2118722, 906 PM Corticosteroid Use in Pain Management CEPPM Q PPM ACCESS ‘Access to the PPM Journal and newsletters is FREE for clinicians. SIGNUP BPrint Signup for PPM 5 Articles in Volume 0, Issue #1 Chronie Tension Headache Corticosteroid Use in Pain Management Fibromyalgia Syndrome & Surface Electromyography Intraarticular Mechanisms for Pain Control Pharmaceuticals in the Pipeline - Anti-theumatic Drugs Corticosteroid Use in Pain Management ‘The basie properties, reactions and applications of corticosteroid use should be reviewed prior to tre By Ted A. Lennard, MD ting patients, 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, basie 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 ant lammatory effect results from several different factors including inhibition of phospholipase, alterations in lymphocytes, inhibition of cytokine expression and stabilization ofthe 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 LTTE-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 aso alter the function of lymphocytes. These drugs appear to alter the chemotactactic or chemoattractant mechanism found inthe inflammatory response after tissue injury.4 An apparent retention of white blood cells inthe 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 reduetion in circulating lymphocytes can be observed with atypical dose ofthe drug. 6 The effects of corticasteroids 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 hips: www practicalpainmanagement comcortcasterid-use-pain-managerent 182118722, 906 PM Corticosteroid Use in Pain Management Interleukin 1 (0 1) and tumor necrosis factor (TNF) are integral components to the cell mediated immune response to injury. The expression of these eytokines 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 eels, 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 aso affect the permeability ofthe vascular wall. This membrane stabilization effect alters fluid shifts and deereases cellular and fluid movement from the vascular space. Lysosomal enzymes are also prevented from being released.g The end result is alteration of {luid retention atthe site of tissue damage. Individual Agents 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, ae rapidly absorbed resulting ina rapid onset of action, but also quickly metabolized resulting in a short halflife, When the water soluble properties of these drugs are altered, the duration of action ofthe drug also changes. Glucocorticasteroids are metabolized in the liver and excreted by the kidneys Individual agents exhibit varying properties of anti-inflammato (See Table 1). These agents include hydrocortisone, cortisone, prednisone, prednisolone, methylprednisolone, triameinolone, beta- ‘methasone and dexamethasone. The decision to use specific agents is usually based on the preference and experience ofthe treating clinician, drug availability and the procedure to be performed. ‘Comparison of Commonly Used Glucocorticoid Steroids2,10-15 y potency, salt retention properties, plasma half lives and duration of action Equivalent Antiinflammatory Salt Retention _—_—Plasma Half a AGENT Durati Oral Dose Potoncy* Property Lite (min) (m9) Hydrocortisone (Cortisol) 1 a 90 s 20 Cortisone os 2 30 s 25 Prednisone 4 “ 60 I 5 Prednisolone 4 u 200 1 5 Methyprednisolone (Medrol ° 180 1 Depo-Medrel) . ‘ ‘Triamcinolone (Aristocort, 1 Kenalog) . * ‘ Betamethasone (Celestone) ° 100-300 L 06 Dexamethasone (Decadron) 25-90 ° 100-300 L ons *Relatve to hydrocortisone ‘*3-short, -intermediate, ‘Table 1. With Permission, Lennard, T, Fundamentals of Procedural Care, p. 6, in Lennard (ed), Physiatrie Procedures in Clinical Practice, 1st edition, Hanley & Belfus, Philadelphia, 1995. Adverse Rea A multitude of adverse reactions and a paucity of unfounded patient accounts surround the use of corticosteroids. Patients who confuse the adverse reactions of these drugs with those of anabolic steroids are often misguided by their peers who cause unnecessary fear, This fear often goes uncorrected by their physicians. Nevertheless corticosteroids, when used without caution, can eause both transient and permanent tissue damage. This potentially occurs at both the local level and systemically. Unfortunately, even when using these agents