Nitric oxide and c-Jun N-terminal kinase are involved in the development of dark neurons induced by inflammatory pain.
Dark neurons, whose morphological characteristics are consistent with those of cells undergoing apoptosis, are generated in vivo as an acute or delayed consequence of several pathological situations and lesions. The present study was designed to evaluate whether inflammatory pain induced by injection of formalin to the rat hind paw lead to the formation of dark neurons in the dorsal horn of the lumbar spinal cord in rat. Since nitric oxide (NO) and c-Jun N-terminal Kinase (JNK) pathway are involved in the mechanisms of pain generation and degenerative neuronal alteration, their roles were also considered. The methods used spectrophotometrical analysis of the serum nitrite (metabolite of NO) and histological procedures for detection of dark neurons, following induction of inflammatory pain. According to the results, injection of formalin led to an increase of the serum nitrite level in both concentration and time-dependent manners. Visual inspections of the lumbar spinal cord sections showed that, on day 5, following chronic injections of 5% formalin, numbers of dark neurons were significantly increased. Acute and chronic administration of 1% or 2.5% formalin did not induce any remarkable neuronal alterations in the dorsal horn of the lumbar spinal cord. Daily intrathecal administration of quercetin (inhibitor of JNK pathway) 100 microg/rat, or 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO; NO scavenger) 30 mug/rat before injection of 5% formalin led to a reliable reduction in the number of dark neurons. These results indicate that induction of inflammatory pain for longer periods may result in a serious central disorder. Pretreatment with neutralizers or inhibitors of NO and JNK may exert a neuroprotective effect in this regard.
Hassanzadeh
Parichehr
P
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran.
Ahmadiani
Abolhassan
A
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007509:Irritants / Q000633:toxicity; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008161:Lumbosacral Region / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D020671:Posterior Horn Cells / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
D007509:Irritants; D009573:Nitrites; D005557:Formaldehyde; D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases