Investigation of the Development of Hypersensitivity and Hyperalgesia After Repeated Application of Platelet-Rich Plasma in Rats: An Experimental Study

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.