Mechanisms of Pain Hypersensitivity in a Human Skin Inflammation Model
Status:
COMPLETED
Trial end date:
2025-07-11
Target enrollment:
Participant gender:
Summary
The main goal of this double-blind, randomized, placebo-controlled crossover study is to understand the molecular mechanisms of inflammation-induced increased pain sensitivity (hyperalgesia). These mechanisms are studied using a recently established human model of skin inflammation that mimics aspects of skin infection. A localized inflammatory response in the skin of healthy volunteers is elicited by locally injecting a small, safe dose of Lipopolysaccharide (LPS), a major component of gram-negative bacteria.
The study addresses three key research questions:
* Role of RAGE: To investigate if certain inflammatory effects of LPS, which contribute to hyperalgesia, are mediated by a signaling pathway involving the RAGE receptor.
* Pain Sensitization: To examine how skin inflammation affects pain caused by acidic stimuli, and to differentiate this from purely mechanical pain.
* Role of TRPV1: To determine if the contribution of the TRPV1 ion channel to acid-induced pain is different in inflamed skin.
Participants will undergo an experimental session 4.5 hours after LPS injection to measure skin blood flow (using laser speckle imaging), mechanical pain sensitivity (using specialized tweezers), and pain induced by injecting a solution, of which the pH is gradually decreasing (acid-induced pain).
The study has minimal risks due to the small, safe doses of substances used ('microdosing') and aims to lay the groundwork for developing new treatments for inflammatory pain conditions.