Migraine and Two-Pore-Domain Potassium Channels

Abstract

Migraine is a common, disabling neurological disorder with a genetic, environmental, and hormonal component with an annual prevalence estimated at ~15%. It is characterized by attacks of severe, usually unilateral and throbbing headache, and can be accompanied by nausea, vomiting, and photophobia. Migraine is clinically divided into two main subtypes: migraine with aura, when it is preceded by transient neurological disturbances due to cortical spreading depression (CSD), and migraine without aura. Activation and sensitization of trigeminal sensory neurons, leading to the release of pro-inflammatory peptides, is likely a key component in headache pain initiation and transmission in migraine. In the present review, we will focus on the function of two-pore-domain potassium (K2P) channels, which control trigeminal sensory neuron excitability and their potential interest for developing new drugs to treat migraine.

What Is the Role of 2-Pore Domain Potassium Channels (K2P) in Pain?

“…44 This indicates the involvement of TREK channels in addition to TRESK in the development of pain in migraine. 16,20 This is supported by the finding that activation of TREK1 and TREK2 inhibited trigeminal ganglion neuron firing sufficiently to reverse the migraine-like phenotype induced by nitric oxide donors in rodents. 93 In addition to TREK and TRESK channels, primary afferents express TWIK1, TWIK2, TASK1, TASK3, THIK1, and THIK2 (K2P12) channels.…”

“…14 Given their importance in pain modulation, voltage-gated K + channels (K v ) and 2-pore domain K + channels (K2P) are potential targets for designing novel analgesic compounds. 6,[14][15][16][17] This review will focus on K2P channels, which are multimodal sensors that may have an important role in several pain disorders, including neuropathic pain and migraine 6,[15][16][17][18][19][20]…”

Melatonin Abates TMJOA Chronic Pain by MT2R in Trigeminal Ganglion Neurons

“…These results indicate that MT decreases [Ca 2+ ] i in primary sensory neurons by MT 2 R and hence the excitability of these neurons. However, growing evidence supports that intracellular Na + and K + participate in the pathogenesis of pain (Estacion et al 2015; Verkest et al 2021). Although we could not exclude the possibility that MT/MT 2 R may also regulate these ion signals in MIA-induced TMJOA chronic pain, it is reasonable to believe that Ca 2+ is crucial for MT to relieve TMJOA chronic pain, as recent studies have reported that MT inhibited Ca 2+ currents but not Na + and K + currents in TG neurons (Zhang et al 2018).…”