Central origin of pinprick hyperalgesia adjacent to an UV-B induced inflammatory skin pain model in healthy volunteers

Abstract

Background and purposeThe UV-B model is an established pain model of different types of hyperalgesia in animal and human pain research. Beside the skin region of the sunburn in human volunteers pinprick hyperalgesia has been described in a large zone of non-inflamed skin adjacent to the sunburn. However, there are opposing results on the existence of pinprick hyperalgesia and most notably a controversial discussion is still on-going whether this mechanical hyperalgesia in the undamaged tissue adjacent to and at some distance from the site of inflammation is of peripheral or central origin. We therefore addressed this in our study by hypothesising that pinprick hyperalgesia around a circular spot of UV-B inflamed skin is not reduced by a superficial local anaesthetic block and therefore underlies centrally mediated mechanisms. MethodsThis exploratory study was conducted in a prospective, controlled, randomised, single-blinded fashion in relation to the study hypothesis in 12 healthy volunteers. Before circular irradiation with UV-B light (3-times the individual minimal erythema dose at both thighs), a strip of continuous intradermal local anaesthetic block with lidocaine 2% was established via two single plasmaphoresis hollow fibres. These were positioned perpendicular to one thigh overlapping on the midline of the leg at the distal part of the planned irradiation site, and compared with the contralateral control side without anaesthetic block. The local anaesthetic block was established and then maintained via a syringe pump. The area of pinprick hyperalgesia was measured by pricking on a large skin surface including 360° around the circular irradiation site. This was done with a slightly painful pin (256mN) until 8h after irradiation. Primary outcome was the area of pinprick hyperalgesia in the skin adjacent to the sunburn at 8h. ResultsLarge areas of mechanical hyperalgesia to pinprick surrounding the adjacent skin of the sunburn developed on both sides after 8h without any significant difference between the side of the anaesthetic strip showing an area of 72.6±39.7cm2 (mean±SD) and the control side (59.1±20.1cm2); p=0.24. Moreover, mechanical hyperalgesia to various pin stimuli of different strength was unchanged by the anaesthetic block. ConclusionsThis trial provides evidence that the development of mechanical hyperalgesia surrounding an experimental sunburn was not influenced by continuous peripheral afferent blockade with local anaesthetic at 8h after UV-B irradiation. Our data support the hypothesis that in the UV-B model peripheral nociceptive afferent input of inflamed skin may enhance central hypersensitivity of mechanosensitive nociceptors in a larger receptive field far beyond the inflamed skin. Furthermore, these findings are in line with other pain models demonstrating comparable central hypersensitivity around the site of injury. ImplicationsAs for other pain models this finding provides further evidence that the UV-B model offers secondary mechanical hyperalgesia in addition to its known primary hyperalgesia. Consequently, this is a further validation for the utilisation of the UV-B model in human pain research.