Brain (1994), 117, 385-396 Different patterns of hyperalgesia induced by experimental inflammation in human skin S. Kilo, 1 M. Schmelz, 1 M. Koltzenburg 2 and H. O. Handwerker 1 department of Physiology and Biocybernetics, University of Erlangen-Nurnberg and the 2 Department of Neurology, University of Wiirzburg, Germany Correspondence to: Dr Sonja Kilo, Department of Physiology and Biocybernetics, University of Erlangen- Nurnberg, Universitdtsstr. 17, D-91054 Erlangen, Germany Summary Different types of hyperalgesia were studied after experimental induction of inflammation in small skin areas of healthy volunteers either by topical application of capsaicin solution (1 % in 70% ethanol) or by briefly freezing a skin area of similar size to —28°C. Sensory tests were performed 30 min after capsaicin application and 22 h after freeze lesions. Heat pain thresholds were lowered after both treatments, probably due to nociceptor sensitization. Hyperalgesia to four types of mechanical stimulation was studied, (i) Hyperalgesia to punctate stimuli was encountered at the skin site directly affected by the noxious chemical or freeze stimulus (1 ° zone) and in the surrounding skin (2 ° zone) in both models though the area of 2° hyperalgesia to punctate stimuli after freezing was smaller than after capsaicin. (ii) Hyperalgesia to gently brushing the skin was prominent after capsaicin in 1 ° and 2 ° zone, but almost absent after freezing. It was concluded that both hyperalgesia to punctate stimuli and brush-evoked pain are due to central Key words: pain; C-fibres; A-fibres; nociception; sensitization nervous plasticity changes rather than nociceptor sensitization. As revealed by differential nerve blocks, brush-evoked pain is mediated by low threshold mechanosensitive Afl-fibres, whilst hyperalgesia to punctate stimuli can be elicited when only C- fibres conduct. In contrast to hyperalgesia to punctate stimuli it requires continuous background discharges in nociceptor units. (Hi) Pressure hyperalgesia to tonic stimulation with a blunt probe was encountered in the I ° zone of both types of inflammation and is probably due to recruitment of sensitized nociceptor units, (iv) Impact hyperalgesia was studied by shooting small bullets against the skin at predetermined velocities. It was found in the 1 ° zone after freezing and absent in the capsaicin model. Differential nerve blocks revealed that it is probably mediated by sensitized C-fibres. In conclusion, different types of inflammatory changes may result in characteristic different patterns of hyperalgesia. Introduction Hyperalgesia to mechanical and thermal stimuli is often found after injury of the skin or partial lesions of peripheral nerves. It is now known that several types of hyperalgesia can be distinguished on the basis of topography and stimulus quality. Insights into the nature of different types of hyperalgesia have been derived mainly from studies of small skin traumas, experimentally induced in healthy volunteers. Some decades ago Lewis (1936, 1942) and Hardy et al. (1950, 1952) characterized two zones of abnormal pain sensitivity following focal experimental skin injuries: (i) the primary zone directly affected by the injurious stimulus; (ii) the secondary zone of apparently undamaged tissue surrounding the focus of tissue injury. More recently, it became clear that different hyperalgesias can be distinguished according to stimulus modalities and qualities. For example, increased sensitivity to © Oxford University Press 1994 mechanical stimulation may comprise a state in which abnormally strong pain is evoked by punctate stimuli (LaMotte et al., 1991), or a state in which the subject is hyperalgesic to tonic pressure with blunt probes (Culp etai, 1989; Koltzenburg etal, 1992). In a third form of mechanical hyperalgesia—often referred to as allodynia —pain is elicited by gently stroking the skin, e.g. with a soft brush or a swab of cotton wool (Lewis, 1942; Hardy et al., 1950). These different types of mechanical hyperalgesia are apparently based on different neural mechanisms and may coexist after experimental skin injury (LaMotte et al., 1991; Koltzenburg et al., 1992). Exact description and analysis of the neural mechanisms of experimentally induced hyperalgesias may also be of clinical interest since similar forms of hyperalgesia have been encountered in patients suffering from neuropathies or other