Ectopic Pacemaker Theory

Neuropathic pain is thought to result when sensory neurons generate impulses at abnormal (ectopic) locations, for example at sites of nerve injury or demyelination. In the peripheral nervous system, in addition to firing spontaneously, these ectopic pacemaker sites are often excited by mechanical forces applied to them during movement. The result is spontaneous and movement-evoked pain. Damage to the central nervous system, such as in stroke or trauma, may cause ectopic firing of central origin, or render brain circuits hyperexcitable. In the ectopic pacemaker theory, ectopic afferent firing is a primary source of spontaneous pain; it initiates and sustains central sensitization that manifests clinically as neuropathic hypersensitivity.1 In addition, various neuropeptides such as the cytokine tumor necrosis factor-alpha, neurotensin,somatostatin are released in response to inflammation, specifically macrophage activation.