Human surrogate models of neuropathic pain

Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system (Merskey and Bogduk, 1994). Current efforts to refine this definition focus on the terms ‘dysfunction’ and ‘nervous system’ with the intention to clarify that there has to be an identifiable lesion or disease process affecting the somatosensory system. Experimental models of neuropathic pain according to either one of these definitions are expected to imitate mechanisms of nerve damage within the peripheral or central parts of the somatosensory system and the ensuing processes of degeneration and regeneration. Whereas this approach to model the etiology and pathophysiology of the underlying disease process is the focus of various animal models of neuropathic pain, for obvious ethical reasons these processes cannot be induced in healthy human subjects. Human surrogate models of neuropathic pain focus on the sensory signs and symptoms. On one hand, this is a limitation. On the other hand, the investigation of sensory symptoms exploits the unique human capacity for verbal communication, which allows the direct assessment of quality and intensity as well as location and duration of ongoing signs (pain, paraesthesia) and evoked signs (evoked pain, sensory loss) without relying on reflexes. In addition, laboratory studies in human surrogate models with electrophysiological and imaging techniques are immediately transferable to patient populations