Low-dose morphine reduces pain perception and blood pressure, but not muscle sympathetic outflow, responses during the cold pressor test

s. Joseph C. Watso, Luke N. Belval, Frank A. Cimino, Bonnie D. Orth, Joseph M. Hendrix, Mu Huang, Elias Johnson, Josh Foster, Carmen Hinojosa-Laborde, Craig G. Crandall

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Our knowledge about how low-dose (analgesic) morphine affects autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low-dose morphine affects human autonomic cardiovascular responses during painful stimuli in conscious humans. Therefore, we tested the hypothesis that low-dose morphine reduces perceived pain and subsequent sympathetic and cardiovascular responses in humans during an experimental noxious stimulus. Twenty-nine participants (14 females/15 males; 29 ± 6 yr; 26 ± 4 kg m_2, means ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed a cold pressor test (CPT; hand in ∼0.4°C ice bath for 2 min) before and ∼35 min after drug/placebo administration (5 mg iv morphine or saline). We compared pain perception (100 mm visual analog scale), muscle sympathetic nerve activity (MSNA; microneurography; 14 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) between trials (at both pre- and postdrug/placebo time points) using paired, two-tailed t tests. Before drug/placebo infusion, perceived pain (P = 0.92), DMSNA burst frequency (n = 14, P = 0.21), and Dmean BP (P = 0.39) during the CPT were not different between trials. After the drug/placebo infusion, morphine versus placebo attenuated perceived pain (morphine: 43 ± 20 vs. placebo: 57 ± 24 mm, P < 0.001) and Dmean BP (morphine: 10 ± 7 vs. placebo: 13 ± 8 mmHg, P = 0.003), but not DMSNA burst frequency (morphine: 10 ± 11 vs. placebo: 13 ± 11 bursts min_1, P = 0.12), during the CPT. Reductions in pain perception and Dmean BP were only weakly related (r = 0.34, P = 0.07; postmorphine CPT minus postplacebo CPT). These data provide valuable information regarding how low-dose morphine affects autonomic cardiovascular responses during an experimental painful stimulus.

Original languageEnglish (US)
Pages (from-to)H223-H234
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1
StatePublished - Jul 2022


  • algometry
  • cerebral tissue
  • opioids
  • respiration
  • sympathoexcitatory

ASJC Scopus subject areas

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


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