Intracellular messengers involved in nociceptive behaviours induced by intrathecal (R,S)-3,5-dihydroxyphenylglycine

We investigated the role of two intracellular second messengers, extracellular signal-regulated protein kinase (ERK), and protein kinase C (PKC) in a model of persistent pain, using intrathecal (i.t) (R,S )-DHPG to induce spontaneous nociceptive behaviours (SNBs). SNBs were measured in animals that were treated with an ERK inhibitor (PD 98059), and a PKC inhibitor (GF 109203X) compared with controls. Mechanical allodynia, was measured using paw withdrawal thresholds in the von Frey test, and thermal hyperalgesia was measured using response latencies in the plantar test. In study 1, it was shown that spinal administration of PD 98059, dose-dependently decreased SNBs, and reduced mechanical allodynia and thermal hyperalgesia. In study 2, it was shown that i.t. pretreatment with the GF 109203X, reduced SNBs and thermal hyperalgesia, but not mechanical allodynia. These results suggest that both ERK and PKC are involved in SNBs and the concomitant and thermal hyperalgesia and possibly mechanical allodynia