NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia.

The transient receptor potential ion channel, TRPV1 plays an essential role in the development of inflammatory thermal hyperalgesia. We investigated the dependence of inflammatory TRPV1 induction on neurotrophic factor. Rat dorsal root ganglia (DRG) neurons were classified according to immunostaining for trk-A and IB4 and the effects of antibodies against NGF or GDNF on TRPV1 expression within the groups were then analysed by immunohistochemical means. The data were compared with the time course of trophic factor expression and the effects of their antibodies on thermal hyperalgesia against radiant heat after inflammation. Although the levels of both NGF and GDNF were increased by inflammation, NGF rapidly and transiently increased whereas GDNF increased gradually over a period of approximately one week. TRPV1 expression was increased within both trk-A positive and IB4 positive neurons after inflammation. Increased TRPV1 expression within trk-A positive neurons was prevented by anti-NGF but not by anti-GDNF, whereas TRPV1 induction within the IB4 positive group was blocked by anti-GDNF but not by anti-NGF. Both antibodies prevented the short latency of withdrawing an inflamed paw from radiant heat. These results suggest that inflammation differentially increases both NGF and GDNF, which facilitate TRPV1 expression within distinctive neurons to induce thermal hyperalgesia.