htps:www_practicalpainmanagement comcortcasterid-use-pain-managerent 282118722, 906 PM Corticosteroid Use in Pain Management ‘within recommended guidelines, adverse reactions commonly occur. This is true regardless of their route of administration, medical condition ofthe patient or the experience ofthe treating physician, As expe more likely to precipitate their known side effects than a single low dose injection. Since these drugs are metabolized in the liver and excreted by the kidney, patients with known renal or hepatic disease should be administered these drugs with caution. Local adverse reactions of corticosteroids usually occur at well localized areas in the skin, soft tissue or periarticular regions as a result of injections. Alterations in skin pigmentation can be noted in some eases when closely observed, especially in dark skinned individuals. ted, high doses and/or chronie intake of corticosteroids are Atrophy of the subeutaneous and periarticular tissue occurs where repeated injections have been given. This is commonly scen after repeat injections at both the medial and lateral epicondylar regions, the suboecipital regions after greater and lesser occipital nerve blocks or ‘rigger point injections, and occasionally in spinal regions where repeat corticosteroid containing trigger point injections are given. These effects can be diminished or eliminated by carefully flushing the needle with saline or anesthetic prior to exiting the skin with the needle, Reports of tendon rupture, tendon attrition, cartilage damage, erystal-induced arthritis and pericapsular caleification are found in the literature.a6 Systemic reactions to corticosteroids have been reported in all organ systems and are well documented in the medical literature.10-11,17, ‘The most common reported problems are fluid and electrolyte imbalances, bone demineralization, gastrointestinal disease and impaired glucose metabolism (See Table 2). In a healthy state, the fluid and electrolyte problems may be non-existent or simply result in transient swelling ofthe extremities or face. Patients often complain of transient facial flushing. Caution, however, s advised when administering ‘these drugs to patients with heart disease due to the risk of congestive heart failure. Chronic corticosteroid intake often demineralizes bone causing osteoporosis with resulting fractures common to the spine, wrist and hip. These fractures are typically seen in patients taking oral steroids such as prednisone for chronic medical conditions including respiratory disease, rheumatological disorders and skin diseases. Gastrointestinal disease, such as nausea, vomiting, diarrhea, indigestion, ulcerative colitis with impending abscess or perforation and peptic ulcer disease have been reported. Known diabeties or those with impaired glucose metabolism who receive corticosteroids will typically ‘ote a rise in serum glucose. These patients should be forewarned of this potential problem and closely monitored for changes in their serum glucose levels to make appropriate doseage adjustments in their hypoglycemic agents. Common Systemic Adverse Reactions to Corticosteroids SYSTEMIC REACTION CLINICAL SYMPTOMS Fluid & Electrolyte Disturbance Swelling, Congestive Heart Faure Bone Demineraliation Osteoporosis, Fractures Gastrointestinal Disease Hemorshage, Peptic Uleer Disease Imprired Glucose Metabolism, Elevated Glucose Levels Central Nervous System Changes Mood Swings, Nervousness, Appetite Stimulation, Steroid Psychosis ‘Table 2. Allergic reactions to corticosteroids have been reported. 18 If delayed release formulatons are given, the allergic response may not occur until one to two weeks following the doseage. These allergi reactions may be manifested as skin lesions such as rashes, hives or eruptions, or various respiratory complaints. One should be cognizant of the potential for additives and preservatives often found in corticosteroid ‘mixes to also cause these same types of allergic reactions. Caution should be used before labeling a patient allergic to a corticosteroid for, often, the symptoms may simply be an adverse reaction, One of the more serious complications from corticosteroid intake is adrenal cortical insufficiency. This condition i a result of suppression