Divergent Muscle Sympathetic Nerve Activity during Cold Pressor Test and Perceived Pain

Abstract

The cold pressor test (CPT) is often used as a noxious stimulus to induce pain, and results in robust and reproducible increases in blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) in humans. In contrast to the relative consistency of CPT, some laboratory techniques (e.g. mental stress) result in divergent MSNA responses, where some individuals exhibit an early‐onset increase in MSNA (i.e. positive responders) and others an early‐onset decrease (i.e. negative responders). The purpose of the present study was to compare perceived pain in subjects based upon their early‐onset MSNA responsiveness (i.e., positive vs. negative) during the CPT. Forty‐three young, healthy adults (21±1yrs; 20 men and 23 women) participated in an experimental visit where continuous BP (finger plethysmography) and MSNA (microneurography) were measured during a 3–5 minute baseline and 2 minute CPT. Perceived pain was recorded in 15 second intervals during CPT using a standard pain scale. The initial 15 seconds of CPT were used to categorize subjects for analysis based on MSNA responsiveness (burst/min), which resulted in the following two groups: 1) positive responders (n=17; 8 women; mean, Δ8 ± 8 burst/min; range Δ0 – 31 burst/min), 2) negative responders (n=26; 15 women; mean, Δ‐4±4 burst/min; range Δ‐14 – 0 burst/min). Reactivity and blood pressure data were analyzed using a mixed ANOVA with time as a within subjects factor and group as a between subjects factor. Independent‐samples t‐tests were used to analyze changes in perceived pain (p<0.05). While there was a significant time×group interaction for MSNA reactivity patterns when expressed as burst frequency (p=0.031) and bursts per 100 heart beats (p=0.043), all groups demonstrated similar systolic (time×group, p=0.888) and diastolic (time×group, p=0.753) blood pressure responsiveness. Heart rate reactivity was also similar between groups (time×group, p=0.777). In contrast to the hemodynamic responses, change of pain during CPT was augmented in responders (8.5±0.4 a.u.) compared to non‐responders (7.4±0.6 a.u.; p=0.007). This was also observed when pain was expressed as a peak change (responders, 10.6 ± 0.4 a.u., non‐responders, 9.2 ± 0.7 a.u.; p=0.011). In summary, our findings suggest a potential relationship between the early‐onset divergence of MSNA reactivity and the changes in perceived pain during the CPT.Support or Funding InformationFunded by the National Institutes of Health (R01 AA‐024892‐01‐A1, R15 HL098676, R15 HL‐122919) and the Portage Health Foundation.