Samuelsson Monika, Leffler Ann-Sofie, Hansson Per
Clinical Pain Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden.
Department of Occupational Therapy, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden.
Scand J Pain. 2011 Apr 1;2(2):85-92. doi: 10.1016/j.sjpain.2011.01.003.
Introduction In order to develop valid experimental human pain models, i.e., models potentially reflecting mechanisms underlying certain expressions of clinical pain conditions, similarities and discrepancies of symptoms/signs must first and foremost be evaluated comparing the two. In a situation where symptoms/signs appear to be similar, a potential pitfall with surrogate models would be that pathophysiological mechanisms in clinical conditions and experimental models might differ, i.e., one symptom/sign may be due to several different mechanisms. Symptoms and signs caused by intradermally injected capsaicin have been suggested to reflect aspects of the clinical phenomenology of neuropathic pain, e.g., dynamic mechanical allodynia. Psychophysical characteristics of brush-evoked pain in the pain area in patients with painful peripheral neuropathy were compared with brush-evoked pain in the secondary hyperalgesic area in capsaicin-treated skin in patients and in healthy subjects using different temporo-spatial stimulus parameters. Method Nine patients were examined in the area of painful neuropathy and subsequently in the corresponding contralateral secondary site, i.e., the secondary hyperalgesic area after an intradermal capsaicin injection. Nine healthy age- and sex-matched subjects were examined in a corresponding area after capsaicin injection. Brush-evoked allodynia was induced by lightly stroking 2 different distances of the skin 2 or 4 times with brushes of 2 different widths. Intensity and duration of brush-evoked allodynia was recorded using a computerized visual analogue scale. The total brush-evoked pain intensity, including aftersensation was calculated as the area under the curve. In addition, similarities and discrepancies in the selection of sensory-discriminative and affective descriptors of the painful experience have been surveyed in the area of neuropathy and in the area of secondary hyperalgesia. Results All patients reported brush-evoked pain in their area of painful neuropathy during all stimuli. Eight out of 9 patients reported brush-evoked pain in an area outside the flare in the capsaicin treated skin and only 3 out of 9 healthy subjects reported brush-evoked pain in an area outside the flare. Within patients there was no significant difference between sides regarding the influence of the various temporo-spatial stimulus parameters on the total brush-evoked pain intensity. Of all parameters tested, only increased number of strokes resulted in significantly higher brush-evoked pain intensity. The most commonly used sensory-discriminative descriptors during brush-evoked pain in the area of painful neuropathy and in the capsaicin-induced secondary hyperalgesic area in patients and controls were smarting and burning and for the affective descriptors troublesome and annoying. Conclusions Similarities were found regarding the influence of temporo-spatial stimulus parameters on brush-evoked allodynia in the capsaicin-induced secondary hyperalgesic area contralateral to the area of painful neuropathy and their influence when testing the area of neuropathic pain. Only 3/9 healthy subjects reported brush-evoked pain after capsaicin injection, a finding that may be related to this group reporting less spontaneous pain than the patients after injection. A hyperexcitable nervous system due to the contralateral clinical condition may also have a bearing on the frequent finding of capsaicin-induced allodynia in the patients (8/9). Implications The low prevalence of tactile allodynia in healthy volunteers makes the capsaicin model an unattractive strategy.
引言 为了开发有效的实验性人类疼痛模型,即可能反映某些临床疼痛状况潜在机制的模型,首先必须评估两者症状/体征的异同。在症状/体征看似相似的情况下,替代模型的一个潜在陷阱是临床状况和实验模型中的病理生理机制可能不同,即一种症状/体征可能由几种不同机制引起。皮内注射辣椒素所引起的症状和体征已被认为可反映神经性疼痛临床现象学的某些方面,例如动态机械性异常性疼痛。使用不同的时空刺激参数,将疼痛性周围神经病变患者疼痛区域内刷擦诱发疼痛的心理物理学特征与辣椒素处理皮肤的患者及健康受试者的继发性痛觉过敏区域内刷擦诱发疼痛的心理物理学特征进行了比较。
方法 对9例患者的疼痛性神经病变区域进行检查,随后在相应的对侧继发部位进行检查,即皮内注射辣椒素后的继发性痛觉过敏区域。对9例年龄和性别匹配的健康受试者在注射辣椒素后的相应区域进行检查。用两种不同宽度的刷子以两种不同的距离轻刷皮肤2次或4次,诱发刷擦诱发的异常性疼痛。使用计算机化视觉模拟量表记录刷擦诱发的异常性疼痛的强度和持续时间。将包括后感觉在内的刷擦诱发疼痛的总强度计算为曲线下面积。此外,还对神经病变区域和继发性痛觉过敏区域中疼痛体验的感觉辨别性和情感性描述词的选择异同进行了调查。
结果 所有患者在所有刺激过程中均报告其疼痛性神经病变区域有刷擦诱发疼痛。9例患者中有8例报告在辣椒素处理皮肤的红晕外区域有刷擦诱发疼痛,而9例健康受试者中只有3例报告在红晕外区域有刷擦诱发疼痛。在患者中,不同时空刺激参数对刷擦诱发疼痛总强度的影响在两侧之间无显著差异。在所有测试参数中,只有刷擦次数增加导致刷擦诱发疼痛强度显著升高。在患者和对照的疼痛性神经病变区域及辣椒素诱发的继发性痛觉过敏区域中,刷擦诱发疼痛时最常用的感觉辨别性描述词是刺痛和灼痛,情感性描述词是麻烦和讨厌。
结论 发现时空刺激参数对辣椒素诱发的继发性痛觉过敏区域(与疼痛性神经病变区域对侧)刷擦诱发的异常性疼痛的影响,与测试神经病变疼痛区域时的影响相似。注射辣椒素后只有3/9的健康受试者报告有刷擦诱发疼痛,这一发现可能与该组报告的自发疼痛比注射后患者少有关。由于对侧临床状况导致的神经系统兴奋性过高也可能与患者中频繁出现辣椒素诱发的异常性疼痛(8/9)有关。
启示 健康志愿者中触觉异常性疼痛的低患病率使得辣椒素模型成为一种缺乏吸引力的策略。