Effects of repeated conditioning pain modulation in healthy volunteers

Conditioned pain modulation (CPM) may be impaired in chronic pain patients compared with healthy subjects. The CPM-effect is the difference between pain sensitivity assessments (test-stimuli) with and without a painful conditioning stimulus. CPM has been extensively explored but effects of repeated CPM-effects and differences between repeated CPM assessments and comparable control conditions are less studied.

In 20 healthy men, four 5-min bouts with a test-stimulus in the beginning and midway were applied by cuff-algometry to the dominant leg. The 2nd test-stimulus in each bout was conditioned in parallel by a painful cuff pressure on the contralateral leg. A control-session was performed without conditioning. The conditioning intensity was 70% of the pressure-pain tolerance threshold (PTT) assessed at baseline. Pain detection threshold (PDT) was extracted from test-stimuli. CPM/Control-effects were calculated as second minus first test-stimulus, and netCPM-effects were calculated as the difference between CPM-effects and Control-effects.

Pain detection threshold increased in all four bouts (p < 0.02) compared to the unconditioned test-stimulus and compared to the 2nd test-stimulus in bout1, bout3 and bout4 of the control-session (p < 0.04). In the control-session, the 1st test-stimulus PDT increased from bout1 to bout2, bout3 and bout4 (p < 0.03). The netCPM-effect increased progressively over the four bouts (p = 0.03).

Conditioned pain modulation-effects were maintained over four consecutive bouts and in the control-session repeated pain thresholds assessments habituated more than in the CPM-session leading to an increase in netCPM-effect over the four bouts.

Conditioning pain modulation can be assessed in 5-min intervals by cuff algometry with a fixed conditioning stimulus. Without applying conditioning stimuli the pain sensitivity of test-stimuli habituated. As a consequence, it can be speculated that the conditioning stimulus may negate the temporal habituation effects during repeated sessions, whereas this may not be the case for unconditioned stimuli. Applying both conditioned and unconditioned repeated test-stimuli may be a way to assess different parts of the pain modulatory system, and a model for measuring a netCPM-effect, which could indicate a balance between habituation and sensitization, is proposed.