Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Despite the discovery of ion channels that are activated by protons, we still know relatively little about the signaling of acid pain. We used a novel technique, iontophoresis of protons, to investigate acid-induced pain in human volunteers. We found that transdermal iontophoresis of protons consistently caused moderate pain that was dose-dependent. A marked desensitization occurred with persistent stimulation, with a time constant of approximately 3 min. Recovery from desensitization occurred slowly, over many hours. Acid-induced pain was significantly augmented in skin sensitized by acute topical application of capsaicin. However, skin desensitized by repeated capsaicin application showed no significant reduction in acid-induced pain, suggesting that both capsaicin-sensitive and insensitive sensory neurons contribute to acid pain. Furthermore, topical application of non-steroidal anti-inflammatory drugs (NSAIDs) significantly attenuated acid-evoked pain but did not affect the heat pain threshold, suggesting a specific interaction between NSAIDs and peripheral acid sensors. Subcutaneous injection of amiloride (1 mm) also significantly inhibited the pain induced by iontophoresis of acid, suggesting an involvement of acid-sensing ion channel (ASIC) receptors. Conversely, iontophoresis of acid over a wide range of skin temperatures from 4 to 40 degrees C produced only minor changes in the induced pain. Together these data suggest a prominent role for ASIC channels and only a minor role for transient receptor potential vanilloid receptor-1 as mediators of cutaneous acid-induced pain.

Original publication

DOI

10.1523/JNEUROSCI.2619-04.2004

Type

Journal article

Journal

J Neurosci

Publication Date

01/12/2004

Volume

24

Pages

10974 - 10979

Keywords

Acid Sensing Ion Channels, Administration, Cutaneous, Adult, Amiloride, Analgesics, Anti-Inflammatory Agents, Non-Steroidal, Capsaicin, Diclofenac, Female, Forearm, Hot Temperature, Humans, Hydrochloric Acid, Hydrogen-Ion Concentration, Hyperalgesia, Ibuprofen, Injections, Subcutaneous, Ion Channels, Iontophoresis, Male, Membrane Proteins, Middle Aged, Nerve Tissue Proteins, Pain, Pain Measurement, Pain Threshold, Refractory Period, Electrophysiological, Single-Blind Method, Sodium Channels, TRPV Cation Channels