AUTHOR=Smith Peter A. TITLE=Neuropathic pain; what we know and what we should do about it JOURNAL=Frontiers in Pain Research VOLUME=Volume 4 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2023.1220034 DOI=10.3389/fpain.2023.1220034 ISSN=2673-561X ABSTRACT=Neuropathic pain can result from injury to, or disease of the nervous system. It is notoriously difficult to treat. Peripheral nerve injury promotes Schwann cell activation and invasion of immunocompetent cells into the site of injury, spinal cord and higher sensory structures such as thalamus and cingulate and sensory cortices. Various cytokines, chemokines, growth factors, monoamines and neuropeptides effect two-way signalling between neurons, glia and immune cells. This promotes sustained hyperexcitability of primary afferents that is crucial for onset and persistence of pain as well as misprocessing of sensory information in the spinal cord and supraspinal structures. Much of the current understanding of pain aetiology and identification of drug targets derives from studies of the consequences of peripheral nerve injury in rodent models. Although a vast amount of information has been forthcoming, the translation of this information into the clinical arena has been minimal. Few, if any, major therapeutic approaches have appeared since the mid 1990’s. This may reflect failure to recognize differences in pain processing in males versus females, differences in cellular responses to different types of injury and differences in pain processing in humans versus animals. Basic science and clinical approaches which seek to bridge this knowledge gap include better assessment of pain in animal models, use of pain models which better emulate human disease, and stratification of human pain phenotypes according to quantitative assessment of signs and symptoms of disease. This can lead to more personalized and effective treatments for individual patients.