Development of tactile allodynia and thermal hyperalgesia by intrathecally administered platelet-activating factor in mice.
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.
Morita
Katsuya
K
Department of Dental Pharmacology, Division of Integrated Medical Science, Hiroshima University Graduate School of Biomedical Sciences, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan Department of Dental Pharmacology, Field of Functional Physiology, Branch of Biophysiological Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikada, Okayama 700-8525, Japan Department of Pharmacology, Division of Clinical Pharmaceutical Sciences, Hiroshima University Graduate School of Biomedical Sciences, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan.
Morioka
Norimitsu
N
Abdin
Joynal
J
Kitayama
Shigeo
S
Nakata
Yoshihiro
Y
Dohi
Toshihiro
T
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement / Q000379:methods; D010972:Platelet Activating Factor / Q000008:administration & dosage* / Q000633:toxicity*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D014110:Touch / Q000187:drug effects / Q000502:physiology
D010972:Platelet Activating Factor