The evaluation of hyaluronic acid, with and without lidocaine, in the filling of nasolabial folds as measured by ultrastructural changes and pain management

J Drugs Dermatol. 2013 Mar;12(3):e46-52.


Background: Pain management is an important objective in procedures involving dermal fillers composed of hyaluronic acid (HA).

Objective: To compare the 1-year clinical results of filling the nasolabial fold with 2 types of filler: large-gel particle HA and large-gel particle HA plus 0.3% lidocaine (HA+L). We compared the level of pain during treatment and 10 minutes after treatment and assessed the safety and efficacy profile, satisfaction, and histological findings (using reflectance confocal microscopy [RCM]).

Materials and methods: We performed a comparative, parallel-group, double-blind trial with an external observer (blinded to the type of treatment administered). The filler was applied to the nasolabial fold in 119 patients (HA in 62 patients and HA+L in 57). Patients were followed at months 3, 9, and 12. Pain was evaluated using a visual analog scale. Efficacy and satisfaction were evaluated using the Wrinkle Severity Rating Scale and the Global Aesthetic Improvement Scale. RCM images (n=32) were taken at baseline and at months 3 and 12.

Results: Pain: The severity of pain was decreased in patients treated with HA+L on application (P <.001) and 10 minutes later ( P=.008). Efficacy and satisfaction: No significant differences existed between the 2 groups at months 3, 9, and 12. RCM: Skin rejuvenation occurred with a 32% increase in the height of the dermoepidermal junction at month 12 (P <.001), which was similar in both groups. Adverse events: At month 3, the most common adverse events (AEs) were erythema (68%) and hematoma (11%). No AEs were recorded at months 9 or 12.

Conclusion: The use of HA+L provides pain relief without affecting efficacy, satisfaction, safety, or the duration of results. RCM showed that the changes in the dermoepidermal junction represented a histological improvement in the skin with similar results in both groups.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / adverse effects
  • Cosmetic Techniques* / adverse effects
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Gels
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Hyaluronic Acid / adverse effects
  • Lidocaine / administration & dosage*
  • Lidocaine / adverse effects
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Nasolabial Fold
  • Pain / drug therapy*
  • Pain / etiology
  • Pain Measurement
  • Patient Satisfaction
  • Rejuvenation
  • Severity of Illness Index
  • Skin Aging
  • Time Factors


  • Anesthetics, Local
  • Gels
  • Hyaluronic Acid
  • Lidocaine