ABSTRACT
BACKGROUND: Topical capsaicin shows efficacy in the treatment of brachioradial pruritus (BRP); however, its mechanisms of action remain unclear. OBJECTIVE: The effect of capsaicin on the epidermis (i.e. peripheral expression of non-neuronal sensory receptors on keratinocytes, morphological changes in innervation) is still unknown. We aimed to investigate the effect of topical capsaicin on keratinocyte expression of TRP channels and on the intraepidermal nerve fibre density (IENFD) in patients with BRP. METHODS: Thirty-one patients with BRP received an 8% capsaicin patch. Biopsies in lesional and non-lesional skin were taken to assess epidermal morphology, keratinocyte expression of TRP channels and IENFD before and 3 weeks after treatment. RESULTS: Treatment with the capsaicin patch led to a significant decrease in itch and paresthetic symptoms (P < 0.05). Keratinocyte morphology is unaltered after capsaicin therapy. Reduced keratinocyte expression of TRPV1 in lesional skin (P = 0.009; n = 9) normalized 3 weeks after treatment (P = 0.016; n = 10), but not the IENFD, which remained reduced in lesional epidermis. CONCLUSION: The normalization of the decreased TRPV1 expression may account for the effectiveness of topical capsaicin, which does not reconstitute the reduced IENFD, arguing for a role of epidermal TRPV1 in the maintenance of BRP.
Subject(s)
Antipruritics/administration & dosage , Capsaicin/administration & dosage , Epidermis/innervation , Keratinocytes/metabolism , Pruritus/drug therapy , TRPV Cation Channels/metabolism , Administration, Cutaneous , Aged , Antipruritics/pharmacology , Capsaicin/pharmacology , Cervical Vertebrae , Epidermis/drug effects , Epidermis/pathology , Female , Forearm/innervation , Humans , Keratinocytes/pathology , Male , Middle Aged , Nerve Fibers/drug effects , Peripheral Nerves/drug effects , Peripheral Nerves/pathology , Protein Biosynthesis/drug effects , Pruritus/etiology , Spinal Diseases/complications , Transdermal PatchABSTRACT
We studied the modulation of the topographic arrangement of the human ipsilateral primary somatosensory cortex following interference of nociceptive stimuli by means of dipole source analysis. Multichannel somatosensory evoked potentials were obtained by electrical stimulation of digits 1 and 5 of the left hand before, during and after the application of pain to digits 2-4 of the right hand. The primary cortical response of the SEP (N20) was obtained for dipole localization of the representation of the primary sensory cortex receiving input from digits 1 to 5. The 3D-distance between these sides was calculated for further analysis. To account for possible attentional effects recordings were performed while simultaneously to this intervention subjects were asked to turn their attention to the right or left hand in a pseudorandom order. The application of pain induced an expansion of the 3D-distance between digits 1 and 5. Focusing attention to the stimulated limb or the site of the intervention did not yield to an additional effect. Our results provide further evidence for the presence of a quickly adapting interaction between primary somatosensory areas of both hemispheres following an interference of nociceptive stimulation in SEPs. This modifying process is probably mediated by interhemispheric and intercortical connections leading to hyperexcitability of the primary sensory cortex contralateral to that receiving nociceptive input. Spatial attention does not seem to have an impact on this kind of short-term intercortical plasticity.
