Waning of "Conditioned Pain Modulation": A Novel Expression of Subtle Pronociception in Migraine

Objective To assess the decay of the conditioned pain modulation (CPM) response along repeated applications as a possible expression of subtle pronociception in migraine. Background One of the most explored mechanisms underlying the pain modulation system is diffuse noxious inhibitory controls, which is measured psychophysically in the lab by the CPM paradigm. There are contradicting reports on CPM response in migraine, questioning whether migraineurs express pronociceptive pain modulation. Methods Migraineurs (n=26) and healthy controls (n=35), all females, underwent 3 stimulation series, consisting of repeated (1) test-stimulus (Ts) alone that was given first followed by (2) parallel CPM application (CPM-parallel), and (3) sequential CPM application (CPM-sequential), in which the Ts is delivered during or following the conditioning-stimulus, respectively. In all series, the Ts repeated 4 times (0-3). In the CPM series, repetition 0 consisted of the Ts-alone that was followed by 3 repetitions of the Ts with a conditioning-stimulus application. Results Although there was no difference between migraineurs and controls for the first CPM response in each series, we found waning of CPM-parallel efficiency along the series for migraineurs (P=.005 for third vs first CPM), but not for controls. Further, greater CPM waning in the CPM-sequential series was correlated with less reported extent of pain reduction by episodic medication (r=0.493, P=.028). Conclusions Migraineurs have subtle deficits in endogenous pain modulation which requires a more challenging test protocol than the commonly used single CPM. Waning of CPM response seems to reveal this pronociceptive state. The clinical relevance of the CPM waning effect is highlighted by its association with clinical parameters of migraine.