The purpose of this study are to compare the efficacy of two different commercially available local anesthetics on AFXL pretreated skin and to assess the role of the application time in this technique.

Rationale: In dermatology anesthetics are frequently injected or topically applied to achieve local anesthesia. Injectable anesthetics are effective but uncomfortable during administration, especially for people who are needle phobic. Application of topical anesthesia is painless but time consuming and often only partial aesthesia is achieved due to the barrier function of the stratum corneum. (Manuskiatti, Triwongwaranat et al. 2010) Penetration of local anesthetics could be enhanced by pretreatment of the skin with ablative fractional lasers (AFXL) which locally disrupts the stratum corneum by creating an array of microscopic ablation channels. (Sklar, Burnett et al. 2014) In a previous pilot study, conducted at our institute, we demonstrated that effective anesthesia could be achieved within ten minutes after application of a topical anesthetic on skin pretreated with AFXL at painless settings. (Meesters, Bakker et al. 2015) However, little is still known about the role of the type of anesthetic the type of anesthetic and the application time on the efficacy of the anesthesia.

Objective: The objective of this study is to compare the efficacy of two different commercially available local anesthetics on AFXL pretreated skin, a low concentration articaine solution and a high concentration lidocaine/tetracaine cream. We also aim to compare the efficacy of AFXL assisted topical anesthesia after various different application times.

Study design: Prospective, single blinded, randomized, controlled, within subject, pilot study.

Study population: 15 healthy volunteers ≥18 years, who give written informed consent

Intervention: In each subject, six test regions on subject's back of 1x1 cm will be pretreated with the fractional carbon dioxide (CO2) laser at 2.5 mJ and 15% density and will be randomly allocated to application of (I) articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml 30 solution (AHES) (5 minutes application time), (II) AHES (15 minutes application time), (III) AHES (25 minutes application time), (IV) lidocaine 70 mg/g + tetracaine 70 mg/g cream (LTC) (5 minutes application time, (V) LTC (15 minutes application time), (VI) LTC (25 minutes application time). After 15 minutes a pain stimulus, consisting of a pass with the fractional CO2 laser at 50 mJ and 5% density (scanned area 6x6 mm), will be given at each test region. In addition, a reference pain stimulus with the CO2 laser at the same settings will be given at unanesthetized skin. Subjects will be asked to indicate pain on a visual analogue scale (VAS) from 0-10 (0: no pain; 10: worst imaginable pain) directly after each pain stimulus

Inclusion Criteria:

• Fitzpatrick skin type I or II
• Age ≥18 years
• Patient is willing and able to give written informed consent

Exclusion Criteria:

• History of keloid or hypertrophic scar formation or complicated wound healing
• Presence of any active skin disease
• Known allergy to local anesthesia
• Pregnancy or lactation
• Incompetency to understand what the procedure involves
• Current complaints of chronic pain or other alterations in pain sensation (e.g. due to diabetes mellitus or lepra)
• Current treatment with systemic analgesics or other medication that can influence pain sensation
• Current treatment with anticoagulants
• Fitzpatrick skin type III-VI
• Excessive sun tan