scholarly journals Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Takahiro Masuda ◽  
Yui Ozono ◽  
Satsuki Mikuriya ◽  
Yuta Kohro ◽  
Hidetoshi Tozaki-Saitoh ◽  
...  
Pain ◽  
2019 ◽  
Vol 160 (5) ◽  
pp. 1082-1092 ◽  
Author(s):  
Zongqin Zhang ◽  
Xiaobao Ding ◽  
Zhiwei Zhou ◽  
Zhuang Qiu ◽  
Naihao Shi ◽  
...  

2015 ◽  
Vol 40 (5) ◽  
pp. 1000-1012 ◽  
Author(s):  
Yuya Yamamoto ◽  
Ryuji Terayama ◽  
Noriko Kishimoto ◽  
Kotaro Maruhama ◽  
Masahide Mizutani ◽  
...  

2015 ◽  
Vol 35 (44) ◽  
pp. 14943-14955 ◽  
Author(s):  
T.-B. Lin ◽  
C.-Y. Lai ◽  
M.-C. Hsieh ◽  
H.-H. Wang ◽  
J.-K. Cheng ◽  
...  

1997 ◽  
Vol 20 (3) ◽  
pp. 404-419 ◽  
Author(s):  
Terence J. Coderre ◽  
Joel Katz

This target article examines the clinical and experimental evidence for a role of peripheral and central hyperexcitability in persistent pain in four key areas: cutaneous hyperalgesia, referred pain, neuropathic pain, and postoperative pain. Each suggests that persistent pain depends not only on central sensitization, but also on inputs from damaged peripheral tissue. It is instructive to think of central sensitization as comprised of both an initial central sensitization and an ongoing central sensitization driven by inputs from peripheral sources. Each of these factors, initial sensitization, ongoing central sensitization, and inputs from peripheral sources, contributes to the net activity in dorsal horn neurons and thus influences the expression of persistent pain or hyperalgesia. Since each factor, peripheral inputs and central sensitization (initial or ongoing), can contribute to both the initiation and maintenance of persistent pain, therapies should target both peripheral and central sources of pathology.


2019 ◽  
Vol 20 (18) ◽  
pp. 4443 ◽  
Author(s):  
Yin ◽  
Hong ◽  
Phạm ◽  
Shin ◽  
Gwon ◽  
...  

Upon peripheral nerve injury, vesicular ATP is released from damaged primary afferent neurons. This extracellular ATP subsequently activates purinergic receptors of the spinal cord, which play a critical role in neuropathic pain. As an inhibitor of the vesicular nucleotide transporter (VNUT), Evans blue (EB) inhibits the vesicular storage and release of ATP in neurons. Thus, we tested whether EB could attenuate neuropathic pain behavior induced by spinal nerve ligation (SNL) in rats by targeting VNUT. An intrathecal injection of EB efficiently attenuated mechanical allodynia for five days in a dose-dependent manner and enhanced locomotive activity in an SNL rat model. Immunohistochemical analysis showed that EB was found in VNUT immunoreactivity on neurons in the dorsal root ganglion and the spinal dorsal horn. The level of ATP in cerebrospinal fluid in rats with SNL-induced neuropathic pain decreased upon administration of EB. Interestingly, EB blocked ATP release from neurons, but not glial cells in vitro. Eventually, the loss of ATP decreased microglial activity in the ipsilateral dorsal horn of the spinal cord, followed by a reduction in reactive oxygen species and proinflammatory mediators, such as interleukin (IL)-1β and IL-6. Finally, a similar analgesic effect of EB was demonstrated in rats with monoiodoacetate-induced osteoarthritis (OA) pain. Taken together, these data demonstrate that EB prevents ATP release in the spinal dorsal horn and reduces the ATP/purinergic receptor-induced activation of spinal microglia followed by a decline in algogenic substances, thereby relieving neuropathic pain in rats with SNL.


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