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Complete Freund's adjuvant-induced intervertebral discitis as an animal model for discogenic low back pain.
Anesth Analg. 2009 Oct; 109(4):1287-96.A&A

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-microL 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.

Authors+Show Affiliations

Department of Biomedical Science, Korea University Graduate School, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19762759

Citation

Lee, Min, et al. "Complete Freund's Adjuvant-induced Intervertebral Discitis as an Animal Model for Discogenic Low Back Pain." Anesthesia and Analgesia, vol. 109, no. 4, 2009, pp. 1287-96.
Lee M, Kim BJ, Lim EJ, et al. Complete Freund's adjuvant-induced intervertebral discitis as an animal model for discogenic low back pain. Anesth Analg. 2009;109(4):1287-96.
Lee, M., Kim, B. J., Lim, E. J., Back, S. K., Lee, J. H., Yu, S. W., Hong, S. H., Kim, J. H., Lee, S. H., Jung, W. W., Sul, D., & Na, H. S. (2009). Complete Freund's adjuvant-induced intervertebral discitis as an animal model for discogenic low back pain. Anesthesia and Analgesia, 109(4), 1287-96. https://doi.org/10.1213/ane.0b013e3181b31f39
Lee M, et al. Complete Freund's Adjuvant-induced Intervertebral Discitis as an Animal Model for Discogenic Low Back Pain. Anesth Analg. 2009;109(4):1287-96. PubMed PMID: 19762759.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Complete Freund's adjuvant-induced intervertebral discitis as an animal model for discogenic low back pain. AU - Lee,Min, AU - Kim,Byung-Jo, AU - Lim,Eun Jeong, AU - Back,Seung Keun, AU - Lee,Ju-Han, AU - Yu,Sung-Wook, AU - Hong,Sung-Ha, AU - Kim,Joo Han, AU - Lee,Sang-Heon, AU - Jung,Woon-Won, AU - Sul,Donggeun, AU - Na,Heung Sik, PY - 2009/9/19/entrez PY - 2009/9/19/pubmed PY - 2009/10/2/medline SP - 1287 EP - 96 JF - Anesthesia and analgesia JO - Anesth Analg VL - 109 IS - 4 N2 - 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-microL 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. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/19762759/Complete_Freund's_adjuvant_induced_intervertebral_discitis_as_an_animal_model_for_discogenic_low_back_pain_ L2 - https://doi.org/10.1213/ane.0b013e3181b31f39 DB - PRIME DP - Unbound Medicine ER -