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 A beta-fibres are responsible for induction of allodynia, the mechanisms of which remain elusive. We previously showed that intrathecal administration of prostaglandin E-2 (PGE(2)) and prostaglandin F-2 alpha (PGF(2 alpha)) 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 PGE(2), but not that by PGF(2 alpha). PGE(2)-induced allodynia was not observed in N-methyl-D-aspartate (NMDA) receptor epsilon 1 subunit knockout mice and was sensitive to morphine. In contrast, PGF(1 alpha)-induced allodynia was not observed in NMDA epsilon 4 subunit knockout mice and was insensitive to morphine, Furthermore, while PGF(2 alpha) showed a capsaicin-insensitive feeble facilitatory action on evoked excitatory postsynaptic currents in dorsal horn neurons, PGE(2) 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 PGE(2)-induced allodynia.