Piezo2 in bladder-innervating sensory neurons contributes to regulation of contractile activity in cystitis

Overactivity of the urinary bladder constitutes one of the main symptoms in various lower urinary tract disorders and it significantly deteriorates quality of life. The crucial role of mechanotransduction in bladder-innervating unmyelinated C-type primary sensory nerve fibres in initiating the voiding reflex in the overactive bladder has been well established. However, the molecular identity of the mechanotransducer(s) in bladder-innervating C-type sensory neurons is still elusive. The mechanosensitive ion channel Piezo2 in primary sensory neurons has been implicated in various physiological and pathological functions including proprioception, the detection of low and high threshold mechanical stimuli in the skin, and the development of mechanical hypersensitivity in peripheral pathologies. Here, we investigated whether or not Piezo2 expressed in primary sensory neurons could contribute to bladder overactivity in cystitis. Characterisation of Piezo2 expression revealed that about 1/5 of primary sensory neurons express this ion channel and at least half of the Piezo2-expressing cells express various markers for unmyelinated C-type sensory neurons. Further, we found that Piezo2 is expressed predominantly in lamina I and II of the spinal cord, where C-type sensory neurons terminate. We disclosed that Piezo2 is expressed in sensory neuron terminals innervating peripheral tissues including the bladder wall and noxious but not innocuous pressure in the urinary bladder activates Piezo2-expressing primary sensory neurons. Finally, we show that instillation of GsMTx that blocks Piezo2 significantly reduces overactivity in the inflamed but not in the naive urinary bladder. Together these findings indicate that Piezo2 in bladder-innervating unmyelinated C-type neurons contributes to the detection of noxious pressure and regulation of contractile activity in cystitis.Overactivity of the urinary bladder constitutes one of the main symptoms in various lower urinary tract disorders and it significantly deteriorates quality of life. The crucial role of mechanotransduction in bladder-innervating unmyelinated C-type primary sensory nerve fibres in initiating the voiding reflex in the overactive bladder has been well established. However, the molecular identity of the mechanotransducer(s) in bladder-innervating C-type sensory neurons is still elusive. The mechanosensitive ion channel Piezo2 in primary sensory neurons has been implicated in various physiological and pathological functions including proprioception, the detection of low and high threshold mechanical stimuli in the skin, and the development of mechanical hypersensitivity in peripheral pathologies. Here, we investigated whether or not Piezo2 expressed in primary sensory neurons could contribute to bladder overactivity in cystitis. Characterisation of Piezo2 expression revealed that about 1/5 of primary sensory neurons express this ion channel and at least half of the Piezo2-expressing cells express various markers for unmyelinated C-type sensory neurons. Further, we found that Piezo2 is expressed predominantly in lamina I and II of the spinal cord, where C-type sensory neurons terminate. We disclosed that Piezo2 is expressed in sensory neuron terminals innervating peripheral tissues including the bladder wall and noxious but not innocuous pressure in the urinary bladder activates Piezo2-expressing primary sensory neurons. Finally, we show that instillation of GsMTx that blocks Piezo2 significantly reduces overactivity in the inflamed but not in the naive urinary bladder. Together these findings indicate that Piezo2 in bladder-innervating unmyelinated C-type neurons contributes to the detection of noxious pressure and regulation of contractile activity in cystitis

Localization of the spinal nucleus of accessory nerve in rat: a horseradish peroxidase study

The spinal nucleus of the accessory nerve (SNA) comprises the group of somata (perikarya) of motor neurons that supply the sternocleidomastoid and trapezius muscles. There are many conflicting views regarding the longitudinal extent and topography of the SNA, even in the same species, and these disagreements prompted the present investigation. Thirty Sprague–Dawley rats (15 males, 15 females) were used. The SNA was localized by retrograde axonal transport of horseradish peroxidase. Longitudinally, the SNA was found to be located in the caudal part (caudal 0.9–1.2 mm) of the medulla oblongata, the whole lengths of cervical spinal cord segments C1, C2, C3, C4, C5 and rostral fourth of C6. In the caudal part of the medulla oblongata, the SNA was represented by a group of perikarya of motor neurons lying immediately ventrolateral to the pyramidal fibres that were passing dorsolaterally after their decussation. In the spinal cord, the motor neuronal somata of the SNA were located in the dorsomedial and central columns at C1, in the dorsomedial, central and ventrolateral columns at C2 and in the ventrolateral column only at C3, C4, C5 and rostral quarter of C6. The perikarya of motor neurons supplying the sternocleidomastoid were located in the caudal part (caudal 0.9–1.2 mm) of the medulla oblongata ventrolateral to the pyramidal fibres that were passing dorsolaterally after their decussation. They were also located in the dorsomedial and central columns at C1, in the dorsomedial, central and ventrolateral columns at C2 and only in the ventrolateral column at the rostral three-quarters of C3. The perikarya of motor neurons supplying the trapezius muscle were located in the ventrolateral column only in the caudal three-quarters of C2, the whole lengths of C3, C4 and C5, and in the rostral quarter of C6