Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats
Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats
复制标题
DOI：
10.1186/1744-8069-4-66
复制
发表时间：
2008-12-24
期刊：
影响因子：
3.3
通讯作者：
Spigelman, Igor
中科院分区：
文献类型：
--
作者：
Matsuka, Yoshizo;Ono, Takeshi;Spigelman, Igor
背景：腺苷三磷酸（ATP）在代谢中具有普遍的作用，并在组织损伤后的疼痛反应中起主要作用。我们研究了单侧坐骨神经卡压（SNE）诱导周围神经病变后大鼠背根神经节（DRG）基础和KCl诱发的ATP释放的变化。在神经病变诱导后15-21天，切除的同侧L4-L5 DRG与对侧或对照（幼稚）DRG相比显示显著升高的基础细胞外ATP水平。然而，KCl诱发的ATP释放不再观察到同侧DRG。我们假设，差异SNE对基础和诱发ATP释放的影响可能是由于细胞外ATP转化为腺苷，随后激活DRG神经元上的腺苷A1受体（A1 Rs）。添加选择性A1 R激动剂2-氯-N-6-环戊基腺苷（100 nM）显著降低了未处理大鼠DRG中的基础和诱发ATP释放，表明功能性A1 R激活。在SNE同侧DRG中，加入选择性A1 R拮抗剂8-环戊基-1，3-二丙基黄嘌呤（30 nM），进一步增加基础ATP水平，并缓解KCl诱发的ATP释放的阻滞，表明A1 R激活增加可减弱SNE同侧神经元中诱发的ATP释放。为了确定ATP释放的改变是否是DRG代谢改变的结果，我们比较了对照组和神经病性DRG之间的O-2消耗。SNE同侧DRG消耗O-2的速率高于对照组或对侧DRG。结论：这些数据表明，周围神经卡压增加DRG代谢和ATP释放，这反过来又通过增加A1 R激活来调节。
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 nave 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.Conclusion: These data suggest that peripheral nerve entrapment increases DRG metabolism and ATP release, which in turn is modulated by increased A1R activation.