using various pharmacological treatments to inhibit or block sympathetic fibres and glial could suppress pain-related behaviour. They argue that these findings suggest that multiple factors contribute to OA pain, including inflammatory changes in the joints, supporting the theory of a neuropathic component in OA.

Why do these findings matter?

As pain is the main reason patients seek medical help, effective pain management is critical to improving life quality. Therefore, understanding what causes pain will help in the development of pain management protocols and treatments.