Defining cellular mechanisms important for painful chemotherapy‐related neuropathy using long‐term primary cultures of nociceptors

Painful chemotherapy‐induced peripheral neuropathy (CIPN) is an increasingly common condition for which no adequate treatments are known. Prominent toxic effects of chemotherapeutic drugs such as paclitaxel include debilitating ongoing pain. Because of the complexity of the tissues involved in vivo , there is a need for simple models that capture essential features of CIPN for mechanistic analysis. Lamberti et al. employ long‐term culture of dissociated nociceptors to begin defining physiological and molecular mechanisms underlying persistent spontaneous activity (SA) induced in vitro by repeated application of paclitaxel. They demonstrate major contributions to progressively increasing SA from potentiated depolarizing spontaneous fluctuations of membrane potential (DSFs, which were only recently recognized to control the timing and frequency of irregular spontaneous discharge in nociceptors), and they provide strong evidence that the SA and DSFs involve enhanced function and/or expression of Nav1.8, TRPV1, TRPA1, and TRPM8 channels. This model system offers considerable promise for further defining the mechanisms of SA important for driving ongoing pain after CIPN. Comment on: https://doi.org/10.1111/febs.70517 .