Peripheral inflammations are known to be able to cause hyperalgesia ascribed to peripheral and central mechanisms. Cellular mechanisms of the central component are not completely understood yet.
Intradermal or subcutaneous injections of formalin or capsaicin are frequently used models for peripheral inflammation in behavioral studies in humans and animals.
In the present study we could show that peripheral inflammation caused by intraplantar injection of formalin 5 % (n=6) or capsaicin 1 % (n=5) induces long-term potentiation (LTP) of synaptic transmission in spinal dorsal horn of anaesthesized adult rats, while injections of only the solvents of the noxious agents did not alter the synaptic plasticity (each with n=3). C-fiber-evoked field potentials were potentiated after application of the noxious agents to 172±2 % of control in formalin experiments and to 173±9 % of control in capsaicin experiments and for the whole experimental duration. This is a new aspect of the cellular mechanisms of central sensitization due to peripheral inflammation. As peripheral inflammation leads to low-frequency firing of primary afferents we applied an electrical low-frequency stimulus (LFS; 2 Hz for 2 min) to the sciatic nerve to have the conditioning stimulation under better control concerning duration and intensity compared to injecting the noxious agents. In all experiments LTP was induced with a mean area of C-fiber-evoked field potential of 330±42 % of control (n=14).
Recording of the signals lasted for up to 17 h. To verify if this LTP induced by a electrical LFS was indeed a good model for LTP induced by peripheral inflammation we applied the same agents as used in the behavioral studies of peripheral inflammation to diminish or abolish the animals nociceptive behavior. The NMDA-receptor-antagonist MK-801 and the NO-synthase-inhibitor L-NMMA were able to block LTP and the NK1-receptor-antagonist RP67580 diminished LTP compared to control (each with n=5), suggesting the NMDA-receptor and as well NO-synthases to be essential for induction of LTP by LFS, and showing the partial role of the NK1-receptor that it is playing in induction of LTP by LFS. These findings are in accordance to behavioral studies of peripheral inflammation. Long-term potentiation of C-fiber evoked field potentials could also be induced by LFS or a high-frequency stimulation (HFS) in young animals (postnatal day 25-28). Mean area of C-fiber-evoked field potentials increased to 294 ± 25% (mean ± SEM) of control one hour after LFS (n=4) respectively to 336 ± 59% of control after HFS (n=3). The NO-synthase inhibitor L-NMMA was not able to block LTP but significantly diminished LTP induced by LFS (n=6) and did not affect the LTP induced by HFS in 4 out of 5 experiments.
Taken together we suggest this model as a good basis for further experiments regarding hyperalgesia by natural noxious stimuli and in particular peripheral inflammation.