Neuropathy means nerve disease or damage.Symptoms can range from numbness or tingling, to pricking sensations (paresthesia), or muscle weakness. Areas of the body may become abnormally sensitive leading to an exaggeratedly intense or distorted experience of touch (allodynia). In such cases, pain may occur in response to a stimulus that does not normally provoke pain. Severe symptoms may include burning pain (especially at night), muscle wasting, paralysis, or organ or gland dysfunction. Damage to nerves that supply internal organs may impair digestion, sweating, sexual function, and urination. Different biomarkers are used for estimating neuropathy of small nerve fibres like the histamine-induced skin flare response and intra-epidermal fibres (IEF),contact heat evoked potential (CHEP) and quantitative sensory testing (QST).Among these biomarkers,

Contact heat-evoked potentials (CHEPs) have become a promising procedure for assessing small-fiber sensory nerves.It's potential as a physiological signature of neuropathic pain symptoms has not been fully determined.

A total of 188 patients (115 men) with length-dependent sensory symptoms and reduced intraepidermal nerve fiber (IENF) density at the distal leg were enrolled to perform CHEP, quantitative sensory testing, and nerve conduction study so that the diagnostic efficacy in examining small-fiber sensory nerve degeneration, its relationship with skin innervations, and clinical correlates with sensory symptoms can be evaluated. Fifty-seven age- and sex-matched controls were enrolled for comparison of CHEP and skin innervation. Among patients with neuropathy, 144 patients had neuropathic pain and 64 cases had evoked pain. CHEP amplitudes showed the highest sensitivity for diagnosing small-fiber sensory nerve degeneration and exhibited the strongest correlation with IENF density in multiple linear regression as compared with quantitative sensory testing and nerve conduction study parameters. Contact heat-evoked potential amplitudes were strongly correlated with the degree of skin innervation in both patients with neuropathy and controls. The slope of the regression line between CHEP amplitude and IENF density was higher in patients with neuropathy than in controls. Patients with evoked pain had higher CHEP amplitude than those without evoked pain,which was  independent of IENF density. Receiver operating characteristic analysis remarked that CHEP had better performance in diagnosing small-fiber sensory nerve degeneration than thermal thresholds.CHEPs showed superior classification accuracy with respect to evoked pain. At last it was interpretated that CHEP appears as a sensitive tool to evaluate pathophysiology of small-fiber sensory nerve and serves as a physiological signature of neuropathic pain symptoms.