Hyperglycemia and Central Obesity Disrupt Conditioned Pain Modulation: A Single-Blind Crossover Randomized Controlled Trial

Abstract

Hyperglycemia and high adiposity are risk factors for pain in diabetes. To clarify these links with pain, the effects of a glucose load on sensory detection, pain sensitivity, conditioned pain modulation (primary aims), and autonomic and endothelial functions (secondary aims) were examined in 64 pain-free participants: 22 with normal adiposity (determined by dual-energy X-ray absorptiometry), 29 with high adiposity, and 13 with combined high adiposity and elevated glycated hemoglobin (HbA1c; including prediabetes and type 2 diabetes). Participants ingested either 37.5 g glucose or 200 mg sucralose (taste-matched) in the first session and crossed over to the other substance in the second session 1 month later. At baseline, painful temple cooling (the conditioning stimulus) inhibited pressure- and heat-pain in the ipsilateral arm (the test stimuli) immediately after cooling ceased (partial η2’s > .32). Glucose ingestion weakened pressure-pain inhibition irrespective of HbA1c levels (partial η2 = .11). However, a larger reduction in pressure-pain inhibition after ingesting glucose was associated with a higher waist/hip ratio (r = .31), suggesting a role of central obesity. Heat-pain inhibition was absent at baseline in unmedicated participants with elevated HbA1c, and these participants reported more occlusion-induced pain after ingesting glucose (partial η2’s > .17). Glucose ingestion interfered with parasympathetic activity in all participants (partial η2 = .11) but did not affect endothelial function (measured by reactive hyperemia) or alter other sensations (eg, feet vibration detection). The disruptive effect of hyperglycemia on conditioned pain modulation increases in line with central obesity, which might facilitate pain in diabetes. PerspectiveIngesting 37.5 g glucose (approximately 350 mL soft drink) interfered with pain modulation in pain-free adults with normal adiposity or with combined high adiposity and HbA1c levels. The interference was stronger alongside increasing central obesity, suggesting that controlling blood glucose and body fat mass might help preserve pain modulation.