Neuropathic pain can occur due to trauma to the central or peripheral nervous system. However, neuropathy is also associated with diseases such as diabetes, accounting for nearly 30% of cases. The underlying cause of neuropathic pain is diverse and for some patients, it remains to be elucidated. Due to the widespread symptoms and causes of neuropathy, effective treatment has been challenging.
Depression is common in individuals suffering from chronic pain and the kynurenine pathway (KP) has been shown to be altered in both of these states. In a recent study by Dr. Alexandre Maganin and colleagues, they investigated the potential role that KP plays in neuropathy pathogenesis. Indoleamine 2,3-dioxygenase-1 (IDO1) inhibition reduced pain in the spared nerve injury model. Interestingly, expression of IDO1 in the spinal cord after injury was observed in hematopoietic cells and not in resident spinal cord cells. Specifically, dendritic cells (DCs) were shown to be the source of IDO1. Following nerve injury, DCs infiltrate the lesion site and in DC-depleted mice, the increase of IDO1 was not observed. DCs play a potential role in the development of neuropathic pain via KP activation. Direct injection of KP metabolites demonstrated that 3-hydroxykynurenine (3-Hk) and Quinolinic acid (QA) drive neuropathic pain. Taken together, KP activation contributes to neuropathic pain and pharmacological inhibition of the KP may alleviate neuropathic pain, however, further research is warranted.