Itch sensation can be inhibited by simultaneously applied cutaneous pain at the same skin site via a central mechanism. Deep muscle pain is often associated with sensory changes in the corresponding dermatome. We investigated whether experimentally induced muscle pain has any influence on histamine-induced itch and vice versa in a double blind placebo-controlled study. Experiments were performed in 18 healthy subjects. In nine individuals control iontophoresis of histamine into the forearm produced a distinct itch sensation. Another nine individuals participated in an additional experiment in which histamine and saline were iontophoresed on the forearm in a randomized double-blinded two-way crossover design after intramuscular injection of capsaicin into the ipsilateral brachioradial muscle. Capsaicin-induced muscle pain reduced itch sensation significantly. In contrast, capsaicin-induced muscle pain increased significantly after cutaneous histamine application compared to muscle pain after iontophoresis of saline (placebo). These novel data indicate that muscle pain inhibits itch and histamine increases muscle pain. A bi-directional interaction between cutaneous histamine-sensitive afferents and nociceptive muscle afferents via central mechanisms is suggested.