著者

後迫 宏紀 吉田 剛 長谷川 智彦 大和 雄 夏目 貴弘 小川 真弥 阿波賀 祐治 Hama Aldric 髙松 宏幸 松山 幸弘

出版者

日本疼痛学会

雑誌

PAIN RESEARCH (ISSN:09158588)

巻号頁・発行日

vol.35, no.1, pp.45-51, 2020-03-31 (Released:2020-05-06)

参考文献数

15

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Functional magnetic resonance imaging (fMRI) is expected as a biomarker of pain because it can objectively evaluate changes in cerebral blood flow associated with neuron activity against pain. We have developed pain models for cynomolgus macaques because it is more compatible with humans in regard to the structures and functions of brain regions which is suggested to be involved in pain in humans. Aside from humans, the cynomolgus macaques are the most widespread primate genus, ranging from Japan to North Africa. Since the macaques are the animal species closest to humans among those which can be used for invasive experiments, they are widely used to understand the mechanisms of the human brain. The purpose of this study is to elucidate pain–related brain activation regions in the macaque models using fMRI. Generally, pain testing in animal models has been based on avoidance behavior against pain stimuli. However, we identified pain–related brain activation regions using fMRI under propofol anesthesia as a more objective evaluation method. In the macaque model of chymopapain–induced discogenic low back pain, the activity of the insular cortex occurred in response to lumbar compression stimulation. In the macaque model of oxaliplatin–induced neuropathic cold hypersensitivity, activation of the insular cortex also occurred in response to cold stimuli. As a result of evaluating pregabalin, duloxetine and tramadol, only duloxetine showed behavioral effectiveness and suppressed activation of the insular cortex due to oxaliplatin–induced neuropathic pain. In the macaque model of postoperative pain, activation of the insula cortex was mainly activated by pressure stimulation. As a result of evaluating morphine, pregabalin and diclofenac, only morphine showed behavioral effectiveness and suppressed activa­tion of the insular cortex due to postoperative pain. However, macaques with naturally occurring endometriosis exhibited a pain response against pressure stimuli to the abdomen, and had activation of the thalamus. As a result of evaluating morphine, meloxicam and acetaminophen, only morphine showed behavioral effectiveness and suppressed activation of thalamus due to abdominal pain from endometriosis. It was suggested that the brain activation regions could change due to various conditions that can cause the pain, as the acute pain increased activation in the insula cortex and the chronic pain increased activation in the thalamus. This study demonstrated the usefulness of fMRI as a pain biomarker, and fMRI analysis using the macaques might provide an advantage for the translation of the findings to human patients. Therefore, these study will contribute to the development of new analgesics for each pain as well as to the progress in the areas of brain research.