The Molecular Signatures of Acute-immobilization-induced Antinociception and Chronic-immobilization-induced Antinociceptive Tolerance

Feng, Jing Hui; Lee, Hee Jung; Suh, Hong Won

Abstract

In the present study, the productions of antinociception induced by acute and chronic immobilization stress were compared in several animal pain models. In the acute immobilization stress model (up to 1 hr immobilization), the antinociception was produced in writhing, tail-flick, and formalin-induced pain models. In chronic immobilization stress experiment, the mouse was enforced into immobilization for 1 hr/day for 3, 7, or 14 days, then analgesic tests were performed. The antinociceptive effect was gradually reduced after 3, 7 and 14 days of immobilization stress. To delineate the molecular mechanism involved in the antinociceptive tolerance development in the chronic stress model, the expressions of some signal molecules in dorsal root ganglia (DRG), spinal cord, hippocampus, and the hypothalamus were observed in acute and chronic immobilization models. The COX-2 in DRG, p-JNK, p-AMPKÎ±1, and p-mTOR in the spinal cord, p-P38 in the hippocampus, and p-AMPKÎ±1 in the hypothalamus were elevated in acute immobilization stress, but were reduced gradually after 3, 7 and 14 days of immobilization stress. Our results suggest that the chronic immobilization stress causes development of tolerance to the antinociception induced by acute immobilization stress. In addition, the COX-2 in DRG, p-JNK, p-AMPKÎ±1, and p-mTOR in the spinal cord, p-P38 in the hippocampus, and p-AMPKÎ±1 in the hypothalamus may play important roles in the regulation of antinociception induced by acute immobilization stress and the tolerance development induced by chronic immobilization stress.