Vecchio Silvia Lo, Finocchietti Sara, Gazerani Parisa, Petersen Lars J, Arendt-Nielsen Lars, Graven-Nielsen Thomas
Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University Aalborg, Denmark.
Department of Clinical Medicine, Imaging and Informatics Center, Aalborg University Aalborg, Denmark ; Department of Nuclear Medicine, Clinical Cancer Research Center, Aalborg University Hospital Aalborg, Denmark.
Int J Physiol Pathophysiol Pharmacol. 2014 Oct 11;6(3):143-52. eCollection 2014.
Experimental models of prolonged pain hypersensitivity in humans are desirable for screening novel analgesic compounds. In this study, heat stimuli were applied in ultraviolet-B (UVB)-irradiated skin and in the UVB-irradiated skin combined with nerve growth factor (NGF)-injected muscle to investigate 1) whether the evoked mechanical hypersensitivity by UVB irradiation would be prolonged or enhanced following heat rekindling, and 2) whether the combination between cutaneous and muscle hypersensitivity may influence the rekindling effects. Skin sensitization was induced in 25 volunteers by UVB irradiation in areas above the upper-trapezius muscle, low-back or forearm. Muscle sensitization was induced in the low back by bilateral injections of NGF. The area of cutaneous hyperalgesia was evaluated 3 days after the irradiation by mechanical pin-prick stimulation whereas the areas of allodynia were evaluated 1, 2 and 3 days after irradiation by von Frey hair assessments. Cutaneous heat stimulation (40°C for 5 min) was performed on the 3(rd) day to investigate its effect on the areas of cutaneous allodynia and hyperalgesia. Findings revealed that 1) allodynia and hyperalgesia developed following UVB irradiation, 2) heat stimulation of the UVB-irradiated skin enlarged both hyperalgesic and allodynic areas (P < 0.01), and 3) muscle sensitization did not influence the effect of UVB on allodynia or the response to heat rekindling. These data suggest that heat rekindling applied to an UVB-sensitized skin can maintain or facilitate allodynia and hyperalgesia for a longer period offering a suitable model for testing analgesic compounds when sufficient duration of time is needed for investigation of drug efficacy.
建立人类长期疼痛超敏反应的实验模型，有助于筛选新型镇痛化合物。本研究通过对紫外线B（UVB）照射的皮肤以及UVB照射皮肤联合注射神经生长因子（NGF）的肌肉施加热刺激，以探究：1）热刺激是否会延长或增强UVB照射诱发的机械性超敏反应；2）皮肤和肌肉超敏反应的联合是否会影响热刺激的效果。对25名志愿者的上斜方肌上方、下背部或前臂区域进行UVB照射，诱导皮肤致敏。通过在双侧下背部注射NGF诱导肌肉致敏。照射3天后，通过机械针刺刺激评估皮肤痛觉过敏区域，而在照射后1、2和3天，通过von Frey毛发评估法评估异常性疼痛区域。在第3天进行皮肤热刺激（40°C，持续5分钟），以研究其对皮肤异常性疼痛和痛觉过敏区域的影响。研究结果显示：1）UVB照射后出现异常性疼痛和痛觉过敏；2）对UVB照射的皮肤进行热刺激会扩大痛觉过敏和异常性疼痛区域（P < 0.01）；3）肌肉致敏不影响UVB对异常性疼痛的作用或热刺激的反应。这些数据表明，对UVB致敏的皮肤施加热刺激可维持或促进异常性疼痛和痛觉过敏更长时间，为在需要足够长的时间来研究药物疗效时测试镇痛化合物提供了合适的模型。
