Genomics of Neuropathic Pain

Neuropathic pain stems from a lesion or disease of the somatosensory system. Disorders characterised by neuropathic pain vary considerably in their etiology and frequency. Hereditary conditions are usually monogenic, and their causal genetic variants are rare, identified through linkage studies in multi-generation pedigrees. They lie on a spectrum, from painful to painless, with the latter class of conditions also engendered by a disrupted somatosensory system. Acquired neuropathic pain conditions result from injury, such as nerve damage inflicted during surgery, or another primary disease, such as diabetes or cancer. For these conditions, there are many genetic risk factors, each of which individually contributes a small risk, and large cohort studies of unrelated individuals are necessary to identify these factors. The genetic variants implicated in both hereditary and acquired conditions shed light on the molecular pathophysiology underlying neuropathic pain, which has the potential to improve diagnostic and therapeutic efficacy. The current landscape informed by genetic studies shows an enrichment for neurotransmission mediators for painful hereditary conditions, neuronal maintenance mediators for painless hereditary conditions, and neuroimmune interactions for acquired neuropathic pain conditions.