scholarly journals Piezo2 mechanosensitive ion channel is located to sensory neurons and non-neuronal cells in rat peripheral sensory pathway: implications in pain

2021 ◽  
Author(s):  
Seung Min Shin ◽  
Francie Moehring ◽  
Brandon Itson-Zoske ◽  
Fan Fan ◽  
Cheryl L. Stucky ◽  
...  

AbstractPiezo2 mechanotransduction channel is a crucial mediator of sensory neurons for sensing and transducing touch, vibration, and proprioception. We here characterized Piezo2 expression and cell specificity in rat peripheral sensory pathway using a validated Piezo2 antibody. Immunohistochemistry using this antibody revealed Piezo2 expression in pan primary sensory neurons (PSNs) of dorsal rood ganglia (DRG) in naïve rats, which was actively transported along afferent axons to both central presynaptic terminals innervating the spinal dorsal horn (DH) and peripheral afferent terminals in skin. Piezo2 immunoreactivity (IR) was also detected in the postsynaptic neurons of the DH and in the motor neurons of the ventral horn, but not in spinal GFAP- and Iba1-positive glia. Notably, Piezo2-IR was clearly identified in peripheral non-neuronal cells, including perineuronal glia, Schwann cells in the sciatic nerve and surrounding cutaneous afferent endings, as well as in skin epidermal Merkel cells and melanocytes. Immunoblots showed increased Piezo2 in DRG ipsilateral to plantar injection of complete Freund’s adjuvant (CFA), and immunostaining revealed increased Piezo2-IR intensity in the DH ipsilateral to CFA injection. This elevation of DH Piezo2-IR was also evident in various neuropathic pain models and monosodium iodoacetate (MIA) knee osteoarthritis (OA) pain model, compared to controls. We conclude that 1) the pan neuronal profile of Piezo2 expression suggests that Piezo2 may function extend beyond simply touch/proprioception mediated by large-sized low-threshold mechanosensitive PSNs, 2) Piezo2 may have functional roles involving sensory processing in spinal cord, Schwann cells, and skin melanocytes, and 3) aberrant Piezo2 expression may contribute pain pathogenesis.

2021 ◽  
Author(s):  
Seung Min Shin ◽  
Brandon Itson-Zoske ◽  
Fan Fan ◽  
Cheryl L. Stucky ◽  
Quinn H. Hogan ◽  
...  

AbstractHere, we present evidence showing Piezo1 expression in the primary sensory neurons (PSNs) and non-neuronal cells of rat peripheral nervous system. Using a knockdown/knockout validated antibody, we detected Piezo1 immunoreactivity (IR) in ∼80% of PSNs of rat dorsal root ganglia (DRG) with higher IR density in the small- and medium-sized neurons, and within axons extending to both central presynaptic terminals innervating to the spinal dorsal horn and peripheral cutaneous sensory terminals in the skin. Piezo-IR was clearly identified in DRG perineuronal glia, including satellite glial cells (SGCs) and non-myelinating Schwann cells; in sciatic nerve Schwann cells surrounding the axons and cutaneous afferent endings; and in skin epidermal Merkel cells and melanocytes. Neuronal and non-neuronal Piezo1 channels were functional, since various cells (dissociated PSNs and SGCs from DRGs, isolated Schwann cells, and primary human melanocytes) exhibited a robust response to Piezo1 agonist Yoda1 by an increase of intracellular Ca2+ concentration ([Ca2+]i). These responses were abolished by Piezo1 antagonist GsMTx4. Immunoblots showed elevated Piezo1 protein in DRG proximal to peripheral nerve injury-induced painful neuropathy, while PSNs and SGCs from rats with neuropathic pain showed greater Yuda1-evoked elevation of [Ca2+]i and an increased frequency of cells responding to Yoda1, compared to controls. Ipsilateral sciatic nerve application of GsMTx4 alleviated mechanical hypersensitivity following nerve injury. Overall, our data show that Piezo1 is widely expressed by the neuronal and non-neuronal cells in the peripheral sensory pathways and that painful nerve injury is associated with activation of Piezo1 in PSNs and peripheral glia cells.


