Peripheral Modulatory Effects of Catecholamines in Inflammatory and Neuropathic Pain

Abstract

Publisher Summary Basic science and clinical studies indicate that the sympathetic nervous system (SNS) may play a role in pathological states associated with pain and hyperalgesia, such as inflammation and neuropathic pain. Recent psychophysical studies provide pharmacological evidence that noradrenaline may influence pain sensation in normal human subjects. Studies indicate that norepinephrine (NE) produces hyperalgesia to heat stimuli when administered into the skin of normal subjects. The earlier animal studies utilized a mechanical search stimulus to identify nociceptors. More recent studies have recognized the presence of “silent” nociceptors in skin that are mechanically insensitive. In a recent psychophysical study, the effects of NE on cutaneous hyperalgesia in humans are investigated, using topical application of capsaicin as a model to induce hyperalgesia. Capsaicin is known to sensitize C-fibers to heat and lower the pain threshold to mechanical stimuli. The decrease in heat pain threshold (hyperalgesia) following capsaicin administration is prolonged at the site where NE is iontophoresed but not at the saline site, suggesting that NE increased heat hyperalgesia in skin treated with topical capsaicin. These effects of NE in humans are consistent with the neurophysiological observations in animals that NE and sympathoneural stimulation increase nociceptor discharges in inflamed skin.