Habituation attenuates the sex-specific associations between ischemic pain, blood pressure, and arterial stiffness in young adults

Zoe R. Lincoln, Wesley T. Blumenburg, Brett L. Cross, Joseph D. Vondrasek, Joseph C. Watso, Andrew A. Flatt, Braxton Linder, Austin T. Robinson, Gregory J. Grosicki

Research output: Contribution to journalArticlepeer-review


Cardiovascular reactivity (CVR) during physical stress is prognostic for incident cardiovascular disease. CVR is influenced by perceived pain. However, there is limited data on the effect of sex differences and repeated exposures to painful stimuli on CVR. We measured blood pressure (BP) and carotid-femoral pulse wave velocity (cf-PWV; an index of arterial stiffness) at rest, during isometric handgrip (HG) exercise at 30% of maximum voluntary contraction, and during postexercise circulatory occlusion (PECO) during two identical trials in 39 adults (20M/19F; 18-39 yr). We assessed participants' perceived pain using a visual analog scale after the first minute of each stimulus. We collected BP during minute 2 of each stimulus and cf-PWV during minute 3 of each stimulus. In male participants, we observed moderate associations (Ps ≤ 0.023) between perceived pain and changes in brachial diastolic (ρ = 0.620) and mean BP (ρ = 0.597); central diastolic, mean, and systolic BP (ρs = 0.519-0.654); and cf-PWV (ρ = 0.680) during PECO in trial 1, but not trial 2 (Ps ≥ 0.162). However, in female participants, there were no associations between pain and CVR indices during either trial (Ps ≥ 0.137). Irrespective of sex, reductions in perceived pain during trial 2 relative to trial 1 were weakly to moderately associated (Ps ≤ 0.038) with reductions in brachial diastolic (ρ = 0.346), mean (ρ = 0.379), and systolic BP (ρ = 0.333); central mean (ρ = 0.400) and systolic BP (ρ = 0.369); and cf-PWV (ρ = 0.526). These findings suggest that 1) there are sex differences in pain modulation of CVR in young adults and 2) habituation blunts pain and CVR during PECO, irrespective of sex.NEW & NOTEWORTHY We demonstrate sex differences in the association between pain perception and cardiovascular reactivity (CVR) during ischemic pain. We also demonstrate habituation to pain and reduced CVR during repeated exposure in a sex-independent manner. Accounting for sex differences and habituation may improve the prognostic utility of CVR.

Original languageEnglish (US)
Pages (from-to)H1323-H1330
JournalAmerican journal of physiology. Heart and circulatory physiology
Issue number6
StatePublished - Dec 1 2022
Externally publishedYes


  • cardiovascular disease
  • cardiovascular reactivity
  • hypertension
  • ischemia
  • sex differences

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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