Publication: Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats.
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2008
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Mahidol University
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Matsuka Y, Ono T, Iwase H, Mitrirattanakul S, Omoto KS, Cho T, et al. Altered ATP release and metabolism in dorsal root ganglia of
neuropathic rats. Molecular Pain. 2008; 4:66.
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Somsak Mitrirattanakul, Yoshizo Matsuka, Takeshi Ono, Hirotate Iwase, Kevin S Omoto, Ting Cho, Yan Yan N Lam, Bradley Snyder, สมศักดิ์ ไมตรีรัตนะกุล (2008). Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats.. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/929.
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Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats.
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Abstract
Background: Adenosine 5'-triphosphate (ATP) has a ubiquitous role in metabolism and a major
role in pain responses after tissue injury. We investigated the changes in basal and KCl-evoked ATP
release from rat dorsal root ganglia (DRG) after peripheral neuropathy induction by unilateral
sciatic nerve entrapment (SNE).
Results: After SNE, rats develop long-lasting decreases in ipsilateral hindpaw withdrawal
thresholds to mechanical and thermal stimulation. At 15–21 days after neuropathy induction,
excised ipsilateral L4-L5 DRG display significantly elevated basal extracellular ATP levels compared
to contralateral or control (naive) DRG. However, KCl-evoked ATP release is no longer observed
in ipsilateral DRG. We hypothesized that the differential SNE effects on basal and evoked ATP
release could result from the conversion of extracellular ATP to adenosine with subsequent
activation of adenosine A1 receptors (A1Rs) on DRG neurons. Adding the selective A1R agonist,
2-chloro-N6-cyclopentyladenosine (100 nM) significantly decreased basal and evoked ATP release
in DRG from na?ve rats, indicating functional A1R activation. In DRG ipsilateral to SNE, adding a
selective A1R antagonist, 8-cyclopentyl-1,3-dipropylxanthine (30 nM), further increased basal ATP
levels and relieved the blockade of KCl-evoked ATP release suggesting that increased A1R
activation attenuates evoked ATP release in neurons ipsilateral to SNE. To determine if altered
ATP release was a consequence of altered DRG metabolism we compared O2 consumption
between control and neuropathic DRG. DRG ipsilateral to SNE consumed O2 at a higher rate than
control or contralateral DRG.
Conclusion: These data suggest that peripheral nerve entrapment increases DRG metabolism and ATP release, which in turn is modulated by increased A1R activation.