Abstract
Background and Purpose : Injured peripheral tissue often becomes neuroplastic due to excessive
release of spinal amino acids that interact with neuronal receptors in the posterior horn of the
spinal cord. In this study, pain modulation by inhibitors through inactivation of glial cells associated
with modification of synaptic transmission in the spinal cord was examined in a rat inflammatory
pain mode l.
Methods: Male SD rats implanted with an intrathecal catheter (PE-10) were subjected to mustard
oil (MO)-induced hyperalgesia. Pain in the early stage was assessed by counting the spontaneous
flinches per minute after MO infusion and observing the pain reaction (flinching). The
reaction latency (PWL, sec) to thermal stimulus of the sole was measured 24 hours later to
evaluate the reaction to pain. A COX-II inhibitor (SC236), a p38-MAPK inhibitor (SB203580), a
microglial deactivator (m.inocycline), and a BDNF receptor inhibitor (K252a) were individually
administered i.t. before MO infusion. Flinching behavior and PWL after each treatment were
compared with those in an untreated group.
Result: F linching oft heu ntreated ratsr eached ap eak at3 0 minutes after MOi nfusion, and then
decreased and almost disappeared after eight hours. Administration of SC236, SB203580, minocycline,
and K252a reduced the flinching by 40-60 %. Discussion : Our results indicate the involvement of activation of microglia in response to p38-
MAPK activation, which significantly modifies synaptic transmission in the spinal cord nerve system
in the early stage of development in a rat inflammatory pain model. This suggests that microglia
may be activated in response to inflammation, along with activation of COX-II and p38-
MAPK and release of BDNF in the early stage of development of intractable pain after tissue
damage. The antibacterial agent, minocycline, and BDNF inhibitors may be useful for treatment
of such acute-phase inflammatory pain, in addition to use of conventional anti-inflammatory
agents.
https://ror.org/03bwzch55 
