title: Systemic administration of minocycline inhibits formalin-induced inflammatory pain in rat.
abstract: It has been demonstrated that spinal microglial activation is involved in formalin-induced pain and that minocycline, an inhibitor of microglial activation, attenuate behavioral hypersensitivity in neuropathic pain models. We investigated whether minocycline could have any anti-nociceptive effect on inflammatory pain, after intraperitonial administration of minocycline, 1 h before formalin (5%, 50 microl) injection into the plantar surface of rat hindpaw. Minocycline (15, 30, and 45 mg/kg) significantly decreased formalin-induced nociceptive behavior during phase II, but not during phase I. The enhancement in the number of c-Fos-positive cells in the L4-5 spinal dorsal horn (DH) and the magnitude of paw edema induced by formalin injection during phase II were significantly reduced by minocycline. Minocycline inhibited synaptic currents of substantia gelatinosa (SG) neurons in the spinal DH, whereas membrane electrical properties of dorsal root ganglion neurons were not affected by minocycline. Analysis with OX-42 antibody revealed the inhibitory effect of minocycline on microglial activation 3 days after formalin injection. These results demonstrate the anti-nociceptive effect of minocycline on formalin-induced inflammatory pain. In addition to the well-known inhibitory action of minocycline on microglial activation, the anti-edematous action in peripheral tissue, as well as the inhibition of synaptic transmission in SG neurons, is likely to be associated with the anti-nociceptive effect of minocycline.
authors.affiliation: Department of Physiology and Program in Molecular and Cellular Neuroscience, Seoul National University, 28-2 Yeongeon-Dong Chongno-Ku, Seoul 110-749, Korea.
authors.forename: Ik-Hyun
authors.initials: IH
authors.lastname: Cho
authors.forename: Young Min
authors.initials: YM
authors.lastname: Chung
authors.forename: Chul-Kyu
authors.initials: CK
authors.lastname: Park
authors.forename: Seong-Hae
authors.initials: SH
authors.lastname: Park
authors.forename: Haeyeong
authors.initials: H
authors.lastname: Lee
authors.forename: Hai Ying
authors.initials: HY
authors.lastname: Li
authors.forename: Donghoon
authors.initials: D
authors.lastname: Kim
authors.forename: Zheng Gen
authors.initials: ZG
authors.lastname: Piao
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Sung Joong
authors.initials: SJ
authors.lastname: Lee
authors.forename: Kyungpyo
authors.initials: K
authors.lastname: Park
authors.forename: Joong Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Jung
authors.forename: Seog Bae
authors.initials: SB
authors.lastname: Oh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004594:Electrophysiology; D005557:Formaldehyde / Q000633:toxicity*; D016762:Genes, fos / Q000187:drug effects; D006614:Hindlimb; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D008297:Male; D008911:Minocycline / Q000008:administration & dosage / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology
chemical_list: D000893:Anti-Inflammatory Agents; D005557:Formaldehyde; D008911:Minocycline