An investigation using capsaicin to examine age-specific skin blood flow responses to local heating
Open Access
- Author:
- Munce, Thayne A
- Graduate Program:
- Kinesiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 03, 2002
- Committee Members:
- Steven Howard Zarit, Committee Member
James Anthony Pawelczyk, Committee Member
Joseph G Cannon, Committee Member
William Lawrence Kenney Jr., Committee Chair/Co-Chair
Kathryn A Bonnett, Committee Member - Keywords:
- cutaneous vasodilation
laser Doppler imaging
neurogenic vasodilation
sensory nerves - Abstract:
- Regulation of skin blood flow (SkBF) is important for both thermoregulatory and inflammatory responses in the human body. SkBF is controlled by a complex interaction of several local and neural mechanisms. Because local SkBF responses can be modified by vasoactive neurotransmitters released from sensory nerves, changes in sensory nerve function in aged skin may contribute to alterations in local thermoregulatory and inflammatory SkBF responses in older individuals. Capsaicin (CPZ) acutely stimulates and chronically desensitizes a specific population of capsaicin-sensitive primary afferent (CSPA) sensory nerves in the skin, making it a useful pharmacological tool for investigating their function. The purpose of this study was to examine age-specific CSPA function and determine the involvement of these nerves in the SkBF response to local heating of the skin. Nine young (18–30 yr), eight middle-aged (40–55 yr) and nine older (65–80 yr) healthy men participated in the experiments. The first part of the study provided an assessment of sensory nerve function in the skin by examining the neurogenic vasodilation caused by CSPA stimulation with acute capsaicin. Eight treatment patches of varying CPZ concentration (Vehicle, 0.001%-10.0% CPZ) were applied to randomized sites on the ventral forearms of the subjects and SkBF was measured after 32 min. The second part of the study consisted of two separate local heating protocols: 1) rapid heating in which local skin temperature (T<sub>loc</sub>) was raised from 33oC to 40oC over ~2 min and maintained at that Tloc for an additional 50 min and 2) a slow heating protocol in which Tloc was increased in a step-wise manner from 35oC to 42oC at a rate of 1oC/5 min and clamped at 42oC for an additional 30 min. Both heating protocols were performed on control and CPZ pretreatment days, separated by one week of repeated topical capsaicin (RTC) applications. RTC pretreatments were used to desensitize CSPAs in the skin so that their role in the SkBF response to local heating could be evaluated by comparing SkBF before and after desensitization. SkBF was measured with a laser Doppler imager (LDI), utilizing multiple scans for the acute capsaicin and slow heating experiments, and a continuous single-point measurement for the rapid heating experiments. Results were expressed as % of maximal cutaneous vascular conductance (%CVCmax) and % of area that was vasodilated (%AVD). There was a significant (P < 0.001) age-specific difference in the CVC response to acute CPZ treatment. In the older group, %CVCmax was less than half of that measured for the younger group at all concentrations of CPZ, with the most significant reduction (32.4 ± 6.5 vs. 79.8 ± 9.0 %CVCmax, P < 0.001) occurring at the 10.0% CPZ site. This attenuated CVC in the older group was due to both a decreased %AVD (P < 0.001) and a decreased CVC within the area that was vasodilated (P < 0.001). RTC caused a significant reduction in CVC compared to the control day in both the middle-aged and older groups (P < 0.05) during the slow heating protocol. The decrease in SkBF in the middle-aged group was due to a reduced %AVD (P < 0.05), while in the older group, decreases in both %AVD and CVC within the vasodilated area (P < 0.05) were responsible for the attenuated response. For the rapid heating protocol, RTC significantly reduced (53.9 ± 4.4 vs. 74.4 ± 7.4 %CVCmax, P < 0.05) the initial sensory nerve-mediated rise in SkBF only in the young group. The attenuated neurogenic vasodilation due to acute capsaicin stimulation in older individuals suggests a reduced sensory nerve function in aged skin. These results also indicate that CSPA activity contributes modestly to the overall SkBF response to local heating of the skin in an age- and temperature-specific manner. Thus, capsaicin desensitization causes reductions in SkBF during local heating that is dependent upon the age-specific contribution of CPSAs to the overall response. These findings suggest that there are age-specific differences in the ability of sensory nerves to modify local thermoregulatory and inflammatory SkBF responses in human skin.