Disrupted spatial but not temporal aspects of nociceptive processing determine painful polyneuropathies

Abstract Polyneuropathy remains a diagnostic and clinical challenge, with limited understanding of the mechanisms underlying painful and nonpainful phenotypes. While previous studies have examined various characteristics of these patients, the temporal and spatial dynamics of endogenous pain modulation remains not fully elucidated. In this study, offset analgesia (OA) and spatial summation of pain (SSp) were used as measures of pain modulation in individuals with distal symmetric polyneuropathy, stratified by the presence (n = 30) or absence of pain (n = 30), and compared with healthy controls (n = 30). All participants underwent quantitative sensory testing and assessments of OA and SSp using a thermal stimulator applied to the dorsum of the foot. Patients with painful polyneuropathy exhibited enhanced SSp compared with the pain-free polyneuropathy group and healthy controls ( P < 0.05), and impaired OA compared with healthy controls ( P < 0.05). The pain-free neuropathy group showed less efficient OA and a slightly enhanced SSp, but this finding did not reach significance. The data suggest that changes in spatial summation were primarily driven by heightened pain responses to nociceptive input from smaller areas, rather than larger ones. Notably, spatial summation and the effects of OA were found to be correlated, irrespective of pain diagnosis. These findings underscore specific impairments in endogenous pain modulation in individuals with painful neuropathy, thus advancing our understanding of its pathophysiological mechanisms. They further highlight the differential roles of spatial and temporal dynamics in pain modulation across various neuropathic populations, offering promising avenues for improved diagnostics and prognostics related to polyneuropathy-associated pain.