3. Discussion
skin pain, dermal pain, Pain, pain
EVENTS, BLOOD
Sweating-induced dermal pain is triggered by daily events, such as bathing, exercise, and mental stress.Bradykinin is an endogenous substance that causes pain.This study is a crossover, single-blind, placebo-controlled, randomized comparative study. Due to the rarity of patients with sweating-induced dermal pain, the number of patients capable to be enrolled in the study is limited. Moreover, the subjective nature of pain perception makes it difficult to compare pain levels across patients. To minimize these limitations, a crossover design is employed. Furthermore, to account for the potential placebo effect on dermal pain due to expectations of drug efficacy, the present study is designed as a single-blinded, placebo-controlled, randomized study.The icatibant dose setting is based on its efficacy and safety. A pharmacodynamic analysis estimated the tolerated dosage needed to reduce bradykinin-induced reactions to be 0.4 mg/kg,The primary endpoint is to assess the effectiveness of icatibant in treating sweating-induced dermal pain. Pain will be evaluated using a VAS score by inducing dermal pain with a thermal load before and after icatibant administration. This approach has been chosen due to the importance of evaluating pain in patients with the dermal pain and the subjective nature of pain perception. To induce dermal pain, both lower legs will be placed in warm water (~43°C) for 30 minutes.Blood histamine and ACE levels will be measured as biomarkers. Similar to bradykinin, histamine causes skin pain and may be associated with dermal pain.A limitation of this study is that a small number of patients are planned to be enrolled. Since this preliminary study is conducted for proof of concept, only ten patients will participate to explore the effect of blocking kinin-bradykinin pathway to sweating-induced dermal pain. Moreover, the efficacy of icatibant in this study does not necessarily imply that the use of icatibant is a practical treatment for the pain due to its short effective duration of action. According to pharmacodynamic analysis, icatibant exerts its effectiveness for only 5.5 to 6 hours.Overall, this study contributes to a better understanding of the underlying mechanisms of sweating-induced dermal pain and has the potential to improve the quality of life for patients experiencing this debilitating condition by suggesting potential treatment options.