Papers of the Week

Neuropathic pain (NP) constitutes a significant burden for individuals, manifesting as nociceptive anaphylaxis, hypersensitivity, and spontaneous pain. Previous research has suggested that the analgesic effects of NP are mediated by dopamine (DA) neurons in the ventral tegmental region (VTA) through projections to various brain regions. A decrease in VTA dopamine neurons following NP may contribute to prolonged pain. It has been revealed that inflammatory activation triggers necroptosis by stimulating mixed lineage kinase domain-like protein (MLKL), leading to progressive neuronal demise. Recent research from many studies has revealed that that IL-17-induced necroptosis plays an important role in neuroinflammation and neuronal damage. To our knowledge, few studies have hitherto investigated how IL-17-induced necroptosis may contribute to neuropathic pain. Hydrogen sulfide (HS) treatment is commonly used for neuropathic pain, although the exact mechanisms remain unclear. Sodium hydrosulfide (NaHS), a common HS delivery method in medicine, has also been shown to exert neuroprotective effects against neuropathic pain. This study aimed to investigate the link between IL-17-induced necroptosis of dopamine neurons in the VTA and neuropathic pain. Additionally, we explored whether HS treatment could reduce the loss of VTA dopamine neurons, thereby lowering neuropathic pain in a chronic constriction injury (CCI) model.