Intravenous adenosine activates diffuse nociceptive inhibitory controls in humans

Area of Science:

• Neuroscience
• Pain Research
• Human Physiology

Background:

• Pain can be reduced by other stimuli, a phenomenon known as counterirritation.
• Animal studies suggest this involves diffuse noxious inhibitory controls (DNICs) triggered by C and Aδ fibers.
• In humans, counterirritation is typically induced by noxious stimuli, but the role of C-fibers remains unclear.

Purpose of the Study:

• To investigate if stimulating C-fibers with adenosine triggers DNICs in humans.
• To determine if adenosine induces counterirritation by activating pulmonary C-fibers.
• To explore the potential of C-fiber stimulation in human pain modulation.

Main Methods:

• A double-blind, randomized, cross-over study involving 9 healthy volunteers.
• Intravenous adenosine (140 μg·kg(-1)·min(-1) for 5 min) or placebo was administered.
• Pain perception was assessed via the RIII component of the nociceptive flexor reflex, alongside measurements of dyspnea and ventilatory variables.

Main Results:

• Adenosine administration induced dyspnea, hyperpnea, and tachycardia.
• A significant inhibition of the RIII reflex (24 ± 8%) was observed, indicating counterirritation.
• The temporal patterns of dyspnea and RIII inhibition differed, suggesting complex C-fiber involvement.

Conclusions:

• Intravenous adenosine effectively induces counterirritation in humans, supporting the hypothesis that C-fiber stimulation triggers DNICs.
• The findings suggest that C-fiber activation can modulate pain perception in humans.
• The temporal dissociation observed implies that C-fibers beyond the pulmonary system may contribute to these effects.