Systemic administration of minocycline inhibits formalin-induced inflammatory pain in rat.
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.
Cho
Ik-Hyun
IH
Department of Physiology and Program in Molecular and Cellular Neuroscience, Seoul National University, 28-2 Yeongeon-Dong Chongno-Ku, Seoul 110-749, Korea.
Chung
Young Min
YM
Park
Chul-Kyu
CK
Park
Seong-Hae
SH
Lee
Haeyeong
H
Li
Hai Ying
HY
Kim
Donghoon
D
Piao
Zheng Gen
ZG
Choi
Se-Young
SY
Lee
Sung Joong
SJ
Park
Kyungpyo
K
Kim
Joong Soo
JS
Jung
Sung Jun
SJ
Oh
Seog Bae
SB
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
D000893:Anti-Inflammatory Agents; D005557:Formaldehyde; D008911:Minocycline