Spine Surgery and Related Research
Online ISSN : 2432-261X
ISSN-L : 2432-261X
Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study
Hiroki UshirozakoGo YoshidaDaisuke TogawaTakao OmuraTomohiko HasegawaYu YamatoTomohiro BannoHideyuki ArimaShin OeYuki MiharaTomohiro YamadaTakahiro NatsumeShinya OgawaYuji AwagaHiroyuki TakamatsuYukihiro Matsuyama
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2019 Volume 3 Issue 4 Pages 368-376


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 Macaca fasciculata using a pressure algometer. The nucleus pulpous of the IVD between L4 and L5 was aspirated and chymopapain (1 mg/mL) was injected under fluoroscopic guidance (n = 2). In two macaques, the nucleus pulpous was only aspirated. Brain activation in response to pressure applied to the lower back was assessed using a 3.0T magnetic resonance imaging scanner in four macaques before and 1, 3, 9, and 14 days after treatment.

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.

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

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