Involvement of primary afferent C-fibres in touch-evoked pain (allodynia) induced by prostaglandin E2.
Nociceptive primary afferents have the capacity to induce a state of increased excitability in dorsal horn neurons of the spinal cord or central sensitization causing thermal hyperalgesia and touch-evoked pain (allodynia). It is believed that primary afferent C-fibres become hypersensitive and induce hyperalgesia and that low-threshold Abeta-fibres are responsible for induction of allodynia, the mechanisms of which remain elusive. We previously showed that intrathecal administration of prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) induce allodynia in conscious mice. Here we demonstrated that selective elimination of C-fibres by neonatal capsaicin treatment resulted in the disappearance of allodynia induced by PGE2, but not that by PGF2alpha. PGE2-induced allodynia was not observed in N-methyl-D-aspartate (NMDA) receptor epsilon1 subunit knockout mice and was sensitive to morphine. In contrast, PGF2alpha-induced allodynia was not observed in NMDA epsilon4 subunit knockout mice and was insensitive to morphine. Furthermore, while PGF2alpha showed a capsaicin-insensitive feeble facilitatory action on evoked excitatory postsynaptic currents in dorsal horn neurons, PGE2 induced a long-lasting facilitation of evoked excitatory postsynaptic currents in a capsaicin-sensitive manner. Taken together, the present study demonstrates that there are two pathways for induction of allodynia and that capsaicin-sensitive C-fibres may participate in PGE2-induced allodynia.
Minami
T
T
Department of Anaesthesiology, Osaka Medical College, Takatsuki, Japan.
Okuda-Ashitaka
E
E
Hori
Y
Y
Sakuma
S
S
Sugimoto
T
T
Sakimura
K
K
Mishina
M
M
Ito
S
S
D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D015232:Dinoprostone; D004594:Electrophysiology; D006358:Hot Temperature; D006941:Hyperesthesia / Q000139:chemically induced* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout / Q000235:genetics; D009412:Nerve Fibers / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D010812:Physical Stimulation; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D014110:Touch / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D015232:Dinoprostone; D002211:Capsaicin