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ANALGESIA

Complete Freund’s Adjuvant-Induced Intervertebral Discitis as an Animal Model for Discogenic Low Back Pain

Min Lee, MSc^*, Byung-Jo Kim, MD, PhD, Eun Jeong Lim, MSc, Seung Keun Back, PhD, Ju-Han Lee, MD, PhD, Sung-Wook Yu, MD, PhD, Sung-Ha Hong, MSc, Joo Han Kim, MD, PhD^|, Sang-Heon Lee, MD, PhD^¶, Woon-Won Jung, PhD^#, Donggeun Sul, PhD^*, and Heung Sik Na, MD, PhD

From the *Department of Biomedical Science, Korea University Graduate School; Departments of Neurology, Physiology, Pathology, |Neurosurgery, and ¶Rehabilitation Medicine, Korea University College of Medicine; and #Clinical Genomic Institute, Korea University College of Health Science, Seoul, Korea.

Address correspondence and reprint requests to Heung Sik Na, MD, PhD, Department of Physiology, Korea University College of Medicine, 126-1, Anam-dong 5 ga, Seongbuk-gu, Seoul 136-701, Korea. Address e-mail to hsna{at}korea.ac.kr.

Abstract

BACKGROUND: Although numerous animal models for low back pain associated with intervertebral disk (IVD) degeneration have been proposed, insufficient data have been provided to make any conclusions regarding pain. Our aim in this study was to determine the reliability of complete Freund’s adjuvant (CFA) injection into the rat spine as an animal model representing human discogenic pain.

METHODS: We studied IVD degenerative changes with pain development after a 10-µL CFA injection into the L5-6 IVD of adult rats using behavioral, histologic, and biochemical studies. Serial histologic changes were analyzed to detect degenerative changes. Expression of calcitonin gene-related peptide (CGRP), prostaglandin E (PGE), and inducible nitric oxide synthase (iNOS) were determined using immunohistochemistry or real-time polymerase chain reaction as support data for pain development. In addition, CGRP immunoreactivity (ir) at the IVD was considered indirect evidence of neural ingrowth into the IVD.

RESULTS: There was a significant increase of the hindpaw withdrawal response in the CFA group until 7 wk postoperatively (P < 0.05). Histologic analyses revealed progressive degenerative changes of the disks without any damage in adjacent structures, including nerve roots. In the CGRP-ir staining study, the bilateral dorsal horns and IVD had positive ir after intradiscal CFA injection. CGRP mRNA expression was increased in the dorsal root ganglion (DRG) at 2 and 4 wk, whereas PGE and iNOS mRNAs were markedly increased at 2 wk. The increment of CGRP expression was higher in allodynic rats compared with nonallodynic rats.

CONCLUSION: Intradiscal CFA injection led to chronic disk degeneration with allodynia, which was suggested by pain behavior and expression of pain-related mediators. The increment of CGRP, PGE, and iNOS also suggest pain-related signal processing between the IVD and the neural pathway in this animal model. This animal model may be useful for future research related to the pathophysiology and development of novel treatment for spine-related pain.