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15 Articles in Volume 21, Issue #4
Advanced Practice Matters: Needs Assessment in Pain Management Training
Analgesics of the Future: Novel Capsaicin Formulation CNTX-4975
Ask the PharmD: How to Improve Medication Adherence in Chronic Pain Management
Behavioral Medicine: Applying Mindfulness-Based Stress Reduction for Comorbid Pain and PTSD
Case Report: Multimodal Management of Osteoarthritis
Commentary: The PCP's Role in Preventing Chronic Back Pain
Guest Editorial: Structural Racism in Pain Practice and How to Combat the “Hidden Curriculum”
Hypermobile Ehlers-Danlos Syndrome: An Update on Therapeutic Approaches for Pain Management
Male Clinicians as Allies in Women’s Leadership: What Your Female Peers Want You to Know
Meet the Women Changing Pain Medicine
Perspective: It’s Time to Advocate for Early Interventional Pain Management
Research Insights: Is Spinal Fusion Surgery Being Overused in Back Pain Care?
Tips from the Field: Treating Pain in an Under-Resourced State
Utilizing Music Therapy to Manage Chronic Pain
Woman to Woman: Leaders Share Advice for the Next Generation of Pain Medicine Clinicians

Case Report: Multimodal Management of Osteoarthritis

With a focus on chronic knee pain stemming from osteoarthritis, the author weighs current and emerging treatment options, including analgesics and nonpharmacological therapies.

Osteoarthritis and Chronic Knee Pain: A Patient Case

A 62-year-old woman presents with a history of knee pain. She is overweight and has experienced progressive pain in the knees for the last several months. She describes her pain as a deep ache inside the knees and a grinding/sandpaper-like sensation with certain movements. Pain is localized, non-radiating and is intermittent. She has tried OTC acetaminophen and topical diclofenac with only transient and minimal relief.

Initial evaluation of this patient requires obtaining additional history to investigate other possible symptoms such as reports of signs of inflammation, joint instability, and neurological complaints. This should be followed by a focused physical exam which, at a minimum, should include visual inspection and palpation of the knees for changes in temperature and specific areas of tenderness, range of motion (ROM), presence of crepitus, a focused peripheral neurological exam (including reflexes, sensation, and motor testing), as well as brief evaluation of a more distal and proximal joint (ankle and hip respectively) in consideration of potential referred pain generators.

Focused examination reveals no apparent deformity or effusion, but slightly increased temperature to palpation with essentially normal ROM, no instability, and some fine crepitus.

There are no gross neurological deficits.

Plain films of both knees (including weight-bearing AP views) show moderate degenerative changes consisting of relatively symmetric lateral joint space narrowing along with some osteophytes, as seen in osteoarthritis (OA).

More than 27 million Americans are living with osteoarthrits and nearly half of them have moderate-to-severe disease. Osteoarthritis has a multifactorial etiology and genetic links. (Image: iStock)

Etiology of Osteoarthritis

More than 27 million Americans are living with OA and nearly half of them have moderate-to-severe OA. Osteoarthritis has a multifactorial etiology. Genetics play a significant role and it is seen more commonly in females and people over 55 years of age. Body weight affects joints mechanically due to excess forces, but there is also compelling medical evidence of a significant metabolic component with emphasis on the fact that there are important inflammatory factors in adipose tissue at play.

Adipose tissue is not an inert tissue (passive storage of energy) but rather, appears to be a real endocrine organ with the ability to induce chronic low-grade inflammation by the production and secretion of cytokines (eg, interleukin-1, tumor necrosis factor-a) and several inflammatory mediators (adipokines).

In some people, trauma plays a salient role (post-traumatic arthritis). This generally presents as markedly asymmetric arthritis affecting more severely a joint that has sustained prior significant trauma. Muscle weakness around the affected joints seems to play a role in its development but more so in its chronic negative symptoms – hence the importance of exercising.

Traditional OA theory emphasized it being a process solely affecting the articular cartilage by means of gradual aging and degeneration without a significant inflammatory component. However, we now know that OA is a disease of the whole joint and surrounding tissues, including bone, synovium, articular cartilage, and synovial fluid.  It involves inflammatory changes, ectopic bone formation and other underlying mechanisms. Age-related mechanisms that may be responsible for triggering OA symptoms and signs include oxidative stress, chronic inflammation/synovitis (increased production of pro-inflammatory cytokines), apoptosis (senescence of some cells in the joint and reduced capacity to regenerate), impaired proprioception, microtrauma due to ligamentous laxity, and sarcopenia.

Sarcopenia contributes to joint instability as muscles provide extrinsic stability to the joints: stronger and balanced muscles help to protect joints from excessive forces around them by absorbing and transferring forces about them. Management options for OA include a variety of nonpharmacological and pharmacological options. Some of these options are listed in Table I.


