Associations Between Pain Perception, Sympathetic, and Blood Pressure Responses During the Cold Pressor Test

Individuals exhibit varying responses in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) during the pain-inducing cold pressor test (CPT). It is thought that pain, MSNA, and BP responses during the CPT are closely associated. However, limited data support this claim. Therefore, we performed a retrospective analysis to determine the link between pain, MSNA, and BP responses during the CPT. Purpose: We hypothesized that MSNA would mediate the association between pain perception and BP responses during the CPT. Methods: Participants completed a 5-minute baseline and 2-minute CPT (hand in 0.35±0.05°C ice bath) on one (n=21) or two (n=24 tested ≥48 hours apart) occasions. Pain perception was assessed using a 10 cm visual analog scale with anchors [0 cm] “no pain” and [10 cm] “worst imaginable pain.” We measured MSNA via radial microneurography and beat-to-beat BP via finger photoplethysmography during baseline and the CPT. We quantified MSNA as burst frequency (MSNA-BF) and total activity (MSNA-TA; MSNA-BF x burst area). We performed mediation and Spearman rank correlation (ρ) analyses using the pain rating and changes (Δ; CPT minute 2 minus baseline) in MSNA and BP using all 69 visits. We report data as mean±SD or median[IQR]. Results: The participants (n=45, age=29±6 yrs; BMI=26±3 kg/m 2 ; resting MSNA-BF=11[11] bursts/min) were free from overt disease and not taking pain-modifying medications. Across visits, CPT pain was 7.1[2.6] cm, ΔMSNA-BF was 15[16] bursts/min, ΔMSNA-TA was 318[395] % of baseline, and Δmean BP was 17±9 mmHg. The direct, indirect, and total path from pain to Δmean BP were not significant with ΔMSNA-BF as a mediator (estimate≤0.04, p≥0.21). For path estimates, pain to ΔMSNA-BF (estimate: 0.13, p=0.04) was significant, but ΔMSNA-BF to Δmean BP (estimate: 0.16, p=0.11) and pain to Δmean BP (estimate: 0.02, p=0.68) were not. The direct, indirect, and total path from pain to Δmean BP were not significant with ΔMSNA-TA as a mediator (estimate≤0.04, p≥0.38). Pain to ΔMSNA-TA (estimate: 3.58, p=0.22) and ΔMSNA-TA to Δmean BP (estimate: 0.003, p=0.22) were not significant. Between all visits, we found weak correlations between ΔMSNA-BF and Δmean BP (ρ=0.28, p=0.02) as well as ΔMSNA-TA and Δmean BP (ρ=0.26, p=0.04). However, we did not find significant correlations for pain and ΔMSNA-BF (ρ=0.18, p=0.13), pain and ΔMSNA-TA (ρ=0.15, p=0.22), or pain and Δmean BP (ρ=0.03, p=0.81). Conclusion: These data indicate that pain perception may be weakly associated with ΔMSNA-BF and that different ΔMSNA indices may be weakly associated with Δmean BP during the CPT. Thus, the influence of pain on MSNA and BP responses during the CPT could be subtle and influenced by factors not included in our analysis. Nevertheless, these results suggest that the close associations between pain, MSNA, and BP responses during the CPT are not as strong or straightforward as commonly stated. Future studies could further develop our understanding of the interactions of pain perception, the sympathetic nervous system, and blood pressure control. FUNDING: NIH F32HL154565 to LNB. U.S. Army W81XWH-18-2-0012 to CGC. APS Postdoctoral Fellowship, NIH F32HL154559, NIH K01HL160772, & AHA 23CDA1037938 to JCW. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.