Capsaicin-based analgesic balm attenuates the skeletal muscle metaboreflex in healthy humans

Abstract

The exercise pressor reflex (EPR) is comprised of group III and IV skeletal muscle afferents and is one of the principal mediators of the cardiovascular response to exercise. In animals, capsaicin-based analgesic balm (CAP) attenuates the pressor response to muscle contraction, indicating the transient receptor potential vanilloid 1 (TRPv1) receptor (localized on the group IV afferent neuron) as an important mediator of the EPR. However, whether these findings can be extrapolated to humans remains unknown. Here, we tested the hypothesis that CAP would attenuate blood pressure (BP) and muscle sympathetic nerve activity (MSNA) responses to isolated muscle metaboreflex activation in healthy men. MSNA (microneurography) and beat-to-beat heart hate (HR, by electrocardiography), and BP (finger photoplethysmography) were continuously measured in eight healthy males (23 ± 5 yr) at rest, during isometric handgrip exercise, and during postexercise ischemia (PEI). Trials were performed before and 30 and 60 min after the topical application of CAP (0.1%, CAPZASIN-HP) over the volar forearm of the subject's exercising arm. Isometric exercise evoked increases in mean BP (∆32 ± 4 mmHg) and MSNA (∆26 ± 5 bursts/min; ∆19 ± 5 bursts/100 heart beats). The increases in BP during handgrip were not affected by CAP, but the increase in MSNA was lower after 60 min of CAP application. During PEI, the increases in BP and MSNA were all significantly less than those before CAP (all P < 0.05). In conclusion, CAP attenuated BP and sympathetic responses evoked by PEI in humans. These data provide evidence that transient receptor potential vanilloid 1 receptors potentially contribute to the EPR in humans, via its metabolic component. NEW & NOTEWORTHY We found that topical application of capsaicin-based analgesic balm attenuates arterial blood pressure and muscle sympathetic nerve activity during isolated muscle metaboreflex activation following isometric handgrip exercise in healthy humans. These findings suggest that the transient receptor potential vanilloid 1 may contribute to the exercise pressor reflex in humans via its metabolic component.

GABAA receptors modulate sympathetic vasomotor outflow and the pressor response to skeletal muscle metaboreflex activation in humans

“…PEI partially maintains exercise‐induced increases in MSNA and arterial BP, whereas HR tends to return toward baseline, indicating that metaboreflex activation has a minimal effect on HR (Alam & Smirk, ; Vianna et al . ; Teixeira et al . ).…”

“…Sympathetic bursts in the integrated neurogram were identified using custom‐built automated analysis software (Hamner & Taylor, ; Vianna et al . ); burst identification was then corrected via visual inspection by a single observer (LCV). MSNA was quantified as burst incidence (bursts 100 heart beats –1 ) and burst frequency (bursts min –1 ).…”

“…Multiunit recordings of postganglionic MSNA were obtained as described previously (Fisher et al 2015a;Fernandes et al 2018;Vianna et al 2018;Mansur et al 2019). Briefly, a unipolar tungsten microelectrode was inserted percutaneously through the intact skin and positioned into muscle nerve fascicles of the peroneal nerve of the right leg at the fibular head, and a reference electrode was placed s.c. 2-3 cm distal.…”

“…Neural activity was amplified (gain 20,000) and filtered (band pass 0.3-0.5 kHz) with an isolated amplifier and headstage (NeuroAmp EX, AD Instruments). Sympathetic bursts in the integrated neurogram were identified using custom-built automated analysis software (Hamner & Taylor, 2001;Vianna et al 2018); burst identification was then corrected via visual inspection by a single observer (LCV). MSNA was quantified as burst incidence (bursts 100 heart beats -1 ) and burst frequency (bursts min -1 ).…”

“…These neural signals converge into the nucleus of the tractus solitarius (NTS) in the medulla oblongata, a major centre for autonomic integration in the brain stem (Potts, 2006). Notably, although all three neural mechanisms are relevant to cardiovascular regulation during exercise, considerable attention has been given to the EPR as a result of its importance in determining the magnitude of sympathoexcitation during muscle effort (Kaufman & Hayes, 2002;Smith et al 2006;Kaufman, 2012;Michelini et al 2015;Vianna et al 2018).…”