early stages of damage, when receptors or skin nerve end- ings are impaired but undetectable by standard nerve con- duction studies. Key words Capsaicin • Neuropathy • Neurophysiology • Skin nerve endings • Double peak Introduction Distal sensory neuropathies are common but not easily diagnosed in the early stage because of limited ability of conventional nerve conduction studies to document func- tional changes in the extreme segments of sensory nerve fibres. These fibres are early involved in distal sensory neu- ropathies and, if easily detected, they could allow an early diagnosis and predict clinical efficacy or futility of prospective therapies [1]. Capsaicin is the active ingredient in hot chili peppers that, if repeatedly applied on human skin, induces a complete epi- dermal and superficial dermal denervation at the site of appli- cation followed by subsequent regeneration [2–5]. Epidermal nerve fibres (ENFs) are unmyelinated somatic nerve fibres arising from small-size dorsal root ganglion neurons that project to the skin. These fibres have been shown to be capsaicin-sensitive nociceptors and they are an ideal target for the study of nerve regeneration [6–8]. Skin biopsy and immunohistochemical studies have been shown as useful tools to investigate the behaviour of epidermal and dermal nerve fibres and the relationship between clinical symptoms and morphological findings after chemical degeneration by using local capsaicin appli- cations. Simone and colleagues showed that an intradermal injection of capsaicin produces a decreased sensitivity to pain from mechanical stimuli and nearly eliminated heat- evoked pain. These symptoms resulted from rapid degener- ation of intracutaneous nerve fibres [5]. Neurol Sci (2007) 28:264–269 DOI 10.1007/s10072-007-0833-x I. Aprile • P. Tonali • E. Stalberg • E. Di Stasio • P. Caliandro • M. Foschini • G. Vergili • L. Padua Double peak sensory responses: effects of capsaicin ORIGINAL Received: 21 May 2007 / Accepted in revised form: 31 August 2007 Abstract The aim of this study is to verify whether degen- eration of skin receptors or intradermal nerve endings by topical application of capsaicin modifies the double peak response obtained by submaximal anodal stimulation. Five healthy volunteers topically applied capsaicin to the finger- tip of digit III (on the distal phalanx) four times daily for 4–5 weeks. Before and after local capsaicin applications, we studied the following electrophysiological findings: compound sensory action potential (CSAP), double peak response, sensory threshold and double peak stimulus intensity. Local capsaicin application causes disappearance or decrease of the second component of the double peak, which gradually increases after the suspension of cap- saicin. Conversely, no significant differences were observed for CSAP, sensory threshold and double peak stimulus intensity. This study suggests that the second component of the double peak may be a diagnostic tool suitable to show an impairment of the extreme segments of sensory nerve fibres in distal sensory axonopathy in the I. Aprile () • P. Tonali • P. Caliandro • M. Foschini • G. Vergili L. Padua Fondazione Don Carlo Gnocchi Via Maresciallo Caviglia 30, I-00194 Rome, Italy e-mail: iaprile@dongnocchi.it P. Tonali • P. Caliandro • L. Padua Institute of Neurology Università Cattolica del Sacro Cuore Rome, Italy E. Stalberg Department of Clinical Neurophysiology Uppsala, Sweden E. Di Stasio Institute of Biochemistry and Clinical Biochemistry Università Cattolica del Sacro Cuore, Rome, Italy