Davis Karen D, Meyer Richard A, Turnquist Jennifer L, Filloon Tom G, Pappagallo Marco, Campbell James N
Department of Neurosurgery, The Johns Hopkins University, Baltimore, MD 21205 USA The Applied Physics Laboratory, The Johns Hopkins University, Baltimore, MD 21205 USA The Procter and Gamble Company, Cincinnati, OH, USA.
Pain. 1995 Apr;61(1):17-26. doi: 10.1016/0304-3959(94)00154-7.
Intradermal injection of the capsaicin analogue, NE-21610 (Procter and Gamble), inactivates nociceptors but not low-threshold mechanoreceptors in monkey. The present study examined the effects of cutaneous NE-21610 on heat and mechanical sensation in normal human volunteers. In the first series of experiments, subjects received intradermal (i.d.) injections (30 microliters) of the vehicle alone or with the drug (0.3, 3.0, 10 micrograms) into different sites on the volar forearm. Subjects were randomly assigned to 1 of 3 protocols to examine drug-evoked pain (n = 8), or alterations in pain to heat (n = 8) or mechanical (n = 8) stimuli induced by the drug. An additional 7 subjects rated pain to mechanical and heat stimuli before and after subcutaneous (s.c.) injections (300 microliters) of the vehicle or drug (100 micrograms). The peak pain occurred at the time of injection, was of short duration, and was similar for vehicle and drug injections. A mild, dose-related pain followed that lasted up to 2 h. Von Frey thresholds for detection, sharpness, and pain at the injection site (measured 24 h after injection) were not significantly altered by either i.d. or s.c. drug administration. However, pain to stepped heat stimuli was reduced in a dose-dependent fashion for both types of injection. At the highest drug doses, analgesia to heat stimuli was still present 1 week after injection. Recovery of heat sensitivity occurred several weeks after injection. This dissociated loss of heat but not mechanical pain sensibility may be due to: (1) a selective action of the drug on heat transducers in nociceptors responsive to both heat and mechanical stimuli, or (2) a selective action on that subset of nociceptors responsible for signaling heat-evoked pain.
在猴子体内，皮内注射辣椒素类似物NE-21610（宝洁公司）可使伤害性感受器失活，但不会使低阈值机械感受器失活。本研究检测了皮肤注射NE-21610对正常人类志愿者热觉和机械感觉的影响。在第一组实验中，受试者在掌侧前臂的不同部位接受皮内（i.d.）注射（30微升）单独的赋形剂或与药物（0.3、3.0、10微克）混合的溶液。受试者被随机分配到3种方案中的1种，以检测药物诱发的疼痛（n = 8），或药物诱导的热痛（n = 8）或机械痛（n = 8）改变。另外7名受试者在皮下（s.c.）注射（300微升）赋形剂或药物（100微克）前后对机械和热刺激的疼痛进行评分。注射时出现疼痛峰值，持续时间短，赋形剂和药物注射的疼痛相似。随后会出现轻度的、与剂量相关的疼痛，持续长达2小时。注射部位（注射后24小时测量）的von Frey检测阈值、锐度和疼痛程度，无论是皮内还是皮下给药均无明显改变。然而，两种注射方式下，对阶梯式热刺激的疼痛均呈剂量依赖性降低。在最高药物剂量下，注射1周后对热刺激的镇痛作用仍然存在。热敏感性在注射数周后恢复。这种热痛觉而非机械痛觉的分离性丧失可能是由于：（1）药物对伤害性感受器中对热和机械刺激均有反应的热感受器的选择性作用，或（2）对负责传递热诱发疼痛信号的那部分伤害性感受器的选择性作用。
