Sunburn—A human inflammatory pain model for primary and secondary hyperalgesia

Abstract

In this issue of the Scandinavian Journal of Pain, Rossler et al. escribe an experimental model that confirms the central origin f pin prick hyperalgesia in the human sunburn model [1]. UVrradiation has been used extensively as a translational model for nflammatory pain and hyperalgesia using rodents [2,3], pigs [4] nd human volunteers [5,6]. The time course of hyperalgesia develpment is similar in different species, with an onset latency of –6h and a peak responsiveness 24–48h after irradiation, thus epresenting a useful experimental model for drug testing. Upon rradiation of small skin patches (about 1 cm2), only primary yperalgesia has been detected in human and rodents [2,3]. As a ultitude of mediators are being released upon UV-irradiation of he skin, including eicosanoids (e.g. PGE2, PGD2, PGF2a, LTB-4, 12ETE), cytokines (e.g. IL-1, IL-6, IL-8, TNF-alpha), growth factors e.g. TGF-beta, VEGF, NGF) vasoactive amines and neuropeptides e.g. histamine, bradykinin, CGRP), researchershavemainly focused n the primary hyperalgesia that is evident in the inflamed skin. ome of these can be accounted for the inflammatory UV-induced esponses, such as erythema (i.e. CGRP) or heat hyperalgesia (e.g. GE2, bradykinin) and sensitization of heat-sensing ion channels e.g. TRPV1). Another cardinal symptom of UV-inflammation in uman skin is a profound peripheral mechanical sensitization. here is recent evidence for a role of mechanical sensitization f heat insensitive (CM) fibers after UV-irradiation to particularly trongmechanical stimuli [3]. Primarymechanicalhyperalgesiahas een linked to CXCL5 in an elegant translational study [7]. In this issue, Rossler et al. describe a humanUVBmodel inwhich hey use larger irradiation areas [1]. Albeit no spontaneous pain is nduced in the area of the sunburn, they found a large area of secndary mechanical hyperalgesia to pin prick in the subjects [8]. n order to prove the central origin, they used an anesthetic strip echnique to exclude neuronal peripheral spread of hyperalgesia. he anesthetic strip did not reduce the area of secondary hyperlgesia, and thus, it can be assumed that it is of central origin. xperimentally, secondarymechanicalhyperalgesia canbe induced