Transient inhibition of the human motor cortex by capsaicin- induced pain. A study with transcranial magnetic stimulation Simona Farina a , Massimiliano Valeriani b , Tiziana Rosso a , Salvatore Aglioti c , Stefano Tamburin a , Antonio Fiaschi a , Michele Tinazzi a, * a Dipartimento di Scienze Neurologiche e della Visione, Sezione di Neurologia Riabilitativa, Universita ` di Verona, Verona, Italy b Dipartimento di Neurologia, Universita’Cattolica del Sacro Cuore, Rome, Italy c Dipartimento di Psicologia, Universita ` di Roma ‘La Sapienza’, and IRCCS, Fondazione S. Lucia, Rome, Italy Received 12 July 2001; received in revised form 14 September 2001; accepted 14 September 2001 Abstract Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the left motor cortex were recorded from the right first dorsal interosseous (FDI), abductor pollicis brevis (APB), abductor digiti minimi (ADM), flexor carpi radialis (FCR), extensor carpi radialis (ECR) in 17 normal subjects, before and after painful application of capsaicin on the skin overlying the right FDI and FCR muscles. The amplitude of MEPs from the FDI and FCR was significantly reduced from 20 to 30 min after the application of capsaicin over the FDI and FCR muscles, respectively, then progressively returned to the basal values. A similar trend of MEPs inhibition was observed for APB and FCR muscles, but this reduction was not significant. Indices of peripheral nerve (M-wave) and spinal cord excitability (F and H waves) did not change throughout the experiments. Motor cortex inhibition induced by tonic cutaneous pain is maximal to muscles adjacent to the painful area. This inhibition may be due to the activation of the C fibres which mediate ‘slow’ nociception and might be important to alert subject to possible phasic nociceptive events that may occur close to the painful area. q 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Pain; Motor cortex; Inhibition; Capsaicin; Motor evoked potentials; Transcranial magnetic stimulation Several studies both in animals and humans have dealt with the effects of phasic cutaneous and subcutaneous pain- ful stimulation of the limbs on spinal cord reflexes [4,8,11,17,18]. There is also good evidence that tonic cuta- neous pain has a modulatory effect on spinal circuitry [1,5,12,13]. In these studies experimental tonic cutaneous pain has been obtained by intradermal or topical application of capsaicin, which produces a local burning pain lasting about 80 min. The effect of tonic cutaneous pain on the motor cortex excitability is still unknown. Even though positron emission tomography (PET) studies have shown a regional increase of cortical blood flow in the contralateral primary motor cortex (M1) after tonic painful stimulation of the skin [3,7], the functional role of this M1 activation is unclear. For this reason, we studied the effect of experimen- tal acute tonic pain on motor cortex excitability by means of transcranial magnetic stimulation (TMS). To this aim, we investigated whether (i) capsaicin pain is able to change the contralateral motor cortex excitability and (ii) if this change is selective for the muscle closest to the painful skin or involves further muscles. Seventeen healthy subjects were enrolled in the study, which included two experiments: Experiment 1 (n ¼ 11, age 26 to 30 years, six males and five females) and Experi- ment 2 (n ¼ 6, age 28 to 39 years, four males and two females). Written informed consent was obtained from all volunteers and the protocol was approved by the local Ethi- cal Committee. A capsaicin 3% commercial preparation was applied under an occlusive dressing on the skin close to the first dorsal interosseus (FDI) muscle (distal part of metacarpus of the right thumb) in Experiment 1 and on the skin close to the flexor carpi radialis (FCR) muscle in Experiment 2 (about 3 cm medial to the motor point of FCR). Capsai- cin-induced pain was numerically rated by the subjects on a visual analogue scale (VAS), comprising a continuum from ‘no sensation’ ¼ 0, to ‘the worst imaginable Neuroscience Letters 314 (2001) 97–101 0304-3940/01/$ - see front matter q 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3940(01)02297-2 www.elsevier.com/locate/neulet * Corresponding author. Tel.: 139-045-807-2601; fax: 139-045- 807-2100. E-mail address: michele.tinazzi@mail.azosp.vr.it (M. Tinazzi).