Injured nerve-derived COX2/PGE2 contributes to the maintenance of neuropathic pain in aged rats.
Neuropathic pain (NeP) is a debilitating disease afflicting mostly the aged population. Inflammatory responses in injured nerves play a pivotal role in the pathogenesis of NeP. Injured nerve derived cyclooxygenase 2/prostaglandin E2 (COX2/PGE2) contributes to the genesis of NeP at the early stage in young rats. Here we show that COX2/PGE2 is involved in the maintenance of NeP at a chronic stage in aged rats. Eighteen months after partial sciatic nerve ligation (PSNL), NeP remained prominent in aged rats. COX2 expressing macrophages and PGE2 levels were increased in injured nerves. PGE2 receptors (EP1 and EP4) and pain-related ion channel transient receptor potential vanilloid-1 (TRPV1) were increased in the ipsilateral dorsal root ganglion (DRG) neurons of aged PSNL rats. Perineural injection of a selective COX2 inhibitor NS-398 relieved NeP, reversed PSNL increased expression of EP1, EP4 and TRPV1 and suppressed the levels of pain-related peptide substance P and calcitonin gene-related peptide in DRG neurons. These data suggest that injured nerve-derived PGE2 contributes to the maintenance of NeP at the chronic stage in aged rats. Chronically facilitating the synthesis of pain-related molecules in nociceptive DRG neurons is a novel mechanism underpinning the contribution of PGE2.
Ma
Weiya
W
The Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada. Weiya.ma@douglas.mcgill.ca
Chabot
Jean-Guy
JG
Vercauteren
Freya
F
Quirion
Remi
R
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D002908:Chronic Disease; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology*; D005727:Ganglia, Spinal / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010525:Peripheral Nerves / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
D052246:Cyclooxygenase 2 Inhibitors; D018836:Inflammation Mediators; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone