Ph.D. Defence by Morten Høgh

Pain modulation can be understood as a dynamic balance between facilitative and inhibitory pain mechanisms in the descending pathways. Common approaches to measuring the net-effect of descending pain modulation in humans are the conditioned pain modulation (CPM) paradigms. These paradigms study the effect of a painful conditioning stimulus on a test stimulus, compared to an unconditioned test stimulus; and can be categorised as a bottom-up (stimulus driven) mechanism. Conversely, pain can also be modulated via top-down (goal-oriented) modulatory mechanisms including expectation and attention. Social stress can be considered a hybrid between bottom-up (in relation to contextual allostasis) and top-down (influenced by perception) modulatory mechanisms. Bottom-up and top-down mechanisms are thought to share or have overlapping neurophysiological pathways.

This PhD project, comprising three studies, explored how repetition alone and in combination with stress or attention influences CPM in healthy men. Study-I showed that CPM-measurements could be repeated four times in 5-min bouts. Study-I also found the difference between the two test-stimuli in each bout (i.e. CPM effects and Control effects) were different; repeated test-stimuli (control session) led to cyclic increases in pain sensitivity with negative ‘control effects’ while positive CPM effects were found in the CPM-bouts. The study suggests that the temporal dynamic changes in painful stimuli involve non-linear effects and that the difference between control effects and CPM effects can provide a nuanced insight to the balance between descending facilitation and inhibition in healthy volunteers. In Study-II, CPM effects were found in all four sessions (before and after stress as well as before and after control). However, no significant changes in CPM effects from stress or control sessions could be found. In Study-III, it was found that application of Stroop to repeated test-stimuli, with or without conditioning, reduced pain sensitivity but not CPM effects. Study-III suggests that bottom-up and top-down modulatory mechanisms are independent of each other and that they may be seen as complementary rather than auxiliary mechanisms.

This PhD-project indicates that CPM is a reliable and stable paradigm to study bottom-up pain modulation. In addition, it was shown that repeated, unconditioned test-stimuli lead to negative, but cyclic, ‘control effects’ over time rather than to accumulated effects. Finally, this project finds that neither social stress, nor attention had any significant influence on CPM; and that attention can lead to analgesia independently of CPM.