The Role of TRP Channels in Migraine

Abstract

TRP channels are members of a large family of non-selective cation channels. The family which numbers over 30 is classified into 6 groups based on amino acid sequence homology. TRP channels are distributed in many peripheral tissues as well as central and peripheral nervous system. These channels are important in sensing a wide range of chemical and physical stimuli. Several TRP channels, including TRPV1 and TRPA1 are important in pain transduction pathways. This review will focus on the function of TRP channels in the trigeminovascular system and other anatomical regions which are relevant to migraine. We will discuss the possible role of TRP channels in migraine, including the potential role of TRPV1 in the hypersensitivity and allodynia frequently observed in migraine patients. We will review the status of TRP channel drugs in migraine therapeutics. We will also discuss the possible roles of TRP channels in triggering migraine attacks, a process which is not well-understood.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…This concept has gained strong experimental support by the efficacy of CGRP antagonists in clinical trials (Olesen and Ashina, 2011;Salvatore and Kane, 2011). TRP channels are promising targets in migraine (see Nassini et al, 2010aNassini et al, , 2013Dux et al, 2012;Oxford and Hurley, 2013), both in preventing attacks (e.g., TRPA1 is a well established target for air pollutants and odors) and in relieving headache (TRPV1 is thought to play a central role in neurogenic inflammation including CGRP release).…”

“…Importantly, these TRPA1 agonists induce CGRP release from dural tissue and stimulate meningeal vasodilatation (Kunkler et al, 2011). There is good evidence that activation by irritants of TRPA1 receptors at trigeminal nerve terminals in the nasal mucosa and subsequent activation of the trigeminovascular system play an important role in air pollution-induced headache (see Nassini et al, 2013;Oxford and Hurley, 2013). Studies on the potential role of TRPA1 in migraine are, however, still in their infancy (reviewed in Benemei et al, 2013).…”

TRPA1 deficiency is protective in cuprizone-induced demyelination-A new target against oligodendrocyte apoptosis

“…Cold and mechanical stimuli also gate the TRPA1 (Andersson et al, 2008;Story et al, 2003), which is predominantly expressed in peptidergic primary afferent somatosensory neurons in dorsal root (DRG), trigeminal (TRG), and nodose ganglia (NG) (Nagata et al, 2005). However, there is accumulating evidence that TRPA1 receptors have functional roles in asthma (Grace et al, 2014), migraine (Oxford and Hurley, 2013), colitis (Engel et al, 2011), itch (Wilson et al, 2011), andcystitis (DeBerry et al, 2014). It has a well-known function in pain sensation (Bautista et al, 2006).…”

“…It has a well-known function in pain sensation (Bautista et al, 2006). However, there is accumulating evidence that TRPA1 receptors have functional roles in asthma (Grace et al, 2014), migraine (Oxford and Hurley, 2013), colitis (Engel et al, 2011), itch (Wilson et al, 2011), andcystitis (DeBerry et al, 2014). In cultured astrocytes near-membrane local spontaneous [Ca 21 ] i transients were inhibited by the TRP channel antagonist HC-030031 or anti-TRP silencing RNA.…”

Genes and primary headaches: discovering new potential therapeutic targets

“…Recently, the transient receptor potential (TRP) channels gained increased interest for their potential involvement in primary headaches [61,62]. There are at least 30 members of the mammalian TRP family, which are coded by several, different genes.…”