Effect of Intraperitoneal Nalbuphine-HCl on C-fos Expression in Rat Brain induced by Incisional Pain

Park, Chul Soo; Park, Chong Min; Joong, Ji Young

Abstract

BACKGROUND
Nalbuphine-HCl (Nubain(R)), an agonist-antagonist of kappa3 and mu receptors, has limited analgesic or sedative effects, and an effect ceiling. It is generally accepted that c-fos is a marker of neuronal activity and its expression is correlated with nerve pathways activated by nociceptive stimuli. The aim of this study was to examine the effect of nalbuphine-HCl (Nubain(R)) on c-fos expression in rat brain caused by incisional pain. METHODS: A 1.0 cm longitudinal incision was made through the skin, fascia, and muscle of the plantar aspect of the hind paw of male Sprague-Dawley rats (140-150 g). 2.87 mg/kg of nalbuphine-HCl was then injected intraperitoneally 1 hour before incision (pre-nubain group; N = 11) and 30 minutes after incision (post-nubain group; N = 10). Identical volumes of normal saline were injected 30 minutes after incision (control group; N = 14). Two hours later, c-fos protein expressions in the thalamus, hypothalamus, cerebral cortex, and amygdala were examined by immunohistochemistry using a specific antibody. RESULTS: In the thalamus, fewer c-fos positive cells were observed in the experimental group than in the control (P < 0.05). However, the numbers of positive cells in control, pre-nubain and post-nubain groups were 29.5 (9.0), 31.0 (19.5) and 20.5 (32.0) (median values and interquartile ranges), respectively, which were not significantly different. The experimental group (P < 0.05), also showed lower c-fos expressions in the hypothalamus; median values were 0.0 (19.0), 0.0 (11.3) and 0.0 (0.0) respectively, without significance. In the cerebral cortex, the pre-nubain group showed higher c-fos expression and the post-nubain group lower expression than the control (P < 0.05). The number of cells were 0.0 (0.0), 0.0 (9.0) and 0.0 (0.0) respectively, with no significant differences. In the amygdala, greater c-fos expression was observed in the experimental group (P < 0.05), the corresponding values were 2.5 (20.0), 8.4 (14.0) and 3.0 (12.0), again differences were not significant. CONCLUSIONS: These results suggest that nalbuphine-HCl protects from c-fos over-expression in thalamus which transmits pain to the cerebral cortex, but biphasic appearances were observed in cerebral cortex, these may be due to the dual effect of nalbuphine as an agonist and antagonist. Similar results were observed in the hypothalamus and amygdala, which transmit emotional stresses to the CNS. For more information on this issue, behavioral testing or PCR studies are needed.