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Ushirozako H, Yoshida G, Togawa D, et al. Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study. Spine Surg Relat Res. 2019;3(4):368-376doi: 10.22603/ssrr.2018-0110.
Ushirozako, H., Yoshida, G., Togawa, D., Omura, T., Hasegawa, T., Yamato, Y., Banno, T., Arima, H., Oe, S., Mihara, Y., Yamada, T., Natsume, T., Ogawa, S., Awaga, Y., Takamatsu, H., & Matsuyama, Y. (2019). Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study. Spine surgery and related research, 3(4), 368-376. https://doi.org/10.22603/ssrr.2018-0110
Ushirozako, Hiroki, et al. "Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study." Spine surgery and related research vol. 3,4 (2019): 368-376. doi: https://doi.org/10.22603/ssrr.2018-0110
Ushirozako H, Yoshida G, Togawa D, Omura T, Hasegawa T, Yamato Y, Banno T, Arima H, Oe S, Mihara Y, Yamada T, Natsume T, Ogawa S, Awaga Y, Takamatsu H, Matsuyama Y. Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study. Spine Surg Relat Res. 2019 Apr 05;3(4):368-376. doi: 10.22603/ssrr.2018-0110. eCollection 2019. PMID: 31768458; PMCID: PMC6834467.
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Spine Surg Relat Res. 2019 Apr 05;3(4):368-376. doi: 10.22603/ssrr.2018-0110. eCollection 2019.

Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study.

Spine surgery and related research

Hiroki Ushirozako, Go Yoshida, Daisuke Togawa, Takao Omura, Tomohiko Hasegawa, Yu Yamato, Tomohiro Banno, Hideyuki Arima, Shin Oe, Yuki Mihara, Tomohiro Yamada, Takahiro Natsume, Shinya Ogawa, Yuji Awaga, Hiroyuki Takamatsu, Yukihiro Matsuyama

Affiliations

  1. Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  2. Department of Orthopedic Surgery and Division of Geriatric Musculoskeletal Health, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  3. Pharmacology Group, Hamamatsu Pharma Research, Inc., Hamamatsu, Japan.

PMID: 31768458 PMCID: PMC6834467 DOI: 10.22603/ssrr.2018-0110

Abstract

INTRODUCTION: There is currently a lack of translatable, preclinical models of low back pain (LBP). Chymopapain, a proteolytic enzyme used to treat lumbar intervertebral disc (IVD) herniation, could induce discogenic LBP. The current study developed a behavioral model of discogenic LBP in nonhuman primates. Significant brain activation is observed in clinical LBP. Thus, the current study also sought to define brain activation over time in a macaque with discogenic LBP.

METHODS: Responses to pressure applied to the back at L4/L5 were measured in eight adult male

RESULTS: The mean (±SD) response pressure before treatment was 1.4 ± 0.1 kg. One day after chymopapain treatment, the response pressure decreased to 0.6 ± 0.05 kg (P < 0.01), suggestive of pressure hypersensitivity. Over time, the pressure thresholds following chymopapain treatment gradually returned to normal. Following aspiration only, the response pressure was 1.4 ± 0.05 kg, which was not significantly different from the uninjured controls. There was activation of the secondary somatosensory cortex and insular cortex one and three days after chymopapain treatment; there was no activation following aspiration only.

CONCLUSIONS: Enzymatic treatment of the nucleus pulpous leads to acute LBP and pressure-evoked activation in pain-related brain areas. The current model of discogenic LBP parallels clinical LBP and could be used to further elaborate the mechanism of acute LBP.

Copyright © 2019 by The Japanese Society for Spine Surgery and Related Research.

Keywords: brain activation; chymopapain; discogenic low back pain; functional magnetic resonance imaging; insular cortex; nonhuman primate; pressure test; secondary somatosensory cortex

Conflict of interest statement

Conflicts of Interest: There are no relevant financial interests outside of the current study. H.T., Y.A., S.O., and T.N. are employees of Hamamatsu Pharma Research, Inc.

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