Mechanistic involvement of noradrenergic neuronal neurotransmitter release in cutaneous vasoconstriction during autonomic dysreflexia in persons with spinal cord injury

Michelle Trbovich, Yubo Wu, Terry Romo, Wouker Koek, Dean Kellogg

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Autonomic dysreflexia (AD) is a potentially life-threatening consequence in high (above T6) spinal cord injury that involves multiple incompletely understood mechanisms. While peripheral arteriolar vasoconstriction, which controls systemic vascular resistance, is documented to be pronounced during AD, the pathophysiological neurovascular junction mechanisms of this vasoconstriction are undefined. One hypothesized mechanism is increased neuronal release of norepinephrine and co-transmitters. We tested this by examining the effects of blockade of pre-synaptic neural release of norepinephrine and co-transmitters on cutaneous vasoconstriction during AD, using a novel non-invasive technique; bretylium (BT) iontophoresis followed by skin blood flow measurements via laser doppler flowmetry (LDF). Methods: Bretylium, a sympathetic neuronal blocking agent (blocks release of norepinephrine and co-transmitters) was applied iontophoretically to the skin of a sensate (arm) and insensate (leg) area in 8 males with motor complete tetraplegia. An nearby untreated site served as control (CON). Cutaneous vascular conductance (CVC) was measured (CVC = LDF/mean arterial pressure) at normotension before AD was elicited by bladder stimulation. The percent drop in CVC values from pre-AD vs. AD was compared among BT and CON sites in sensate and insensate areas. Results: There was a significant effect of treatment but no significant effect of limb/sensation or interaction of limb x treatment on CVC. The percent drop in CVC between BT and CON treated sites was 25.7±1.75 vs. 39.4±0.87, respectively (P = 0.004). Conclusion: Bretylium attenuates, but does not fully abolish vasoconstriction during AD. This suggests release of norepinephrine and cotransmitters from cutaneous sympathetic nerves is involved in cutaneous vasoconstriction during AD.

Original languageEnglish (US)
Article number103154
JournalAutonomic Neuroscience: Basic and Clinical
Volume252
DOIs
StatePublished - Apr 2024

Keywords

  • Autonomic dysreflexia
  • Cutaneous vascular conductance
  • Spinal cord injury

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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