Piezo channels are mechanosensitive ion channels. Piezo1 is primarily expressed in nonsensory tissues, whereas Piezo2 is predominantly found in sensory tissues, including dorsal root ganglion (DRG) neurons. However, a recent study demonstrated the intracellular calcium response to Yoda1, a selective Piezo1 agonist, in trigeminal ganglion (TG) neurons. Herein, we investigate the expression of Piezo1 mRNA and protein in mouse and human DRG neurons and the activation of Piezo1 via calcium influx by Yoda1. Yoda1 induces inward currents mainly in small- (<25 μm) and medium-sized (25–35 μm) mouse DRG neurons. The Yoda1-induced Ca2+ response is inhibited by cationic channel blocker, ruthenium red and cationic mechanosensitive channel blocker, GsMTx4. To confirm the specific inhibition of Piezo1, we performed an adeno-associated virus serotype 2/5 (AAV2/5)-mediated delivery of short hairpin RNA (shRNA) into mouse DRG neurons. AAV2/5 transfection downregulates piezo1 mRNA expression and reduces Ca2+ response by Yoda1. Piezo1 also shows physiological functions with transient receptor potential vanilloid 1 (TRPV1) in the same DRG neurons and is regulated by the activation of TRPV1 in mouse DRG sensory neurons. Overall, we found that Piezo1 has physiological functions in DRG neurons and that TRPV1 activation inhibits an inward current induced by Yoda1.
Chronic pain is a serious condition that occurs in the peripheral nervous system (PNS) and the central nervous system (CNS). It is caused by inflammation or nerve damage that induces the release of inflammatory mediators from immune cells and/or protein kinase activation in neuronal cells. Both nervous systems are closely linked; therefore, inflammation or nerve damage in the PNS can affect the CNS (central sensitization). In this process, nociceptive transient receptor potential (TRP) channel activation and expression are increased. As a result, nociceptive neurons are activated, and pain signals to the brain are amplified and prolonged. In other words, suppressing the onset of pain signals in the PNS can suppress pain signals to the CNS. Resolvins, endogenous lipid mediators generated during the resolution phase of acute inflammation, inhibit nociceptive TRP ion channels and alleviate chronic pain. This paper summarizes the effect of resolvins in chronic pain control and discusses future scientific perspectives. Further study on the effect of resolvins on neuropathic pain will expand the scope of pain research.
Migraine is a neurovascular disorder that affects approximately 12% of the global population. While its exact causes are still being studied, researchers believe that nociceptive neurons in the trigeminal ganglia play a key role in the pain signals of migraine. These nociceptive neurons innervate the intracranial meninges and convey pain signals from the meninges to the thalamus. Targeting nociceptive neurons is considered promising due to their accessibility and distinct molecular profile, which includes the expression of several transient receptor potential (TRP) channels. These channels have been linked to various pain conditions, including migraine. This review discusses the role and mechanisms of nociceptive neurons in migraine, the challenges of current anti-migraine drugs, and the evidence for well-studied and emerging TRP channels, particularly TRPC4, as novel targets for migraine prevention and treatment.
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