Lack of cold pressor test-induced effect on visual-evoked potentials in migraine

Abstract

In patients with migraine, the various sensory stimulation modalities, including visual stimuli, invariably fail to elicit the normal response habituation. Whether this lack of habituation depends on abnormal activity in the sub-cortical structures responsible for processing incoming information as well as nociception and antinociception or on abnormal cortical excitability per se remains debateable. To find out whether inducing tonic pain in the hand by cold pressure test (CPT) alters the lack of visual-evoked potential (VEP) habituation in migraineurs without aura studied between attacks we recorded VEPs in 19 healthy subjects and in 12 migraine patients during four experimental conditions: baseline; no-pain (hand held in warm water, 25°C); pain (hand held in cold water, 2–4°C); and after-effects. We measured P100 amplitudes from six blocks of 100 sweeps, and assessed habituation from amplitude changes between the six sequential blocks. In healthy subjects, the CPT decreased block 1 VEP amplitude and abolished the normal VEP habituation (amplitude decrease to repeated stimulation) in patients with migraine studied between attacks; it left block 1 VEP amplitude and abnormal VEP habituation unchanged. These findings suggest that the interictal cortical dysfunction induced by migraine prevents the cortical changes induced by tonic painful stimulation both during pain and after pain ends. Because such cortical changes presumably reflect plasticity mechanisms in the stimulated cortex, our study suggests altered plasticity of sensory cortices in migraine. Whether this abnormality reflects abnormal functional activity in the subcortical structures subserving tonic pain activation remains conjectural.

Visual evoked potentials in migraine: Is the “neurophysiological hallmark” concept still valid?

“…Several previous VEP habituation studies seem underpowered compared to the present study (Coppola et al, 2011;Coppola et al, 2010b;Coppola et al, 2010a;Di Clemente et al, 2005;Fumal et al, 2006;Vigano et al, 2013). Significant findings in small studies with low power are less likely to reflect a true effect, and low power is associated with other sources of bias that may overestimate effect sizes (Button et al, 2013).…”

“…N70-P100 habituation slope was chosen as primary efficacy parameter because many previous studies only report N70-P100 and not P100-N145 amplitude habituation (Afra et al, 2000b;Coppola et al, 2007b;Coppola et al, 2011;Coppola et al, 2010a;Coppola et al, 2013b;Di Clemente et al, 2005;Ozkul and Bozlar, 2002). Neither N70-P100 nor P100-N145 habituation measures were significantly different between groups.…”

“…Several studies merely investigated how lack of VEP habituation in migraineurs is affected by interventions, such as coloured glass (Afra et al, 2000a), fluoxetine (Ozkul and Bozlar, 2002), repetitive transcranial magnetic stimulation (Bohotin et al, 2002;Fumal et al, 2006), cold pressor test (Coppola et al, 2010a), hyperventilation (Coppola et al, 2010b), light deprivation (Coppola et al, 2011) and direct current stimulation . Other studies investigated how lack of VEP habituation relates to other measures, such as personality tests (Wang et al, 1999), cortical auditory evoked potentials (Afra et al, 2000b) and nociceptive blink reflex (Di Clemente et al, 2005).…”

“…This was not confirmed in a study that applied 1.9 rps and 31' and 62' checks (Sand et al, 2009), nor in a study that applied 3.0 rps and 8' and 65' checks (Omland et al, 2013). However, most recent VEP habituation studies applied 14-16' checks (Bednar et al, 2014;Coppola et al, 2007b;Coppola et al, 2011;Coppola et al, 2010b;Coppola et al, 2010a;Coppola et al, 2013b). This check size may be preferable because habituation is more pronounced with smaller check sizes (e.g.…”

“…Most studies that reported lack of habituation in migraineurs were by one internationally collaborating group of authors (Afra et al, 1998;Afra et al, 2000b;Bohotin et al, 2002;Coppola et al, 2007b;Coppola et al, 2011;Coppola et al, 2010b;Coppola et al, 2010a;Coppola et al, 2013b;Di Clemente et al, 2005;Fumal et al, 2006;Schoenen et al, 1995;Vigano et al, 2013). As far as we know, lack of VEP habituation been independently confirmed in two studies (Bednar et al, 2014;Ozkul and Bozlar, 2002), while two other groups have not managed to reproduce this finding (Oelkers-Ax et al, 2005;Oelkers et al, 1999;Omland et al, 2013;Sand et al, 2008).…”