Research DOI: 10.1093/asj/sjz113 www.aestheticsurgeryjournal.com © 2019 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals. permissions@oup.com Aesthetic Surgery Journal 2019, Vol 39(10) 1139–1145 Investigation of the Development of Hypersensitivity and Hyperalgesia After Repeated Application of Platelet-Rich Plasma in Rats: An Experimental Study Bilsev Ince, MD ; Mehmet Emin Cem Yıldırım, MD ; Ibrahim Kilinc, MD; Pembe Oltulu, MD; and Mehmet Dadaci, MD Abstract Background: Hyperalgesia, defined as hypersensitivity to pain, refers to sensitization of nociceptors to normal levels of pain. Objectives: We aimed to determine whether hyperalgesia occurs due to the development of sensitization following repeated applications of platelet- rich plasma (PRP), and to ascertain the mechanism responsible for inducing hyperalgesia. Methods: This study, performed between 2016 and 2017, involved 32 rats. A 2 cm × 2 cm area was shaved on the back of 10 experimental and 10 sham control animals. In the experimental animals this area was divided into 4 equal squares of 1 cm × 1 cm, and these squares were numbered 1 (no treatment; only the needle was inserted), 2 (0.2 mL, saline), 3 (0.2 mL, nonactivated PRP), and 4 (0.2 mL, activated PRP). The response of the animals to painful stimuli in these areas was investigated with Von Frey filaments, immediately before application and 4 weeks after the last application. Skin biopsies were taken, and growth factors were evaluated pathologically and biochemically. Results: Hyperalgesia developed in all 4 areas of each experimental rat but not in the sham group. However, areas 3 and 4 had smaller Von Frey g values than areas 1 and 2. When growth hormones were assessed histopathologically and biochemically, nerve growth factor (NGF) levels were found to be higher in areas 3 and 4 than in areas 1 and 2 and the sham group. Conclusions: Both nonactivated and activated PRP resulted in greater hypersensitivity than saline and sham treatment. Development of hyperalgesia may be associated with an increase in NGF as well as increased inflammatory mediators. Editorial Decision date: February 15, 2019; online publish-ahead-of-print April 11, 2019. Hyperalgesia, defned as hypersensitivity to pain, refers to sensitization of nociceptors to normal levels of pain. It has been reported that hyperalgesia is closely associated with infammation and neuropathic pain. 1 A number of mech- anisms, such as the development of sensitization, tissue damage, and an increased interstitial presence of infam- matory mediators, have been identifed to explain the de- velopment of hyperalgesia. 1,2 The use of platelet-rich plasma (PRP) therapy has be- come increasingly common, especially in plastic sur- gery, orthopedics, dermatology, and orthodontics. 2 During and after these procedures, pain is the most common. Although hypersensitivity after repeated PRP applications for androgenetic alopecia (AGA) has been reported in the literature, the mechanism by which PRP induces hypersen- sitivity has not yet been determined. 3 A number of impor- tant growth factors involved in tissue regeneration, such as platelet-derived growth factor (PDGF), epidermal growth From the Department of Plastic, Reconstructive, and Aesthetic Surgery and the Department of Biochemistry, School of Medicine, Necmettin Erbakan University, Konya, Turkey. Corresponding Author: Dr Bilsev Ince, Department of Plastic, Reconstructive, and Aesthetic Surgery, School of Medicine, Necmettin Erbakan University, 42080 Meram, Konya, Turkey E-mail: bilsevince@yahoo.com; Twitter: @DrBilsevInce Downloaded from https://academic.oup.com/asj/article/39/10/1139/5445341 by guest on 01 August 2022