Weighing Treatment Options for Osteoarthritis 

NSAIDs and Supplements

Non-steroidal anti-inflammatory drugs (NSAIDs) are still considered the standard of care for OA. However, adverse drug reactions may limit their use, particularly in the elderly. Adverse drug reactions include dyspepsia, GI ulceration/bleeding, renal dysfunction, platelet disorders, risk in coronary artery disease, exacerbation of congestive heart failure and hypertension, hepatic toxicity, and skin and CNS toxicity.

Topical forms have a more favorable safety profile and should generally be considered as first-line agents. These include some NSAIDs and multiple rubefacients, including methyl salicylate, menthol, camphor, and others. Other topical options include capsaicin and topical local anesthetics. These agents should be considered and tried as first-line agents in OA due to their relative safety and underestimated efficacy.

Nutritional supplements, specifically glucosamine and chondroitin sulfate, are also commonly used. These are constituents of cartilage matrix, but their mechanism of action is unknown.  They are generally considered safe, tend to be well-tolerated, and have some good clinical results.

Physical Therapy, Braces, and Assistive Devices

Physical therapy management of OA involves aerobic conditioning and muscle strengthening.  Strengthening promotes better force distribution, effectively unloading joint tissues (mainly bone and cartilage) in favor of muscle. Range of motion exercises can be performed on a stationary bicycle for knee and hip with low to no resistance if necessary. Even in the face of an acute flare, isometric exercises are always safe and well-tolerated.

Guidelines published in 2020 by the American College of Rheumatology strongly recommend exercise for OA affecting the knee, hip, and hand. Weight loss is also strongly recommended for individuals with osteoarthritis of the knee and hip.

Aquatic therapy is a great option for individuals whose symptoms are severe enough to limit their ability to perform land-based exercises. It reduces gravitational load, provides compression, induces analgesia, and relaxes stiff muscles while promoting aerobic fitness.

Physical therapy modalities (heat, cold, electrical stimulation) may be used in the initial stages of a program to provide some analgesia.

Braces and assistive devices can help to mechanically unload the joint and provide stability in cases of ligamentous laxity or insufficiency. Simple neoprene sleeves are well-tolerated, provide some warmth (reported by some patients as analgesic and relaxing), and are believed to improve proprioceptive input from the affected area. More rigid/sturdy braces can be used to  compensate for ligamentous laxity and joint instability. Canes and walkers help to unload the joints and widen the base of support. These have specific indications and contraindications.

Devices should be properly adjusted to the individual with training on their use by a knowledgeable therapist.


Steroid injections can prove helpful in acute flares. However, their efficacy and safety have been called into question. They are generally considered safe for repeated use in a degenerated joint with a maximum frequency of every 3 to 6 months. A recent study comparing structured physical therapy (PT) with corticosteroid injections (CSI) for knee OA showed that the PT group had less pain and functional disability than the CSI group at 1 year.1

Viscosupplementation involves injection of various formulations of hyaluronic acid (HA) into the arthritic joint. In OA, the molecular mass of HA reaches approximately 40% of normal, rendering it less viscous and affecting its ability to protect and lubricate the joint. Intra-articular viscosupplementation seeks to replace the “diseased” synovial fluid with a more normal counterpart, helping to relieve inflammation and providing improved viscosity and shock absorption. These agents are only approved for use in the knee in the US but are widely used and approved for use in other synovial joints elsewhere in the world. Their efficacy can be quite variable with mixed levels of evidence in the medical literature.


Genicular nerve neurotomy in the form of cool radiofrequency ablation (cRFA) of the branches of the genicular nerve that provide sensory innervation to the knee structures has been shown to effectively dull the pain associated with OA. This is similar to the longstanding concept of medial branch neurotomy for spinal zygapophyseal-generated pain. A study published last year comparing a single HA injection and cRFA showed longer-lasting and more pain relief in patients undergoing cRFA.2 This tends to be a great option when intra-articular injections are ineffective or contraindicated.

Regenerative Therapies

A wide range of regenerative therapies have become available for the management of musculoskeletal disorders, including OA. Many of these are referred to as orthobiologics, biological alternatives to address underlying inflammation through stimulation of growth factors, suppression of inflammatory cytokines, and promoting tissue regeneration. These include platelet-rich plasma (PRP), amniotic fluid/membrane tissue, and stem cells, including adipose tissue preparations and bone marrow aspirate/concentrate. (See a recent case report on adipose prolotherapy for knee OA).

ver the past few years these injectables have become nearly ubiquitous. However, consistent and solid evidence for their effectiveness is still lacking. These products tend to be quite variable depending on intrinsic individual subject variability as well as different harvesting, processing, and administration methods. For instance, in the case of PRP, things such as the spin time and method, separation technique, injectate volume, frequency of injections, needle gauge (for harvesting and injection), and quality of injectate (platelet concentration, leukocyte rich vs poor) to name a few, have not been standardized, rendering pooling of outcomes data from different studies generally invalid. Additionally, evidence for tissue repair or regeneration is inconclusive and these therapies tend to be quite expensive.3,4

An older and very affordable form of regenerative injectable therapy is proliferant therapy (prolotherapy), where an irritant (mainly hypertonic saline, glycerin, or dextrose in high concentration) is injected around the damaged tissues to trigger an inflammatory reaction that is theorized to lead to tissue repair. These techniques are widely used in the management of soft tissue injuries with some variable evidence supporting their efficacy.


Surgical management should be reserved for patients who continue having significant functional impairments despite conservative management attempts in the presence of anatomical pathology that is concordant with the patient’s complaints and physical exam findings.

Emerging Analgesics for Osteoarthritis: Monoclonal Antibodies

A novel approach to the management of osteoarthritic pain involves modulating pain perception by blocking the effects of nerve growth factor (NGF), a neurotrophic factor discovered in 1950 for its properties of promoting growth and survival of peripheral sensory and sympathetic nerve cells in mammals.Nerve growth factor levels are elevated in several human pain conditions, and increased NGF levels have been associated with increased perception of pain in animal models of injury or inflammation. Blocking NGF has been shown to improve symptoms of pain and hyperalgesia in animals.

As a result, novel analgesic drugs that block NGF are being developed. Tanezumab is a humanized IgG2 monoclonal antibody that binds and blocks NGF receptors with high affinity and specificity.It has been shown effective in clinical trials, but concerns about side effects held its release. Others in development are fulranumab and fasinumab. Initial clinical trials with Tanezumab (administered by subcutaneous injection) in knee and hip OA showed promising results. However, safety concerns led to a temporary moratorium on clinical trials with NGF-binding antibodies due to the development of osteonecrosis and rapidly progressive OA (RPOA) in patients during clinical testing. After the moratorium was lifted, clinical trials with NGF-binding antibodies proceeded but safety concerns linger resulting in the FDA halting their approval. The safety concerns and risks from previous investigations should definitely be taken seriously.5,6

A Word About Opioids in Osteoarthritis Management

Opioids should be avoided as there is no medical evidence for their efficacy on a long-term basis. In fact, recent studies have shown that opioid use prior to joint replacement and other major orthopedic surgery procedures leads to worse surgical outcomes, suggesting that clinicians should consider limiting the use of opioids prior to such procedures.7 A systematic review and meta-analysis of 18 RCTs including over 9,000 subjects with hip and knee OA demonstrated that opioids provided minimal relief of OA symptoms at each time point and even less improvement in function. Stronger opioids demonstrated consistently inferior efficacy and overall worse safety compared to weak/intermediate opioids.8

Case Recommendations for Treating Osteoarthritis

Returning to the presented patient case, initial pain control can be addressed with physical therapy (PT) modalities and NSAIDs. Rubefacients and glucosamine/chondroitin can also be considered. The patient should engage in an active exercise program. These exercises should focus on thigh musculature strengthening and stretching of any tightness of the soft tissues. A maintenance exercise program should be prescribed for her to continue performing on a long-term basis and she should engage in a consistent aerobic exercise routine.

If pain interferes with progress in PT, interventional procedures (such as steroid injections, viscosupplementation, and others described above) could be used. If this patient were a brittle diabetic, a specific extended-release injectable triamcinolone acetonide suspension (Zilretta) could be considered as it has been demonstrated to be safe with negligible alterations of systemic glycemia.

Unfortunately, lifestyle modification approaches (exercises and lifestyle counseling) are still highly underutilized.9 Results of the Arthritis, Diet, and Activity Promotion Trial (ADAPT study) published over 15 years ago showed that weight loss positively affects pain outcomes.10

Out of all the available behavioral interventions, research most strongly supports the combination of diet and exercise-based intervention in improving pain outcomes. In this study of a cohort of overweight adults over age 60, the diet and exercise group (vs diet only or exercise only) had significant improvement in physical functioning, self-reported pain, mobility, and weight. Some individuals experience OA as a chronic rather than a progressive disease.  For instance, researchers in France recently identified 4 distinct trajectories of knee and hip OA patients over 5 years in terms of significant pain and functional limitations: severe, moderate, low, and none.11 They highly recommend management of weight, fatigue, physical activity, and psychosocial distress concurrently to achieve better outcomes, particularly for patients with severe and moderate pain and functional limitations.

Education about the condition, its potential deleterious effects on overall health and function and how to mitigate these through lifestyle modifications and judicious stepwise use of multiple pharmacological, interventional and ultimately surgical options is the key to help your patients.


The opinions expressed here are those of the author and not those of the US Department of Veterans Affairs or his employers.


Last updated on: July 8, 2021
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