Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats.
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-N(6)-cyclopentyladenosine (100 nM) significantly decreased basal and evoked ATP release in DRG from naïve 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 O(2) consumption between control and neuropathic DRG. DRG ipsilateral to SNE consumed O(2) at a higher rate than control or contralateral DRG.


CONCLUSIONS
These data suggest that peripheral nerve entrapment increases DRG metabolism and ATP release, which in turn is modulated by increased A1R activation.
Matsuka
Yoshizo
Y
Division of Oral Biology & Medicine, School of Dentistry, University of California, Los Angeles, CA, USA. matsuka@md.okayama-u.ac.jp
Ono
Takeshi
T
Iwase
Hirotate
H
Mitrirattanakul
Somsak
S
Omoto
Kevin S
KS
Cho
Ting
T
Lam
Yan Yan N
YY
Snyder
Bradley
B
Spigelman
Igor
I
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption; D010523:Peripheral Nervous System Diseases / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries
D018047:Receptors, Purinergic P1; D011189:Potassium Chloride; D000255:Adenosine Triphosphate