Electrophysiological characterization of ectopic spontaneous discharge in axotomized and intact fibers upon nerve transection: a role in spontaneous pain?

Many patients experience positive symptoms after traumatic nerve injury. Despite the increasing number of experimental studies in models of peripheral neuropathy and the knowledge acquired, most of these patients lack an effective treatment for their chronic pain. One possible explanation might be that most of the preclinical studies focused on the development of mechanical or thermal allodynia/hyperalgesia, neglecting that most of the patients with peripheral neuropathies complain mostly about spontaneous forms of pains. Here, we summarize the aberrant electrophysiological behavior of peripheral nerve fibers recorded in experimental models, the underlying pathophysiological mechanisms, and their relationship with the symptoms reported by patients. Upon nerve section, axotomized but also intact fibers develop ectopic spontaneous activity. Most interestingly, a proportion of axotomized fibers might present receptive fields in the skin far beyond the site of damage, indicative of a functional cross talk between neuromatose and intact fibers. All these features can be linked with some of the symptoms that neuropathic patients experience. Furthermore, we spotlight the consequence of primary afferents with different patterns of spontaneous discharge on the neural code and its relationship with chronic pain states. With this article, readers will be able to understand the pathophysiological mechanisms that might underlie some of the symptoms that experience neuropathic patients, with a special focus on spontaneous pain.