Dopamine D2/D3 Imbalance During Migraine Attack and Allodynia In Vivo

Objectives: To evaluate in vivo the dynamics of endogenous dopamine (DA) neurotransmission in migraineurs before and during a migraine ictus with allodynia.
Methods: We examined eight episodic migraineurs and eight age- and gender-matched healthy controls using PET with [¹¹C]raclopride (selective radiotracer for DA D2/D3 receptors). The measure of striatal uptake of [¹¹C]raclopride, non-displaceable binding potential (BP_ND), would increase when there was a reduction in endogenous DA release. The opposite is true for a decrease in [¹¹C]raclopride BP_ND. Patients were scanned twice: one PET session was during a spontaneous migraine ictus at rest, followed by a sustained thermal pain threshold (STPT) challenge on the trigeminal region, eliciting an allodynia experience; another was during interictal phase.
Results: Striatal BP_ND of [¹¹C]raclopride in migraineurs did not differ from controls. However, we found a significant increase in [¹¹C]raclopride BP_ND (decreased DA release) in the striatum region of migraineurs during both headache attack (left Putamen p<0.001, right Caudate p=0.001, and right Putamen p=0.001) and allodynia experience (left Putamen p<0.001, left Caudate p<0.001, and right Insula p<0.001) compared with the interictal phase. Furthermore, ictal changes in [¹¹C]raclopride BP_ND levels in migraineurs at rest were positively correlated with the chronicity of migraine attacks (p=0.047), and the frequency of attacks (p=0.016) during the allodynia experience (STPT).

Conclusions: Migraine has been associated with a higher prevalence of dopamine-deficient disorders including Parkinson’s disease and restless legs syndrome. Our findings demonstrate for the first time in vivo that there is an increased striatal uptake of [¹¹C]raclopride during the headache attack and allodynia, which indicates an imbalance in ictal endogenous DA release in migraineurs. Moreover, the longer the history and recurrence of migraine attacks, the lower the ictal endogenous DA release.