Distinct BOLD fMRI responses of capsaicin-induced thermal sensation reveal pain-related brain activation in nonhuman primates

Background: Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored. Methodology: Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8). BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle) at baseline and 30 min post-capsaicin (0.1 mg, t...研究背景：约20%的成年人群罹患慢性疼痛，且现有疗法无法实现充分治疗，凸显了开发更优治疗方案的迫切需求。为研发高效镇痛药物，标准化的人类与动物疼痛实验模型至关重要。局部或皮内给药的辣椒素可诱导机体对热、触觉刺激产生痛觉超敏与异痛症，该效应可模拟慢性疼痛状态，是连接临床前研究与临床探索的有效转化模型。诸多疼痛相关行为学与自我报告研究已采用辣椒素疼痛模型，但非人灵长类中辣椒素增强伤害性感受反应的客观生物标志物关联仍有待探索。研究方法：本研究以8只食蟹猴为实验对象，建立了基于非伤害性热刺激的辣椒素诱导性厌恶样功能磁共振成像（fMRI）模型。我们在基线状态与辣椒素（0.1 mg, t……）给药后30分钟两个时间点，采集热刺激范式下的血氧水平依赖性功能磁共振成像（BOLD fMRI）数据：热刺激开启阶段为20秒/42℃，关闭阶段为40秒/35℃，循环4次。