Acute pain induces insulin resistance in humans

Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin.

Ten healthy male volunteers underwent two randomly sequenced hyperinsulinemic-euglycemic (insulin infusion rate, 0.6 mU x kg(-1) x min(-1) for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0-10, just before the clamp procedure (study P). In the other study, no pain was inflicted (study C).

Pain reduced whole-body insulin-stimulated glucose uptake from 6.37+/-1.87 mg x kg(-1) x min(-1) (mean +/- SD) in study C to 4.97+/-1.38 mg x kg(-1) x min(-1) in study P (P < 0.01) because of a decrease in nonoxidative glucose disposal, as determined by indirect calorimetry (2.47+/-0.88 mg x kg(-1) x min(-1) in study P vs. 3.41+/-1.03 mg x kg(-1) x min(-1) in study C; P < 0.05). Differences in glucose oxidation rates were not statistically significant. The suppression of isotopically determined endogenous glucose output during hyperinsulinemia tended to be decreased after pain (1.67+/-0.48 mg x kg(-1) x min(-1) in study P vs. 2.04+/-0.45 mg x kg(-1) x min(-1) in study C; P = 0.06). Pain elicited a twofold to threefold increase in serum cortisol (P < 0.01), plasma epinephrine (P < 0.05), and serum free fatty acids (P < 0.05). Similarly, circulating concentrations of glucagon and growth hormone tended to increase during pain.

Acute severe pain decreases insulin sensitivity, primarily by affecting nonoxidative glucose metabolism. It is conceivable that the counterregulatory hormonal response plays an important role. This may indicate that pain relief in stress states is important for maintenance of normal glucose metabolism.