Cellular and molecular basis of neuropathic pain

Neuropathic pain is a devastating type of pain that significantly reduces the quality of life of affected people. Traditionally considered as mechanistically distinct from pain induced by classical inflammatory states, studies continue to reveal more commonalities than differences, with a whole host of pathological changes in the environment of local peripheral nerves accompanying chronic neuropathic pain conditions. This narrative review provides an overview of the cellular and molecular drivers of neuropathic pain, highlighting some of the seminal publications from past and present. We discuss both neuronal and non-neuronal mechanisms contributing to neuropathic pain (eg, immune and stromal cell dysregulation). Particular attention is given to studies involving human cohorts which, until recently, have been less common in the field, due to the difficulties in accessing relevant tissues, like nervous system samples. The consequences of recent findings for analgesic drug development are also discussed, both in the context of neuropathic and non-neuropathic pain.