of the hypothalamic-pituitary-adrenal axis. When this axis has been suppressed, an individual's ability to respond to stressful situations such as infections or surgery is jeopardized. Although less common than the other adverse reactions listed previously, itis usually associated with chronic intake of high corticosteroid doses. One other potentially serious side effect from corticosteroid use is impaired ‘wound healing. This occurs through inhibition of eollagen synthesis and fibroblastic function.19 Concommitent drug intake should be carefully serutinized prior to preseribing or injecting a corticosteroid. A number of drug interactions ‘have been reported that often potentiate or diminish the drugs clearance and half-lives. Non-steroidal anti-inflamnmatory drugs, oral contraceptives and other exogenous estrogens are known to increase the potency of corticosteroids. Macrolide antibiotics such as htps:ww-practicalpainmanagement comcortcasterid-use-pain-managerent ae2118722, 906 PM Corticosteroid Use in Pain Management erythromycin and azithromycin may increase the potency of methylprednisolone by decreasing its clearance. In contrast rifampin, phenobarbital, earbamazepine, and phenytoin often increase drug clearance and decrease the anti-inflammatory effect ofthe corticosteroid, Oral anti-coagulants and theophylline have varying effects.15 The physician would be prudent in making doseage adjustments accordingly ‘when patients are discovered to be consuming these drugs. Application in Pain Management ‘The use of corticosteroids is widespread in pain management. These drugs may diminish or eliminate a painful foci by virtue oftheir anti- inflammatory properties. These medications are commonly administered by either an oral or injectable route. ‘The use of oral corticosteroids has been accompanied by controversy in pain mnanagement. These agents clearly reduce pain and result in a higher Ievel of function when used judiciously in patients with chronic painful conditions such as theumatoid arthritis, mixed connective ‘tissue disease and skin diseases. However, when used for chronie pain syndromes with localized joint, nerve or disc disease the functional improvements are less common and alternative drugs are often the choiee.20 Their efficacy inthe treatment of acute back pain has also een questioned.20 ‘The use of injectable corticosteroids is more common to the pain management clinician, especially with musculoskeletal and peripheral neurological pain conditions. Considerable training is commonplace and necessary forthe clinician to learn injectable procedures in order to place a corticosteroid or anesthetic into a desired target site. This may include injections into the intra-articular space, trigger point, ligament, peritendon region, perineural region and the epidural space. The use of fluoroscopy has now made it easier and common for most areas in the axial and appendicular skeleton to be accessed by needle injection. When these precise injections are administered, in combination with small doses of anesthetics, diagnosistic information regarding one's pain generator can also be obtained. Fy jural Injections Epidural steroid injeetions are considered standard in the non-operative treatment of many cervical, thoraeie and lumbosacral spinal disorders. This indudes midline, paramedian and transforaminal approaches. Inthe lumbosaeral region, a caudal or trans-saeral approach can also be used. Each of these approaches require considerable skill and manual dexterity and carry unique risks. These are well described in other sources.21 Although not without controversy, epidural steroid injections are used worldwide with varying results for the ‘management of the painful spine.22-26 When used in the framework of a compre! diminish a patient's pain while allowing them to increase their level of function. Otherwise, without localized adequate pain relief functional issues cannot be addressed and the patient remains focused on the pain treatment phase of rehabilitation. “The indications for corticosteroid use are extensive, but often met with controversy and misunderstanding.” Epidural injections are used in most painful spinal conditions inciuding a multitude of dise abnormalities: herniations, bulges, internal