Altered mitochondrial ATP synthase expression in the rat dorsal root ganglion after sciatic nerve injury and analgesic effects of intrathecal ATP.
Mitochondrial ATP synthase has multiple interdependent biological functions in neurons. Among them, ATP generation and regulation are the most important. The present study investigated whether the expression of mitochondrial ATP synthase correlates with symptoms of neuropathic pain in adult rats after axotomy, and whether intrathecal ATP administration is therapeutic in these neuropathic rats. Male Sprague-Dawley rats received left sciatic nerve transection (axotomy) and were randomly designated to a control (sham-operated) group, a neuropathic pain group (axotomy), a neuropathic pain and intrathecal sterile saline group, and a neuropathic pain and intrathecal ATP group. The thermal and mechanical sensitivity tests were performed at 1, 3, 5, and 7 days after axotomy. Left L4-L5 dorsal root ganglions (DRGs) were harvested to assess mitochondrial ATP synthase by immunoblotting and immunohistochemistry. After nerve injury, the expression of mitochondrial ATP synthase was decreased in protein extracts and was found mainly in C-fiber and A-δ fiber neurons of the DRGs. The decreased expression of mitochondrial ATP synthase and its subcellular localization were related to thermal and mechanical hyperalgesia. Administration of intrathecal ATP significantly attenuated thermal and mechanical hypersensitivity throughout the experimental period, which suggests its potential role in the treatment of neuropathic pain.
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123 Dapi Rd., Niaosong District, Kaohsiung, 833, Taiwan (R.O.C.).
Kuan-Hung
KH
Chen
Chung-Ren
CR
Lin
Jiin-Tsuey
JT
Cheng
Jen-Kun
JK
Cheng
Wen-Tzu
WT
Liao
Chien-Hui
CH
Yang
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D019771:Axotomy; D048429:Cell Size / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D059225:Nociception / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology
D000700:Analgesics; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases