Complete Freund's adjuvant-induced intervertebral discitis as an animal model for discogenic low back pain

Min Lee, Byung Jo Kim, Eun Jeong Lim, Seung Keun Back, Ju-Han Lee, Sungwook Yu, Sung Ha Hong, Joo-Han Kim, Sang Heon Lee, Woon Won Jung, Dong Geun Sul, Heung Sik Na

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1287-1296
Number of pages10
JournalAnesthesia and Analgesia
Volume109
Issue number4
DOIs
Publication statusPublished - 2009 Oct 1

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Discitis
Freund's Adjuvant
Calcitonin Gene-Related Peptide
Low Back Pain
Animals
Animal Models
Intervertebral Disc
Pain
Rats
Nitric Oxide Synthase Type II
Prostaglandins E
Intervertebral Disc Degeneration
Injections
Messenger RNA
Spine
Polymerase chain reaction
Neural Pathways
Hyperalgesia
Signal processing
Spinal Ganglia

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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Complete Freund's adjuvant-induced intervertebral discitis as an animal model for discogenic low back pain. / Lee, Min; Kim, Byung Jo; Lim, Eun Jeong; Back, Seung Keun; Lee, Ju-Han; Yu, Sungwook; Hong, Sung Ha; Kim, Joo-Han; Lee, Sang Heon; Jung, Woon Won; Sul, Dong Geun; Na, Heung Sik.

In: Anesthesia and Analgesia, Vol. 109, No. 4, 01.10.2009, p. 1287-1296.

Research output: Contribution to journalArticle

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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.",
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AU - Kim, Byung Jo

AU - Lim, Eun Jeong

AU - Back, Seung Keun

AU - Lee, Ju-Han

AU - Yu, Sungwook

AU - Hong, Sung Ha

AU - Kim, Joo-Han

AU - Lee, Sang Heon

AU - Jung, Woon Won

AU - Sul, Dong Geun

AU - Na, Heung Sik

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