Platelet-activating factor (PAF) is a potent inflammatory
lipid mediator in peripheral tissues. However, its role in mediation of nociception in central nervous system is unknown. In the present study, whether PAF plays some role in
pain transduction in the spinal cord was studied in mice.
Intrathecal injection of PAF induced tactile
pain,
tactile allodynia at as low as 10 fg to 1 pg with a peak response at 100 fg, while
lyso-PAF was without effect in the range of doses.
Tactile allodynia induced by PAF was blocked by a PAF receptor antagonists,
TCV-309,
WEB 2086 and
BN 50739. The expression of PAF receptor
mRNA by RT-PCR was observed in DRG and spinal cord in mice.
ATP P2X receptor antagonists, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic
acid and 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5-triphosphate,
NMDA receptor antagonist,
MK 801 and
nitric oxide synthetase inhibitor,
7-nitroindazole blocked the PAF-induced
tactile allodynia. PAF-induced
tactile allodynia and
thermal hyperalgesia disappeared in neonatally
capsaicin-treated adult mice, while
tactile allodynia but not
thermal hyperalgesia induced by intrathecally injected
alpha,beta-methylene ATP, a P2X receptor agonist, was
capsaicin-insensitive. The present study demonstrated that PAF is a potent inducer of
tactile allodynia and
thermal hyperalgesia at the level of the spinal cord. PAF-evoked
tactile allodynia is suggested to be mediated by
ATP and the following
NMDA and NO cascade through
capsaicin-sensitive fiber, different from exogenously injected
alpha,beta-methylene ATP which is insensitive to
capsaicin treatment.