ENISNIP : European Network on Inherited Sensory Neuropathies and Insensitivity to Pain

Patients with monogenic pain-insensitivity disorders do not respond to painful stimuli and sustain repeated trauma with potentially fatal complications. Limited awareness of these rare conditions, small patient cohorts, lack of standardized phenotype information, low diagnostic yield of genetic testing and only partial recognition of disease mechanisms have been largely precluding clinical research. ENISNIP, a European network of clinicians, geneticists and basic scientists will tackle these hurdles and (1) ensure rapid diagnosis for pain-insensitivity disorders, (2) gather cross-sectional data, (3) advance genetic diagnosis and gene discovery through state-of-the-art genomics and innovative variant filtering procedures integrating additional omics levels, disease modelling and regular re-evaluation of variants’ impact on disease, and (4) track disease mechanisms. ENISNIP will bring accurate genetic diagnosis and counselling to individuals with pain-insensitivity disorders and support establishing standards of diagnosis and care. We envision delivering meaningfully sized, well-phenotyped and – genotyped patient cohorts, new insights into the molecular basis of pain-insensitivity disorders, paving the way for preclinical experimental treatment trials and clinical research. With regard to further translational capacity, genes and mechanisms related to rare Mendelian pain- insensitivity disorders are exceptional in their potential to uncover novel molecular targets to treat chronic pain, which constitutes one of the major global socioeconomic and health care burdens.