Does sympathetic nerve stimulation cause flushing?

Sympathetic Nerve Stimulation and Flushing

No, sympathetic nerve stimulation typically causes vasoconstriction rather than flushing, while it is the inhibition of sympathetic activity or activation of parasympathetic pathways that can lead to facial flushing.

Physiological Mechanisms of Flushing

Flushing occurs primarily through two main mechanisms:

1. Vasodilation mechanisms:

   • Inhibition of sympathetic vasoconstrictor tone
   • Direct parasympathetic stimulation
   • Release of vasoactive substances (substance P, calcitonin gene-related peptide, histamine)

2. Nerve axon reflex pathway:

   • Stimulation of nociceptive C-fibers leads to antidromic stimulation of adjacent C-fibers
   • These fibers release vasoactive substances including substance P, calcitonin gene-related peptide (CGRP), and histamine
   • These substances cause vasodilation and increased blood flow 1

Sympathetic Stimulation Effects on Vasculature

Sympathetic nerve stimulation has several important effects:

• Causes vasoconstriction through alpha-adrenergic mechanisms 2
• Reduces endothelium-dependent, flow-mediated vasodilation 2
• Increases vascular resistance in both large and small vessels 3
• Promotes vascular hypertrophy during chronic stimulation 4

Clinical Evidence Against Sympathetic-Induced Flushing

Several clinical conditions and treatments demonstrate the relationship between sympathetic activity and flushing:

1. Baroreceptor activation therapy:

   • Activates baroreceptors to reduce sympathetic activity
   • Results in arterial dilation and improved renal blood flow 1
   • Used experimentally in resistant hypertension

2. Beta-blockers for flushing:

   • Effective for managing facial flushing in rosacea 5
   • Work by blocking sympathetic effects, supporting that sympathetic activation is not the cause of flushing

3. Malignant hyperthermia:

   • Features include increased sympathetic nervous system outflow
   • Exposed skin may become hot, flushed and sweaty due to metabolic effects rather than direct sympathetic stimulation 1

Conditions Where Flushing Occurs

Flushing is commonly seen in:

• Rosacea (associated with vasodilation and inflammation)
• Medication reactions (niacin, calcium channel blockers)
• Carcinoid syndrome
• Mastocytosis
• Anaphylaxis
• Menopause (hot flashes)

Autonomic Pathways and Flushing

The relationship between autonomic pathways and flushing is complex:

• Parasympathetic activation → vasodilation → potential flushing
• Sympathetic inhibition → reduced vasoconstriction → potential flushing
• Sympathetic activation → vasoconstriction → typically prevents flushing

Clinical Applications

Understanding these mechanisms has important clinical implications:

• Beta-blockers can be effective for treating facial flushing by reducing sympathetic-mediated vasodilation 5
• Alpha-adrenergic blockade can reverse sympathetic vasoconstriction, potentially worsening flushing 2
• Endothelial dysfunction in heart failure contributes to abnormal vasodilatory responses during exercise 1

In summary, sympathetic nerve stimulation typically promotes vasoconstriction rather than vasodilation, making it an unlikely direct cause of flushing. Flushing is more commonly associated with parasympathetic activation, sympathetic inhibition, or direct effects of vasoactive substances on blood vessels.