The sensation of pain is the result of complex interactions that involve all levels of the nervous system, from sensory input to the dorsal horn of the spinal cord to brain structures like the medulla and midbrain [1]. Corticosteroids play a crucial role in nociceptive transmission by altering the expression of neuropeptides involved with pain signaling at the spinal cord level [1].
The mechanism of action of corticosteroids largely involves cytokine suppression [2]. Proinflammatory cytokines enhance activation and migration of immunocytes, which can result in degeneration and pain [2]. By inhibiting phospholipase A2 and the arachidonic acid metabolic pathway, corticosteroids minimize the production and release of proinflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-alpha [4]. Corticosteroids also enhance the inhibition of certain transcription factors, which aids in decreasing expression of proinflammatory genes [2]. As a consequence, corticosteroids are considered to be the most effective treatment against inflammatory pain [3].
Over the past 30 years, corticosteroids have been used in the management of various conditions, including spinal cord compression, superior vena obstruction, increased intracranial pressure, bowel obstruction, and osteoarthritis [2]. Accepted routes of corticosteroid administration are oral, intramuscular, intravenous, transcutaneous, and neuraxial [2]. The most often prescribed corticosteroid for pain treatment is dexamethasone, which can be given orally or intravenously [3].
A number of studies have documented the beneficial effects of corticosteroids on cancer pain management [3]. Pain is a major issue in cancer, as it occurs in 30-50% of patients in earlier stages and in 70-90% of patients with advanced disease [3]. Several studies suggest that corticosteroids may be effective in the treatment of bone and neuropathic pain when administered along with other analgesics [3]. Dexamethasone is most commonly used for cancer pain management due to its high potency, long duration of action, and minimal mineralocorticoid effect [3]. The recommended starting daily dose is 8 mg with subsequent adjustments to achieve optimal analgesia [3].
Additionally, randomized trials have shown that low, short-dose corticosteroid regimens are safe and effective methods for reducing postoperative pain [1]. A 2004 study found that single intravenous doses of the corticosteroid methylprednisolone significantly reduced pain when administered on the first day after orthopedic surgery [4]. Similarly, a 2018 meta-analysis reported that the corticosteroid prednisolone effectively reduced postoperative pain between 12 and 24 hours after knee arthroplasty [5]. Other beneficial effects of corticosteroid administration include reduced postoperative nausea and vomiting [4].
The use of corticosteroids for pain relief does come with potential side-effects [3]. Immediate adverse effects may include immunosuppression, which can present as candidiasis, hyperglycemia, and psychiatric disorders [3]. These reactions are typically seen within the first two weeks of treatment but may appear as soon as the first day [6]. Potential long-term effects consist of myopathy, peptic ulceration, osteoporosis, and Cushing’s syndrome [3]. As a result, patients receiving corticosteroid therapy should always be given the lowest effective dose [3]. Lastly, corticosteroids should never be prescribed with NSAIDs, as the combination increases the risk of gastric bleeding 15-fold [3].
References
- McEwen, B., & Kalia, M. (2010). The role of corticosteroids and stress in chronic pain conditions. Metabolism, 59, S9-S15. doi:10.1016/j.metabol.2010.07.012
- Knezevic, N. N., Jovanovic, F., Voronov, D., & Candido, K. D. (2018). Do corticosteroids still have a place in the treatment of chronic pain?. Frontiers in Pharmacology, 9, 1229. doi:10.3389/fphar.2018.01229
- Leppert, W., & Buss, T. (2012). The Role of Corticosteroids in the Treatment of Pain in Cancer Patients. Current Pain and Headache Reports, 16(4), 307-313. doi:10.1007/s11916-012-0273-z
- Gilron, I. (2004). Corticosteroids in postoperative pain management: Future research directions for a multifaceted therapy. Acta Anaesthesiologica Scandinavica, 48(10), 1221-1222. doi:10.1111/j.1399-6576.2004.00581.x
- Mohammad, H., Hamilton, T., Strickland, L. et al. (2017). Perioperative adjuvant corticosteroids for postoperative analgesia in knee arthroplasty. Acta Orthopaedica, 89(1), 71-76. doi:10.1080/17453674.2017.1391409
- Watanabe, S., & Bruera, E. (1994). Corticosteroids as adjuvant analgesics. Journal of Pain and Symptom Management, 9(7), 442-445. doi:10.1016/0885-3924(94)90200-3