Evans Blue Reduces Neuropathic Pain Behavior by Inhibiting Spinal ATP Release
| Autor: | Nara Shin, Juhee Shin, Hyo Jung Shin, Yuhua Yin, Sun Yeul Lee, Jinpyo Hong, Dong Woon Kim, Do Hyeong Gwon, Thuỳ Linh Phạm, Wonhyung Lee, Hyeok Hee Kwon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Interleukin-1beta Pharmacology Catalysis Article Proinflammatory cytokine Inorganic Chemistry lcsh:Chemistry Rats Sprague-Dawley chemistry.chemical_compound Adenosine Triphosphate Dorsal root ganglion Ganglia Spinal medicine Animals Physical and Theoretical Chemistry Molecular Biology lcsh:QH301-705.5 Spectroscopy Evans Blue vesicular nucleotide transporter neuropathic pain Neurons Microglia Interleukin-6 Organic Chemistry Purinergic receptor General Medicine Spinal cord Evans blue Spine Computer Science Applications Rats ATP Disease Models Animal medicine.anatomical_structure chemistry lcsh:Biology (General) lcsh:QD1-999 spinal nerve ligation Peripheral nerve injury Neuropathic pain Neuralgia analgesic effect |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 20, Iss 18, p 4443 (2019) Volume 20 Issue 18 |
| ISSN: | 1422-0067 |
| Popis: | 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)-1&beta 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. |
| Databáze: | OpenAIRE |
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