What is the role of inflammatory factors in the pathophysiology of low back pain (LBP) and sciatica?

Updated: Aug 22, 2018
  • Author: Jasvinder Chawla, MD, MBA; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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Answer

Inflammatory factors may be responsible for pain in some cases in which epidural steroid injections provide relief. Corticosteroids inhibit the production of arachidonic acid and its metabolites (prostaglandins and leukotrienes), inhibiting phospholipase A2 (PLA2) activity. PLA2 levels, which play a role in inflammation, are elevated in surgically extracted samples of human herniated disks. Furthermore, PLA2 may play a dual role, inciting disk degeneration and sensitizing annular nerve fibers. Afferent nociceptors in nerve roots may be sensitive to various proinflammatory mediators, which are inhibited by corticosteroids, such as prostanoids produced from arachidonic acid and released from cell membrane phospholipids by PLA2.

Research suggests that proinflammatory cytokines may also contribute to diskogenic pain by sensitizing nociceptors and disk degeneration by suppressing proteoglycan synthesis and increasing diskal matrix degradation. Cytokines are produced in response to neural injury in the CNS and may play a role in spinal neural hypersensitization and chronic neuropathic pain. Cytokines known to play a role in nociception include nerve growth factor, interleukin (IL)-1, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α). [30]

Corticosteroids can inhibit activity of TNF-α, which induces IL-1 and prostaglandin E2 production. Once released, these substances contribute to early and late effects of the inflammatory process and stimulate nociception. A nociceptive role for nitric oxide (NO) in diskogenic pain syndromes is under investigation. NO levels are elevated in human disk herniations and when the hydrostatic pressure of the disk is increased due to biomechanical stressors. NO inhibits proteoglycan synthesis in cells in the nucleus pulposus, leading to proteoglycan loss, reduced water content, and disk degeneration.


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