dise ensive rehabilitation program, these procedures often disruption, degeneration, ete, as well as stenosis and radiculopathies. The route of administration of the corticosteroid is usually dictated, by the patient's symptoms and the underlying differential diagnosis. These procedures can also be used to assist in the diagnosis ofa painful disc or nerve root. Anesthe-tic is added to the corticosteroid solution and injected selectively following contrast dye confirmation under ‘uoroscopy. The patient's preinjection condition is then compared to the postinjection condition. Response to transforaminal injections has been shown to have surgical predictive values.27 Joint Injections Corticosteroids have long been used in the treatment of painful appendicular and axial joint pain. They have been used on patients with degenerative joint disease, rheumatoid arthritis, localized cartilage damage and nonspecific joint pain. Using fluoroscopy and contrast dye confirmation, the sacro-iliac and spinal zygo-apophyseal (facet) joints can also be injected. Various mixtures of anesthetic and corticosteroid solutions are used. Typically, small size joints, such as the spinal facet joints, are injected with 1-2 ees of volume with a 1:1 ratio of corticosteroid to anesthetic, Medium size joints such as the elbow or wrist may require 2-4 ces of solution. Larger joints, such as the knee, hip and sacro-iliac joints, may require 4-8 ees of corticosteroid and anesthetic solution with 2 ees of eo swith anesthetic. steroid and the remainder Soft Tissue Inject Soft tissue injections encompass the wide category of injections into muscle (trigger points), ligaments and peritendons. Perhaps the most common type of injections for pain, these structures are very amenable to needling, As with other types of injections, corticosteroids are commonly mixed with anesthetics and injected in small aliquots into muscle, ligaments or around tendon structures, When injecting trigger points, one often uses the above combinations or ean perform dry needling techniques.28 These injections are often given in conjunction with a well designed stretching program. Perineural Injections htps:www_practicalpainmanagement comcortcasterid-use-pain-managerent 4082118722, 906 PM Corticosteroid Use in Pain Management Perineural injections or nerve blocks are frequently given for neurogenic pain. These injections are primarily anesthetic in composition, but often corticosteroid will be added. These procedures are commonly used to assist in the diagnosis of a painful region, For example, if one suspects a spinal facet joint to be the putative source of pain, the medial branch (MB) of the posterior primary ramus of the spinal nerve ‘hat innervates that joint can be blocked and the patient's response recorded. This may lead the pain management clinician to conclude the basis ofthe patient’s spinal pain and may ultimately recommend additional procedures such as radiofrequency lesioning to that MB. In other cases a peripheral nerve may be supect as a patient's primary source of pain, ie, inflammatory neuritis, cubital tunnel syndrome, carpal tunnel syndrome, ete, and a corticosteroid may be injected adjacent to the nerve involved. Care should be taken that an intraneural injection is avoided. (See Figure 2) (ues: /fwnw:prctcalpainmanagemen.com/sts/ defen es/imagecache/ightbox large/inport_ files hal Po009Fo2/fs. pm) FIGURE 1. The needle tip should be placed in the extra-fasicular space of the peripheral nerve to avoid. {ntraneural injury. JMustration by Suzanne B. Lennard Conclusion ‘The use of corticosteroids is widespread among pain management clinicians. One should be familiar with their mechanism of aetion, basic drug properties, adverse reactions and use with injections. The indications for corticosteroid use are extensive, but often met with controversy and misunderstanding, Clinicians should educate their patients and peers on the judicious and proper use of corticosteroids. View Sources (/cortiostrid-se-pan-managementsteiset) 1. Boumpas DT, Paliogianni F, Anastassiou ED, et al. Glucocorticosteroid action on the immune system, Molecular and cellular aspects. Clin Exp Rheumatol 9:413-423, 1991 2. Goldfien A: Adrenocorticosteroids and adrenocortical antagonists. In Kataung BG (ed): Basic and Clinical Pharmacology, 2nd ed. Los Atos, CA, Lange Medical Publishers, 1984, pp 459-465, 3. Gallin JL, Goldstein IM, Snyderman R. Overview, In Gallein JI, Goldstein IM, Synderman R (eds). Inflammation: Basie Principals in Clinical Correlates. New York, Raven, 1992, pp 1-4 4. Fantone J. Basic concepts of inflammation. In Leadbetter WB, Buckwalter JA, Gordon SL (ed). Sports Induced Inflammation. Parkridge, TL, American Academy of Orthopedic Surgeons, 1990, pp 25-53. 