Preventing Extracellular Diffusion of Trigeminal Nitric Oxide Enhances Formalin-induced Orofacial Pain.
Nitric oxide (NO), a diffusible gas, is produced in the central nervous system, including the spinal cord dorsal horn and the trigeminal nucleus, the first central areas processing nociceptive information from periphery. In the spinal cord, it has been demonstrated that NO acts as pronociceptive or antinociceptive mediators, apparently in a concentration-dependent manner. However, the central role of NO in the trigeminal nucleus remains uncertain in support of processing the orofacial nociception. Thus, we here investigated the central role of NO in formalin (3%)-induced orofacial pain in rats by administering membrane-permeable or -impermeable inhibitors, relating to the NO signaling pathways, into intracisternal space. The intracisternal pretreatments with the NO synthase inhibitor L-NAME, the NO-sensitive guanylate cyclase inhibitor ODQ, and the protein kinase C inhibitor GF109203X, all of which are permeable to the cell membrane, significantly reduced the formalin-induced pain, whereas the membrane-impermeable NO scavenger PTIO significantly enhanced it, compared to vehicle controls. These data suggest that an overall effect of NO production in the trigeminal nucleus is pronociceptive, but NO extracellularly diffused out of its producing neurons would have an antinociceptive action.
Jung
Hwi-Seok
HS
School of Dentistry, Brain Korea 21, Brain Science and Engineering Institute, Kyungpook National University, Daegu 700-412, Korea.
Jeon
Hong-Bin
HB
Jeon
Ik-Sung
IS
Lee
Bum-Jun
BJ
Yoo
Hyun-Woo
HW
Ahn
Dong-Kuk
DK
Youn
Dong-Ho
DH