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Increased Interleukin-1α and Prostaglandin E2 Expression in the Spinal Cord at 1 Day After Painful Facet Joint Injury: Evidence of Early Spinal Inflammation

Kras, Jeffrey V. BS*; Dong, Ling PhD*; Winkelstein, Beth A. PhD*,†

doi: 10.1097/BRS.0000000000000107
Basic Science

Study Design. This study used immunohistochemistry and an enzyme immunoassay to quantify interleukin-1α (IL-1α) and prostaglandin E2 (PGE2) levels in the spinal cord of rats at 1 day after painful cervical facet joint injury.

Objective. The objective of this study was to determine to what extent spinal inflammation is initiated early after a painful loading-induced injury of the C6–C7 facet joint in a rat model.

Summary of Background Data. A common source of neck pain, the cervical facet joint is susceptible to loading-induced injury, which can lead to persistent pain. IL-1α and PGE2 are associated with joint inflammation and pain, both locally in the joint and centrally in the spinal cord. Joint inflammation has been shown to contribute to pain after facet joint injury. Although spinal neuronal hyperactivity is evident within 1 day of painful facet injury, it is unknown if inflammatory mediators, such as IL-1α and PGE2, are also induced early after painful injury.

Methods. Rats underwent either a painful C6–C7 facet joint distraction or sham procedure. Mechanical sensitivity was assessed, and immunohistochemical and enzyme immunoassay techniques were used to quantify IL-1α and PGE2 expression in the spinal cord at day 1.

Results. Both IL-1α and PGE2 were significantly elevated (P≤ 0.04) at day 1 after painful injury. Moreover, although both spinal IL-1α and PGE2 levels were correlated with the withdrawal threshold in response to mechanical stimulation of the forepaw, this correlation was only significant (P = 0.01) for PGE2.

Conclusion. The increased expression of 2 inflammatory markers in the spinal cord at 1 day after painful joint injury suggests that spinal inflammation may contribute to the initiation of pain after cervical facet joint injury. Further studies will help identify functional roles of both spinal IL-1α and PGE2 in loading-induced joint pain.

Level of Evidence: N/A

Spinal levels of interleukin-1α (IL-1α) and prostaglandin E2 (PGE2) were quantified 1 day after a painful C6–C7 cervical facet joint injury in the rat. Expression of both IL-1α and PGE2 increased after injury over sham, yet only PGE2 levels correlated with pain, suggesting its putative role in early regulation of joint pain.

Departments of *Bioengineering and

Neurosurgery, University of Pennsylvania, Philadelphia, PA.

Address correspondence and reprint requests to Beth A. Winkelstein, PhD, Department of Bioengineering, University of Pennsylvania, 210 S. 33rd St, 240 Skirkanich Hall, Philadelphia, PA 19104-6392; E-mail:

Acknowledgment date: June 7, 2013. First revision date: September 11, 2013. Acceptance date: October 24, 2013.

The manuscript submitted does not contain information about medical device(s)/drug(s).

The National Institutes of Health/National Institute of Arthritis, Musculoskeletal and Skin Diseases (AR056288) grant funds were received in support of this work.

Relevant financial activities outside the submitted work: grants, patents, royalties.

© 2014 by Lippincott Williams & Wilkins