Chronic pain in narcolepsy reflects interacting neurobiological and psychological mechanisms: a mini-review

Chronic pain prevalence is increased in the sleep disorder narcolepsy, but the underlying reason for this remains debated. This mini review summarizes and discusses current evidence on links between narcolepsy type 1 (NT1) and type 2 (NT2) and chronic pain, exploring whether pain is best understood as a consequence of the pathophysiology or secondary to its manifestations and comorbidities. Registry-based and self-reported data indicate a high prevalence of chronic pain in NT1, while objective pain tests show inconsistent differences between NT1 and healthy individuals. This discrepancy suggests involvement of secondary mechanisms not readily captured by experimental pain testing. Comparable pain prevalence in NT1 and NT2 also speaks against orexin deficiency as a sole driver of chronic pain in NT1. Alternatively, altered dopaminergic signaling downstream of orexin could be a shared contributor to pain in NT1 and other fatigue-related conditions. Finally, the presence of activating autoantibodies in NT1 suggests a possible immune-mediated component for some patients. Overall, chronic pain is highly prevalent in both NT1 and NT2. It likely arises from a combination of neurobiological and psychological factors, with immune mechanisms as a possible additional contributor, rather than, in NT1, orexin dysfunction alone. This perspective highlights the clinical need for more holistic treatment approaches and for future studies with improved case-control matching, larger NT1 samples, especially among patients with chronic pain, and more detailed comparisons with NT2.