Characterization of the hypothalamic proopiomelanocortin gene and β-endorphin expression in the hypothalamic arcuate nucleus of mice elicited by inflammatory pain

We examined proopiomelanocortin (POMC) mRNA and β-endorphin expression in the hypothalamus of mice after various nociceptive stimuli. The time-course study (10 min, 30 min, 1 h, 2 h, and 10 h) showed that the POMC mRNA level significantly increases from 1 h after s.c. formalin injection and returns to the control level at 10 h. Intrathecal (i.t.) substance P (SP) injection also increases the hypothalamic POMC mRNA level from 1 h to 10 h. However, i.t. glutamate injection did not affect the hypothalamic POMC gene expression at all time points. We found that the POMC mRNA after s.c. formalin injection was located in the arcuate nucleus of the hypothalamus. In the same manner, β-endorphin immunoreactivity was also increased in the hypothalamic arcuate nucleus. The expression of phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2), phosphorylated calcium/calmodulin-dependent protein kinase-IIα (pCaMK-IIα) protein and phosphorylated IκB (pIκB) protein was increased by s.c. formalin injection at various time points. We also found that increased pERK1/2, pCaMKIIα and pIκB protein after s.c. formalin injection was mainly located in the arcuate nucleus of hypothalamus in which cells containing β-endorphin after s.c. formalin injection also express pERK1/2, pCaMK-IIα and pIκB immunoreactivity. In addition, formalin-induced POMC mRNA expression was significantly reduced by 10 min, pretreatment with i.c.v. PD98059 (mitogen-activated protein kinase (MAPK) pathways inhibitor; 6.6 μg) and KN93 (pCaMK-II inhibitor; 20 μg). In conclusion, POMC mRNA expression in the arcuate nucleus of the hypothalamus was increased by inflammatory pain stimuli, in which pERK1/2, pCaMK-IIα and NFκB may play an important role in the expression of the hypothalamic POMC gene and β-endorphin expression.