Corticosteroid Use in Pain Management
Corticosteroids are commonly used in the practice of pain management for their anti-inflammatory properties. These agents, produced by the adrenal cortex, are widely used in epidural, joint, peripheral nerve and various types of soft tissue injections. Corticosteroids can be classified as anti-inflammatory (glucocorticoids), androgenic/estrogenic and salt-retaining (mineralocorticoids). Despite these individual classifications, most corticosteroids have some overlapping properties with predictable adverse reactions. This article will review the mechanism of action of corticosteroids, basic properties of individual drugs, adverse reactions and applications in pain management.
Mechanism of Action
The primary mechanism of action of corticosteroids is at the cellular level. These drugs appear to bind to intracellular receptors, alter gene expression and ultimately regulate cellular processes.1,2 Their anti-inflammatory effect results from several different factors including inhibition of phospholipase, alterations in lymphocytes, inhibition of cytokine expression and stabilization of the cellular membrane. 3
The conversion of phospholipids to arachidonic acid is critical to the formation of the inflammatory mediators such as LTB-4, LTC-4, LTD-4, and LTE-4 and various prostaglandins. This initial step is facilitated by the enzymatic action of phospholipase A2.
Corticosteroids inhibit the action of phospholipase and thus prevent the formation of arachidonic acid and subsequently the inflammatory mediators.
Corticosteroids also alter the function of lymphocytes. These drugs appear to alter the chemotactactic or chemoattractant mechanism found in the inflammatory response after tissue injury.4 An apparent retention of white blood cells in the lymphatic system indirectly limits their ability to migrate to the damaged tissue.5 Lymphocytic function and availability is diminished to the point where a 70 percent reduction in circulating lymphocytes can be observed with a typical dose of the drug.6 The effects of corticosteroids on lymphocytes differ between humans and laboratory animals such as rats and mice. Following a dose of corticosteroids, a transient elevation in the white blood cell count may be observed. In the absence of infection this elevation may be attributed to the demargination of neutrocytes from the endothelium and an increased rate of cellular release from the bone marrow.7
Interleukin 1 (IL-1) and tumor necrosis factor (TNF) are integral components to the cell mediated immune response to injury. The expression of these cytokines can be effectively inhibited by corticosteroids8 IL-1 originates from macrophages, monocytes and various parenchymal cells and induce the production of endothelial based proteins. This results in thrombus formation and ultimately the activation of inflammatory and immune cells. IL-1 also affects procoagulant proteins, adhesive factors and the metabolism of arachidonic acid within the endothelial cell. TNF stimulates the production of various chemotactic mechanisms from neutrophils and granulocytic proteins.
Corticosteroids also affect the permeability of the vascular wall. This membrane stabilization effect alters fluid shifts and decreases cellular and fluid movement from the vascular space. Lysosomal enzymes are also prevented from being released.9 The end result is alteration of fluid retention at the site of tissue damage.
Many synthetic corticosteroids used in the treatment of painful conditions have been developed to optimize their anti-inflammatory properties and alter their duration of action. Glucocorticoids, with a high water affinity, are rapidly absorbed resulting in a rapid onset of action, but also quickly metabolized resulting in a short half life. When the water soluble properties of these drugs are altered, the duration of action of the drug also changes. Glucocorticosteroids are metabolized in the liver and excreted by the kidneys.
Individual agents exhibit varying properties of anti-inflammatory potency, salt retention properties, plasma half lives and duration of action (See Table 1). These agents include hydrocortisone, cortisone, prednisone, prednisolone, methylprednisolone, triamcinolone, beta-methasone and dexamethasone. The decision to use specific agents is usually based on the preference and experience of the treating clinician, drug availability and the procedure to be performed.
|AGENT||Anti-Inflammatory Potency*||Salt Retention Property||Plasma Half Life (min)||Duration**||Equivalent Oral Dose (mg)|
|Methylprednisolone (Medrol, Depo-Medrol)||5||0||180||I||4|
|Triamcinolone (Aristocort, Kenalog)||5||0||300||I||4|
|*Relative to hydrocortisone
**S=short, I=intermediate, L=long
Table 1. With Permission, Lennard, T, Fundamentals of Procedural Care, p. 6, in Lennard (ed), Physiatric Procedures in Clinical Practice, 1st edition, Hanley & Belfus, Philadelphia, 1995.