| Summary: | <p>Abstract</p> <p>Inflammation, trauma or nerve injury trigger low-level activity in C-fibres and may cause long-lasting hyperalgesia. Long-term potentiation (LTP) at synapses of primary afferent C-fibres is considered to underlie some forms of hyperalgesia. In previous studies, high- but not low-frequency conditioning stimulation of C-fibres has, however, been used to induce LTP in pain pathways. Recently we could show that also conditioning low-frequency stimulation (LFS) at C-fibre intensity induces LTP <it>in vitro </it>as well as in the intact animal, i.e. with tonic descending inhibition fully active. In the slice preparation, this form of LTP requires a rise in postsynaptic Ca<sup>2+</sup>-concentration and activation of Ca<sup>2+</sup>-dependent signalling pathways. Here, we investigated the signalling mechanisms underlying this novel form of LTP <it>in vivo</it>. We found that the signal transduction pathways causing LFS-induced LTP <it>in vivo </it>include activation of neurokinin 1 and N-methyl-D-aspartate receptors, rise of [Ca<sup>2+</sup>]<sub>i </sub>from intracellular stores and via T-type voltage-dependent Ca<sup>2+ </sup>channels, activation of phospholipase C, protein kinase C and Ca<sup>2+</sup>-calmodulin dependent kinase II. These pathways match those leading to hyperalgesia in behaving animals and humans. We thus propose that LTP induced by low-level activity in C-fibres may underlie some forms of hyperalgesia.</p>
|
|---|