Hassanzadeh P, Ahmadiani A. Role of nitric oxide and Jun N-terminal kinase in the development of dark neurons in the dorsal horn of the spinal cord following induction of inflammatory pain . Physiol Pharmacol 2007; 11 (1) :1-9
URL:
http://ppj.phypha.ir/article-1-374-en.html
Abstract: (16409 Views)
Introduction: Dark neurons which their morphological characteristics are consistent with those of cells undergoing
apoptosis, are generated as an acute or delayed consequence of several pathological situations. The present study was
designed to evaluate whether inflammatory pain regarding the role of NO and JNK lead to the formation of dark
neurons in the dorsal horn of the lumbar spinal cord in rats.
Methods: Acute or chronic inflammatory pain was induced by intraplantar injection of 1%, 2.5% or 5% formalin in
male Wistar rats weighing 250-300 g (n=7). Spectrophotometrical analysis of the serum nitrite (metabolite of NO) and
histological procedures for detection of dark neurons were performed at definite time intervals. Pretreatment with
celecoxib 10, 20 or 40 mg/kg/i.p. quercetin 40 or 100 μg/rat/i.t. as an inhibitor of JNK pathway, and PTIO 20 or 30
μg/rat/i.t, as NO scavenger, were performed to investigate the role of NO and JNK.
Results: Injection of formalin led to the increase of the serum nitrite in the concentration and time-dependent
manners. The effect of 5% formalin was significantly eminent which was blocked by celecoxib 40 mg/kg. Visual
inspections of the spinal cord sections showed that on day 5, following chronic injections of 5% formalin, numbers of
dark neurons were significantly increased in the lumbar dorsal horn. Acute and chronic administration of other
concentrations of formalin did not induce any remarkable dark phenotype. Injections of celecoxib 40 mg/kg, quercetin
100 μg/rat/i.t. or PTIO 30 μg/rat/i.t. before each injection of 5% formalin, led to a reliable reduction of dark neurons.
Conclusion: The results showed that the intensity and duration of the inflammatory pain play a major role in its
peripheral and central developed disorders. According to the role of NO and JNK it seems that administration of their
inhibitors, or an appropriate dose of celecoxib may exert a protective effect against the aforementioned consequences.