Joint Injections for Acute Pain

Chikezie N. Okeagu

Alex D. Pham

Scott A. Scharfenstein

Alan David Kaye

Introduction

Joints, the junctions between two or more bones in the body, are frequent sources of pain. Pain can emanate from the joint itself, termed arthralgia, or from adjacent tissues, such as muscles and tendons. Joint pain can be acute or chronic and arise from a vast array of causes, including inflammation, infection, crystal deposition, cartilage degeneration, and trauma. Regardless, the initial approach to a patient with joint pain involves developing a differential diagnosis to help identify the underlying pathophysiological process. A thorough history and physical examination in conjunction with judiciously acquired laboratory tests are imperative. Details such as the number of joints affected, the type of joint (ie, axial skeleton vs peripheral joints), the chronicity of pain, and associated symptoms can help indicate a diagnosis and guide treatment. Pain that occurs as a result of a systemic disease, such as gout or rheumatoid arthritis (RA), necessitates treatment targeted at the underlying cause. Likewise, infection-induced joint pain requires eradication of the culpable pathogen. Commonly, joint pain is found to be the result of degeneration, overuse, or acute injury. In these situations, a variety of treatment options are available. In these instances, first-line interventions include activity modification, physical therapy, and analgesics, such as acetaminophen and nonsteroidal anti-inflammatory drugs. If these treatments are inadequate, more invasive measures can be considered. One such modality, intra-articular injection, involves directly introducing medication or other substances into the joint to modulate the local environment in hopes of alleviating symptoms. Intra-articular injections are used broadly across numerous joints in the body, including those in the extremities, foot/ankle, hands, and spine. While most commonly used in the management of chronic pain conditions, such as osteoarthritis (OA) that have been refractory to other treatments, intra-articular injections are also often helpful when used as adjuncts in the treatment of acute exacerbations of chronic conditions, such as OA, gout, or RA, and to help alleviate acute pain caused by injury or surgery. This chapter will present an overview of the various agents that are available for use in intra-articular injection and their utility in the treatment of a variety of acute pain conditions.

Intra-articular Injection Agents

Corticosteroids

Corticosteroid injections are a commonly utilized method of treating painful musculoskeletal conditions such as OA and RA of the knee, hand, shoulder, hip, and other joints. Corticosteroids are a group of synthetic analogs of the natural steroid hormones produced and released by the adrenal cortex, glucocorticoids and mineralocorticoids. These hormones regulate a variety of physiological processes in our bodies, playing roles in homeostasis, metabolism,
and cognition. They also have significant anti-inflammatory and immunomodulatory effects. Corticosteroids are important in the treatment of allergic and inflammatory disorders to suppress undesirable actions of the immune system.¹ The mechanism of action by which corticosteroids produce their effects is complex. The classic mechanism that leads to most of the anti-inflammatory and immunosuppressive effects are mediated through the glucocorticoid receptor in the nucleus of cells where gene transcription is altered, causing inhibition of gene expression and translation of inflammatory end products. This leads to a reduction in proinflammatory mediators involved in the inflammatory response, such as phospholipase A2, cyclooxygenase-2, macrophages, eosinophils, lymphocytes, mast cells, and other inflammatory mediators.²

Types of corticosteroids used

There are five main types of corticosteroids FDA approved for intra-articular injections: methylprednisolone acetate, triamcinolone acetonide, dexamethasone, betamethasone sodium phosphate, and betamethasone acetate.³ Corticosteroids are classified as soluble or insoluble in water. The acetate/acetonide formulations are insoluble because of their hydrophobic steroid ester groups. Insoluble steroids require hydrolysis by cellular esterases to convert to their active forms, so these theoretically have a longer duration of action at the site of injection. Sodium phosphate formulations are soluble in water and do not require conversion to an active form; thus, onset of action is rapid. Soluble preparations also have a potency five times greater than ester formulations, requiring a much smaller dose to achieve similar effects. Ester compounds also contain larger size particles and tend to coalesce and form larger aggregate “crystals.” Nonester compounds are freely soluble in water and do not aggregate.⁴ Water-soluble formulations can also diffuse rapidly from the injected joints and tend to exert more systemic effects than their counterparts. Therefore, the duration of effect is inversely related to the solubility of the preparation.⁵ According to multiple trials, there is no difference in efficacy of using any of the above corticosteroids for intra-articular injections, as long as each are being used for the correct indication, dosing, and timing.¹

Side effects and contraindications

Side effects to corticosteroids are numerous and are usually related to dosage, duration of administration, added contaminants, and particulate size. Chronic administration of corticosteroids, even at low doses, has been shown to cause adverse physiologic effects, the most significant being suppression of the HPA axis (hypothalamic-pituitary-adrenal). Other long-term sequelae include osteoporosis, immunosuppression, growth suppression, acne, skin atrophy, cataracts, decreased wound healing, and weight gain. Short-term therapy with corticosteroids is associated with adverse effects but is usually not associated with longterm complications. Some short-term effects include hyperglycemia, hypertension, poor wound healing, edema, psychiatric sequelae, and electrolyte disturbances. Intra-articular joint injections are a great way to provide prolonged concentrations of the steroid in the synovial fluid and synovium while limiting high plasma concentrations thereby avoiding systemic effects.²

In general, corticosteroid joint injections are relatively safe, but contraindications do exist. The main concern with injecting into a joint is the introduction of bacteria into that joint, potentially leading to septic arthritis. Staphylococcus aureus is the most common organism involved, with other organisms like coagulase-negative staphylococci and anaerobes present occasionally.⁶ Local cellulitis, active septic arthritis, acute fracture, bacteremia, and joint prosthesis are absolute contraindications. Some relative contraindications include minimal relief after two previous injections, bleeding risk due to a coagulopathy or a patient on blood thinners, osteoporosis of surrounding joint, and uncontrolled diabetes. If a patient is on blood thinners, clearance from cardiology should be obtained prior to stopping or bridging anticoagulants.⁵

Indications

The anti-inflammatory effects of intra-articular corticosteroids have been well established in the treatment of inflammatory disorders. OA is the most common indications for intra-articular steroid injections, especially in large weight-bearing joints with bone on bone pain, such as the knees and hips. RA, especially with persistent activity in large or medium-sized joints can slow joint erosion. Other inflammatory conditions indicated include reactive arthritis, gout, psoriatic arthritis, and other spondyloarthropathies.⁵

Effectiveness

The clinical effectiveness of intra-articular corticosteroid injections is highly debatable, and many studies showed limited if any long-term improvements in pain and functionality. A review by Cato looked at multiple studies conducted on the effectiveness of osteoarthritic knee steroid injections and concluded that intra-articular steroid injections of the knee do show statistically significant results. However, pain relief was only statistically significant within the first 2 weeks. There was only small benefit at 8 weeks and little or no benefit at 12-26 weeks.⁷ Other studies have shown better results for other disease processes such as synovitis in patients with RA.⁸ Overall, intra-articular steroids likely do have a significant clinical effect despite the various results by a multitude of studies. However, many factors likely contribute to clinical effectiveness, such as type of steroid used, dosage, psychosocial components, and technique. Also, patients with greater pain, presence of effusion, and less structural damage are more likely to benefit from intra-articular steroids.⁷

Frequent use of intra-articular steroid injections is usually not recommended against. One randomized trial studying patients with symptomatic knee OA injected their subjects every 12 weeks for 2 years and found that there was a minimal statistically significant difference in decreasing their pain. Long-term therapy has also been linked to intra-articular structural damage. This study also found significantly greater cartilage volume loss in patient knee joints.⁹

Hyaluronic Acid

Hyaluronic acid is a compound that can be considered for injection in the management of joint pain. Though hyaluronic acid has been used for chronic pain in the past, it may have some utility as an acute joint pain or acute exacerbations of chronic joint pain.¹⁰ Hyaluronic acid can be bound in a variety of tissues with a high concentration in synovial fluid and articular cartilage. Hyaluronic acid is a glycosaminoglycan that is nonprotein and nonsulfated. It is naturally occurring and is created by a variety of cell types, including fibroblasts, chondrocytes, and synoviocytes. The role of hyaluronic acid is diverse and includes properties such as lubrication, viscoelasticity, shock absorption, and stabilization of joints.¹¹ With particular disease, such as OA, hyaluronic acid declines notably by number and molecular weight.¹¹ The development of OA has been associated with apoptosis of chondrocytes leading to degradation of the articular cartilage matrix.¹¹

Osteoarthritis has been observed to affect various joints in the body. Most frequently affected are the feet, hands, elbow, knees, hips, and shoulders.¹¹ Prior reports have noted that giving hyaluronic acid intra-articular is more efficacious vs intravenous or oral route.¹¹ It is reported that normal human physiologic hyaluronic acid is about 0.35 g/100 mL with an MW of 4 000 000-10 000 000 Da in particular fluid. In OA, hyaluronic acid in synovial fluid is degraded and eliminated at faster rates vs nonosteoarthritic joints.¹¹

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