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

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

Journal

Spine surgery and related research
ISSN: 2432-261X
Titre abrégé: Spine Surg Relat Res
Pays: Japan
ID NLM: 101718059

Informations de publication

Date de publication:
2019
Historique:
received: 11 12 2018
accepted: 10 03 2019
entrez: 27 11 2019
pubmed: 27 11 2019
medline: 27 11 2019
Statut: epublish

Résumé

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

Identifiants

pubmed: 31768458
doi: 10.22603/ssrr.2018-0110
pmc: PMC6834467
doi:

Types de publication

Journal Article

Langues

eng

Pagination

368-376

Informations de copyright

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

Déclaration de conflit d'intérêts

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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Auteurs

Hiroki Ushirozako (H)

Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Go Yoshida (G)

Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Daisuke Togawa (D)

Department of Orthopedic Surgery and Division of Geriatric Musculoskeletal Health, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Takao Omura (T)

Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Tomohiko Hasegawa (T)

Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Yu Yamato (Y)

Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Tomohiro Banno (T)

Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Hideyuki Arima (H)

Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Shin Oe (S)

Department of Orthopedic Surgery and Division of Geriatric Musculoskeletal Health, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Yuki Mihara (Y)

Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Tomohiro Yamada (T)

Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Takahiro Natsume (T)

Pharmacology Group, Hamamatsu Pharma Research, Inc., Hamamatsu, Japan.

Shinya Ogawa (S)

Pharmacology Group, Hamamatsu Pharma Research, Inc., Hamamatsu, Japan.

Yuji Awaga (Y)

Pharmacology Group, Hamamatsu Pharma Research, Inc., Hamamatsu, Japan.

Hiroyuki Takamatsu (H)

Pharmacology Group, Hamamatsu Pharma Research, Inc., Hamamatsu, Japan.

Yukihiro Matsuyama (Y)

Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Classifications MeSH