Sensory and sympathetic nerve contributions to the cutaneous vasodilator response from a noxious heat stimulus

Abstract

We investigated the roles of sensory and noradrenergic sympathetic nerves on the cutaneous vasodilator response to a localized noxious heating stimulus. In two separate studies, four forearm skin sites were instrumented with microdialysis fibres, local heaters and laser-Doppler probes. Skin sites were locally heated from 33 to 42• C or rapidly to 44 • C (noxious). In the first study, we tested sensory nerve involvement using EMLA cream. Treatments were as follows: (1) control 42• C; (2) EMLA 42 • C; (3) control 44 • C; and (4) EMLA 44• C. At the EMLA-treated sites, the axon reflex was reduced compared with the control sites during heating to 42• C (P < 0.05). There were no differences during the plateau phase (P > 0.05). At both the sites heated to 44• C, the initial peak and nadir became indistinguishable, and the EMLA-treated sites were lower compared with the control sites during the plateau phase (P < 0.05). In the second study, we tested the involvement of noradrenergic sympathetic nerves in response to the noxious heating using bretylium tosylate (BT). Treatments were as follows: (1) • C sites, there was no apparent initial peak or nadir, but the plateau phase was reduced at the BT-treated sites (P < 0.05). These data suggest that both sympathetic nerves and sensory nerves are involved during the vasodilator response to a noxious heat stimulus.

The contribution of sensory nerves to cutaneous vasodilatation of the forearm and leg to local skin heating

“…One site on the forearm and one site on the leg were randomly chosen to receive the topical EMLA cream treatment (AstraZeneca, Wilmington DE, USA; 2.5 % lidocaine and 2.5 % prilocaine). As per our previous experiments blocking cutaneous sensory function with EMLA cream (Tew et al 2011a;Carter and Hodges 2011;Hodges et al 2007Hodges et al , 2009), approximately 2.5 g of the EMLA cream was applied on the forearm to an area of the skin roughly equal to 4 cm 2 . An occlusive dressing (Tegaderm, 3 M, London, ON, Canada) was placed over the applied EMLA cream and left for 1 h. The EMLA cream was then wiped clear and a second application was applied for an additional hour.…”

“…During this time the second EMLA application was applied on the leg. Finally, T loc on the forearm sites was increased to 44 °C at 1 °C min −1 (2 min in total) and held at this temperature for 20 min to achieve maximal vasodilatation (Tew et al 2011a;Carter and Hodges 2011;Vionnet et al 2014;Lawley et al 2014). After this, forearm data collection sensory nerve blockade was again verified.…”

“…Following the second 1 h application of EMLA on the forearm, the first EMLA application was applied to the leg and was left for an hour under occlusive dressing. After the second 1 h application of EMLA was removed from the forearm, sensory nerve blockade over the area of interest was verified by alternating between brushing, pricking, and pinching with a set of pointed tweezers (Tew et al 2011a;Hodges et al 2007;Lorenzo and Minson 2007;Minson et al 2001;Carter and Hodges 2011). The EMLA treatments and durations for the arm and the leg were the same for all participants.…”

“…The initial vasodilatory response, at least in the forearm, is thought to be primarily mediated by both sympathetic and sensory nerves (Minson et al 2001(Minson et al , 2002Tew et al 2011a;Carter and Hodges 2011), with transient receptor potential vanilloid (TRPV) type 1 ion channels (Wong and Fieger 2010) located on sensory afferent nerves. Additionally, these studies have reported that sensory nerves do not appear to be involved in the secondary sustained vasodilatation during prolonged local skin heating.…”

Model-based quantitative assessment of skin microcirculatory blood flow and oxygen saturation

“…Kellogg et al [129] showed that even a small sense of pain caused the vasodilation to remain even in the presence of nitric oxide synthase inhibitors, indicating other involving mechanisms. Carter and Hodges [130] reported an absence of initial peak and nadir when heating the skin rapidly to 44°C, where all subjects reported a short period of mild pain. Even if none of the participants in the studies in paper IV and V reported a sense of pain, a first peak and nadir were absent in several subjects in paper V. This indicates that the chosen temperature of 44°C in the study had probably caused minor pain and a temperature of <41°C is probably a better choice in future studies.…”