5. Peters WP, Holland JF, Senn H, et al. Corticosteroid administration and localized leukocyte mobilization in man. N Engl J Med 286:342- 345, 1972, 6. Fauci AS, Dale DC. The effect of in vivo hydrocortisone on subpopulations of human lymphocytes. J Clin Invest 53:240-246, 1974. 7. Fauci AS, Dale DC, Balow JE. Glucocorticosteroid therapy: Mechanism of action and clinical considerations, Ann Intern Med 84:304-315, 1976. 8, Crabtree GR, Gillis S, Smith KA, Munck A, Glucocorticoids and immune responses. Arthritis Rheum 22:1246-1256, 1979. 9. Behrens TW, Goodwins JS. Oral corticosteroids. In Leadbetter WB, Buckwalter JA, Gordon SL (eds). Sports Induced Inflammation. Brockridge, IL, American Academy of Orthopedie Surgeons, 1990, pp 405-419. 10, Claman HN. Ghicocorticosteroids II: The clinical responses. Hosp Pract 143-151 1983. htps:www_practicalpainmanagement comcortcasterid-use-pain-managerent se2118722, 906 PM Corticosteroid Use in Pain Management 11, George B, Kirwan JR. Corticosteroid therapy in rheumatoid arthritis. Ballieres Clin Rheumatol 4:621-646, 1990. 263, 1983, 13. Gustuvson LE, Benet LZ, Pharmacokineties of natural and synthetic glucocorticoids. In Anderson DC, Winter JSD (eds). Adrenal Cortex. London, Butterworth, 1985, pp 235-281. 14, Holland EG, Taylor AT. Glucocorticoids in clinical practice. J Fam Pract 32:512-519, 1991. 15. Olin BR. Hormones: Adrenal corticosteroids. In Olin BR (ed): Drug Facts and Comparisons. St. Louis, Wolters Kluwer, 1993, pP 465 486, 16, Gottlieb NL, Riskin WG. Complications of local corticocosteroid injections. JAMA 249:1547-2548, 1980. 17. Kehr] JH, Fauei AS. The clinical use of glucocorticoids. Ann Allergy 50:2-10, 1983. 18. Dreyer, $, Commonly Used Medications in Pain Procedures, n (ed) Lennard, TA, Pain Procedures in Clinical Practice, 2nd Ed, Hanley & Belfus, Philadelphia, 2000, pp 1-9. 19. Peacock PE Jr, Van Winkler W Jr. Surgery and Biology of Wound Repair. Philadelphia, WB Saunders, 1979, p. 128, 20. Deyo, RA, Drug Therapy for Back Pain, Which Drugs Help Which Patients?, Spine 21(24), pp 2840-2850, 1996. 2, Woodward, J, Herring, S, Windsor, R, Epidural Procedures in Spine Pain Management, in Lennard (ed), Pain Procedures in Clinical 12, Gray RG, Gottlieb NL. Tntra-articular corticosteroids, basie science and pathology. Clin Orthop Rel Res 177:235: Practice, ond ed, Hanley & Belfus, Philadelphia, 2000, 22. Hopayian K, Mugford M. Conflicting conclusions from two systematic reviews of epidural steroid injections for sciatica: which evidence should general practitioners heed? British J Gen Prac, Jan 1999, pp 57-60. 23, Devulder J, Transforaminal Nerve Root Sleeve Injection with Corticosteroids, Hyaluronidase, and Local Anesthetic in the Failed Back 54, 1998. ‘24. Bogduk, N, Spine Update in Epidural Steroids, Spine 20(7) pp 845-848, 1995. 25. Ridley MG, Kingsley GH, Gibson T, etal. Outpatient lumbar epidural corticosteroid injection in the management of sciatica Br J Rheumatol 27:295-299, 1988, 26, Bush K, Hillier S. A controlled study of caudal epidural injections of triamcinolone plus procaine for the management of intractable Surgery Syndrome, J Spinal Disorders, 11(2), pp 151-3 sciatica, Spine 16:572-575, 1991 27. Herron LD. Selective nerve root block in patient seleetion for lumbar surgery ~ surgical results. J Spinal Disord 2:75-79, 1989. 28. Fischer A, Trigger Point Injection, in Lennard (ed) Pain Procedures in Clinical Practice, Hanley & Belfus, Philadelphia, Last updated on: January 28, 2012 Subseribe to "Pain Monitor", a PPM eNewsletter for HCPs Ifyou are not a healthcare professional to subscribe to our patient newsletter. Practical Pain Management is a Remedy Health Medi, L1.C web property. 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