Steroid injections are commonly used by interventional pain physicians to manage pain, inflammation, and other symptoms associated with various conditions, including spinal and peripheral blocks.

Steroids typically function by inhibiting the rate-limiting step carried out by the enzyme PLA2, which releases arachidonic acid from cell membranes. Arachidonic acid then participates in the activation of cyclo-oxygenase (blocked by non-steroidal anti-inflammatory drugs) and the production of lipoxygenase enzymes. These enzymes subsequently increase the levels of hyperalgesic prostaglandins, thromboxanes, and leukotrienes, all of which contribute to inflammation and pain. Additionally, steroids are believed to have actions beyond their effects on the inflammatory cascade. Methylprednisolone, for example, has been shown to inhibit transmission in thin unmyelinated C-fibers while not affecting myelinated Aβ fibers, likely due to a direct membrane-stabilizing effect rather than an indirect action through mediators. These combined direct and indirect effects reduce intraneural edema and venous congestion, thereby alleviating ischemia and improving pain.

Currently, particulate steroids (methylprednisolone acetate, triamcinolone, betamethasone) as well as non-particulate (dexamethasone) are the commonest formulations utilised in pain management. A study by Derby and colleagues documented the size and aggregation of corticosteroids used in epidural injections. They found that only dexamethasone and methylprednisolone have particles consistently smaller than a red blood cell (7.5–7.8 µm) but noted that methylprednisolone tends to aggregate and pack densely, potentially causing emboli and blocking small arterioles, whereas dexamethasone does not. It is also noteworthy that dexamethasone is a water-soluble preparation (thus it can be administered intravenously), while methylprednisolone is a suspension. Although dexamethasone is technically particulate, it is generally deemed safer because it is water-soluble, does not aggregate densely, and is considered non-particulate in the context of chronic pain management.

Potential side effects include local tissue atrophy, increased blood sugar levels, and potential systemic effects with repeated use such as adrenal suppression, osteoporosis and increased risk of infection. Spinal cord injuries have been reported following cervical and lumbar transforaminal injections. Various mechanisms have been proposed for these injuries, including direct trauma to the cord, infarction of the cord from the injection of particulate steroid suspension into the vertebral artery or a radicular or communicating artery, compression of the cord due to epidural hematoma or abscess, and infarction caused by vascular spasm or compression of vasculature after the injection of a large volume of injectate. The prevailing hypothesis suggests that the injection of particulate steroid suspension into a small artery leads to the development of anterior spinal artery syndrome, making it difficult to rule out intra-arterial placement with contrast. No serious complications have been linked to the use of non-particulate steroids. Current guidelines suggest that below the level of L3 the vascular risk is smaller, and that particulate steroids still have a place.

Although steroid formulations are a valuable tool in the management of pain and inflammation for the interventional pain physicians, the selection of the appropriate steroid formulation requires careful consideration to avoid potential complications and side effects.

References

1. Kim SJ, Park JM, Kim YW, Yoon SY, Lee SC. Comparison of particulate steroid injection vs nonparticulate steroid injection for lumbar radicular pain: a systematic review and meta-analysis. Arch Phys Med Rehabil. Published online January 17, 2024. doi:10.1016/j.apmr.2024.01.002

2. 2.Cohen SP, Greuber E, Vought K, Lissin D. Safety of epidural steroid injections for lumbosacral radicular pain: unmet medical need. Clin J Pain. 2021;37(9):707-717. doi:10.1097/AJP.0000000000000963

3. 3.Neil Collighan, Sanjeeva Gupta, Epidural steroids, Continuing Education in Anaesthesia Critical Care & Pain, Volume 10, Issue 1, February 2010, Pages 1–5, https://doi.org/10.1093/bjaceaccp/mkp043

4. 4.Derby R, Lee S-H, Date ES, Lee J-H, Lee C-H. Size and aggregation of corticosteroids used for epidural injections. Pain Med 2008;9:227–34.

5. 5.Van Boxem K, Rijsdijk M, Hans G, et al. Safe use of epidural corticosteroid injections: recommendations of the WIP Benelux Work Group. Pain Pract. 2019;19(1):61-92. doi:10.1111/papr.12709