Centrally mediated sensory decline induced by differential C-fiber stimulation.

It is increasingly recognized that pain-induced plasticity may not only provoke sensory gain (hyperalgesia), but also sensory decline, i.e. hypoesthesia and hypoalgesia. We investigated perceptual changes by conditioning electrical stimulation of peptidergic C-nociceptors differing in stimulation frequencies and duty cycles at the left forearm. Four noxious electrical stimulation paradigms (Stim1: 0.5 Hz, continuously; Stim2: 20 Hz, continuously; Stim3: 1s 20 Hz train, 1s break; Stim4: 1s 20 Hz train, 2s break) were applied. Stim1 led to mechanical hyperalgesia and hypoesthesia. In contrast, Stim2 generated both hypoalgesia and hypoesthesia, which was not blocked by an anaesthetic ring around the stimulated skin area and markedly exceeded the primary stimulation site, providing evidence for a centrally mediated mechanism. Finally, when electrical high frequency trains were applied with two different duty cycles (i.e. Stim3 and 4), both stimulation paradigms produced hypoesthesia. However, only high frequency trains interrupted by the shorter inter train interval led to hypoalgesia. In contrast, high frequency trains interrupted by the longer inter train interval produced significant mechanical hyperalgesia. In summary, we describe here that depending on the applied frequencies and duty cycles, either sensory gain (i.e. hyperalgesia) or sensory decline (i.e. hypoesthesia and hypoalgesia) can be induced. Sensory decline was found to be centrally mediated. Underlying mechanisms may include differential recruitment of inhibitory and facilitating gain control systems leading to homo- and heterosynaptic inhibition or facilitation at the level of the spinal cord or interference of noxious input with tactile processing in the cortex.