Techniques in Regional Anesthesia and Pain Management
The mechanism of action and side effects of epidural steroids
Section snippets
Inflammatory theory
Back pain is mediated by various pathways leading to the formation of numerous inflammatory mediators. Phospholipase A2 is an inflammatory enzyme found in high concentrations in the human intervertebral disc, which may play a critical role in many pathologic conditions resulting in back pain.2 Phospholipase A2 is the enzyme responsible for the conversion of membrane phospholipids into arachidonic acid, and subsequently controls the pathways involving cyclooxygenase and lipoxygenase, leading to
Mechanism of action of NSAIDs and steroids
Whereas nonsteroidal anti-inflammatory drugs (NSAIDs) exert their analgesic effect on the cyclooxygenase pathway, thereby reducing the production of inflammatory prostaglandins, steroids primarily exert their inhibitory function primarily via the lipoxygenase pathway to reduce the downstream formation of leukotrienes. Cells exposed to glucocorticoids (GCs) synthesize and release a phospholipase A2-inhibitory glycoprotein, also termed lipomodulin. The inhibitory action of lipomodulin in turn
Anatomical contribution to transmission of pain
On the gross, anatomical level, numerous structures of the spine are capable of transmitting back pain. The intervertebral discs, nerve root dura, facet joints, ligaments, fascia, and muscles are all tissues that transmit pain in the low back and lower extremities. Sciatica-like pain can be generated by pressure on the annulus fibrosus, posterior longitudinal ligament, and swollen, stretched, or compressed nerve roots.7 Spinal radicular pain results from neural compression causing dysfunction,
Direct nociceptive action of steroids
Whereas the anti-inflammatory theory of is supported by numerous studies, the action of corticosteroids on the direct transmission of pain is less well studied. Corticosteroids have been shown to produce direct electrophysiological effects on pain fibers and alter the conductivity in the neuromuscular junction and neurons. Blockade of nociceptive C-fiber conduction is another proposed mechanism of corticosteroid conduction.11, 17 Johansson and coworkers studied the direct effect of
Steroids and 5-hydroxytryptamine
Another proposed mechanism by which corticosteroids may exert their analgesic effects is by interaction with norepinephrine (NE) and 5-hydroxytryptamine (5-HT) neurons in the dorsal horn substantial gelatinosa, which are known to be involved in the transmission of pain. Studies dating back to 1985 demonstrated that GC receptor immunoreactive nerve cells were mainly found in the area of the noradrenaline, adrenaline, and 5-HT cell groups of the lower brain stem, and of the substantia gelatinosa
Other mechanisms of analgesia
Even before steroids were injected epidurally, it was demonstrated that the instillation of large volumes of saline solution could alleviate back pain. Studies have shown a similar benefit from the injection of saline or local anesthetics, without corticosteroids. It is presumed that the probable benefit of saline injection is through the osmotic dilution of epidural inflammatory mediators.1 In studies dating back to 1925, it was shown that the overall volume of injectant (100 mL or more with
Systemic side effects of steroid use
Epidural steroids are known to cross into systemic circulation23 and can exert many systemic side effects, just as is seen using intravenous or parenteral steroids. As listed in Table 2, virtually every bodily system is affected by the long-term use of steroids. Among the most concerning side effects in the population that often benefits from ESIs are diabetes, hypertension, and osteoporosis. Although the desired anti-inflammatory properties of GCs are primarily mediated by repression of gene
Steroids and diabetes
Studies have demonstrated an association between cortisol excess and insulin resistance.24, 25, 26 ESIs themselves have also been shown to cause hyperglycemia. A study by Younes and coworkers looked at 18 patients with and without diabetes and noted a significant increase in postprandial blood glucose at 1 day after ESI, but not after 7 or 21 days. This increase was noted to be greater in patients with diabetes.27 Ward and coworkers looked at the effect of epidural GC administration on insulin
Steroids and hypertension
High cortisol levels are associated with hypertension,24 and hypertension has been noted following ESI.27 The use of dexamethasone has similarly been associated with an increase in systolic blood pressure, whereas it had no effect on diastolic blood pressure.29 Hypertension caused by the therapeutic use of GCs occurs more often in patients receiving higher doses of GCs and is more commonly seen in elderly patients and in patients with a positive family history of essential hypertension.7
Steroids and osteoporosis
Osteoporosis is another concerning side effect of steroid use. GCs may induce bone loss by stimulating osteoclast-mediated bone resorption and reducing osteoblast-mediated bone formation, and through direct effects on calcium metabolism and sex hormones.3Figure 4 outlines the various ways by which GCs cause osteoporosis. In addition to the effect on osteoblasts and osteoclasts, GCs decrease gastrointestinal absorption and increase urinary excretion of calcium, reduce the overall number of bone
Conclusions
In review, the ways in which ESIs exert their analgesic properties are evident in numerous mechanisms. Most notably, steroids have anti-inflammatory properties, particularly via their inhibitory actions in the phospholipase A2 pathway, and they also act as modulators in the inflammatory response. Steroids may also act directly on pain fibers, as analgesics in their own right. Interactions between steroids and NE and 5-HT neurons in the dorsal horn may also be involved with the analgesic
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