Pain ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Seung Min Shin ◽  
Francie Moehring ◽  
Brandon Itson-Zoske ◽  
Fan Fan ◽  
Cheryl L. Stucky ◽  
...  

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 359-369 ◽  
Author(s):  
T. Becker ◽  
A.J. Berliner ◽  
M.N. Nitabach ◽  
W.B. Gan ◽  
E.R. Macagno

During a critical period in leech embryogenesis, the sex nerves that connect the 5th and 6th midbody ganglia (MG5 and MG6) to the primordium of the male sexual organ carry a spatially localized signal that induces the birth of several hundred neurons specific to these ganglia. We examined particular cellular elements (afferents, efferents, non-neuronal components) within these nerves as potential conveyors of the inductive signal. We show that axons of peripheral sensory neurons in the male genitalia travel along the sex nerves and into MG5 and MG6, but reach the CNS after the critical period has elapsed and cannot, therefore, be involved in the induction. Of the six sex nerves, four contain non-neuronal cells that span the entire distance between the male genitalia and the sex ganglia. However, when male genitalia were transplanted to ectopic locations close to MG6, induction occurred frequently but only in MG6, mediated by ectopic nerves that do not contain these cells. Thus, non-neuronal cells specific to the normal sex nerves are not necessary for induction. In addition, dye injections into the target during the critical period failed to reveal migrating cells in the sex nerves that could convey the inductive signal to the CNS. Finally, we show that 11 pairs of central neurons in each ganglion project to the male organ early during the critical period. In the adult, at least 3 additional pairs of neurons in MG6 also innervate this target. We conclude that the only components of the sex nerves that connect the sex ganglia to the target during the critical period that could be associated with induced central mitogenesis are the axons of central neurons that innervate the male genitalia.


Neuroscience ◽  
2010 ◽  
Vol 169 (1) ◽  
pp. 449-454 ◽  
Author(s):  
C. König ◽  
O. Gavrilova-Ruch ◽  
G. Segond von Banchet ◽  
R. Bauer ◽  
M. Grün ◽  
...  

Science ◽  
1957 ◽  
Vol 126 (3267) ◽  
pp. 256-257 ◽  
Author(s):  
B. LIBET

Pain ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 2364-2372 ◽  
Author(s):  
Kalina Szteyn ◽  
Matthew P. Rowan ◽  
Ruben Gomez ◽  
Junhui Du ◽  
Susan M. Carlton ◽  
...  

2000 ◽  
Vol 203 (3) ◽  
pp. 435-445
Author(s):  
M. Wildman

The position of the coxal segment of the locust hind leg relative to the thorax is monitored by a variety of proprioceptors, including three chordotonal organs and a myochordotonal organ. The sensory neurons of two of these proprioceptors, the posterior joint chordotonal organ (pjCO) and the myochordotonal organ (MCO), have axons in the purely sensory metathoracic nerve 2C (N2C). The connections made by these afferents with metathoracic motor neurons innervating thoraco-coxal and wing muscles were investigated by electrical stimulation of N2C and by matching postsynaptic potentials in motor neurons with afferent spikes in N2C. Stretch applied to the anterior rotator muscle of the coxa (M121), with which the MCO is associated, evoked sensory spikes in N2C. Some of the MCO afferent neurons make direct excitatory chemical synaptic connections with motor neurons innervating the thoraco-coxal muscles M121, M126 and M125. Parallel polysynaptic pathways via unidentified interneurons also exist between MCO afferents and these motor neurons. Connections with the common inhibitor 1 neuron and motor neurons innervating the thoraco-coxal muscles M123/4 and wing muscles M113 and M127 are polysynaptic. Afferents of the pjCO also make polysynaptic connections with motor neurons innervating thoraco-coxal and wing muscles, but no evidence for monosynaptic pathways was found.


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