Systemic clonidine activates neurons of the dorsal horn, but not the locus ceruleus (A6) or the A7 area, after a formalin test: the importance of the dorsal horn in the antinociceptive effects of clonidine

Abstract

In order to clarify the principal site for the antinociceptive effects of clonidine, we investigated the nociceptive behavior and neural activity (c-fos staining) of the dorsal horn (DH), locus ceruleus (LC), and A7 area after a formalin test in normal saline- or clonidine-injected rats. Thirty-six rats were divided into 6 groups as follows: formalin test + saline (FS); formalin test + clonidine (1 mg.kg(-1)) (FC1); formalin test + clonidine (10 mg.kg(-1)) (FC10); saline (S); clonidine (1 mg.kg(-1)) (C1); and clonidine (10 mg.kg(-1)) (C10). Normal saline or clonidine was injected intraperitoneally 30 min before the formalin test. In the FS, FC1, and FC10 groups, 10% formalin was injected into the left rear paw. All rats were killed 2.5 h after normal saline or clonidine injection. Sections of the lumbar spinal cord, LC, and A7 area were processed for c-fos immunohistochemistry using the avidin-biotin peroxidase complex method. To evaluate the sedative effects of clonidine, we investigated the loss of righting reflex (LORR) for 90 min in 6 other rats as follows: clonidine (1 mg.kg(-1)) (n = 3) and clonidine (10 mg.kg(-1)) (n = 3). The FC10 group showed fewer nociceptive behaviors and higher c-fos expression in the DH, but not in the A7 area, as well as lower c-fos expression in the LC than rats in the FS and FC1 groups (P < 0.05). The C10 group showed lower c-fos expression in the LC than that of rats in the S and C1 groups (P < 0.05). No rats exhibited LORR. The antinociceptive effects of clonidine might be mediated primarily by neural activity in the DH.