• Cold pressor test (CPT);
  • Diffuse noxious inhibitory control (DNIC);
  • Gender;
  • Habituation;
  • Non-noxious inhibitory control (NNIC);
  • Quantitative sensory testing (QST)


Endogenous analgesia (EA) can be reflected by diffuse noxious inhibitory control (DNIC), non-noxious inhibitory control (NNIC) and habituation to repeated painful stimuli. However, the coexistence of these phenomena in a given individual and the degree to which various factors predict their magnitudes have not been fully investigated. Using experimental paradigms of DNIC, NNIC and habituation, the present study explored the relationships between – and the contribution factors to – the magnitude of EA exhibited by healthy volunteers (n = 191; 104 F, 87 M) exposed to these three experimental paradigms. Each subject was assigned to all three paradigms (DNIC-tested by co-administering repeated short painful heat stimuli and a conditioning tonic cold pain stimulation; NNIC – tested similarly with the exception of using a painless conditioning stimulation; habituation – tested by applying repeated painful heat stimuli only) in a random order. Pain intensities decreased from baseline in all three paradigms. However, DNIC produced significantly more pain reduction than the other two modes (RM-ANOVA). The magnitude of pain reduction of DNIC was found to be highly correlated with that of NNIC and habituation (r = 0.56, p < 0.001 for both correlations). A hierarchical regression analysis showed that baseline (p < 0.001) and conditioning pain scores (p = 0.043) predicted the magnitude of DNIC. A gender split analysis showed that conditioning pain scores served as a predictive factor for men only. Conclusions: Under these experimental conditions, different EA conditions seem to be related to each other. High initial pain intensities predict ‘effective’ DNIC and habituation, whereas intensity of the conditioning stimulus determines the magnitude of DNIC in men only.