Acute and persistent nociceptive paw sensitisation in mice: the involvement of distinct signalling pathways

Abstract

Aims Many fundamental pharmacological studies in pain and inflammation have been performed on rats. However, the pharmacological findings were generally not extended to other species in order to increase their predictive therapeutic value. We studied acute and chronic inflammatory nociceptive sensitisation of mouse hind paws by prostaglandin E2 (PGE2) or dopamine (DA), as previously described in rats. We also investigated the participation of the signalling pathways in acute and persistent sensitisation. Main methods Mechanical sensitisation (hypernociception) induced by intraplantar administrations of PGE2 or DA was evaluated with an electronic pressure meter. The signalling pathways were pharmacologically investigated with the pre-administration of adenylyl cyclase (AC), cAMP-dependent protein kinase (PKA), protein kinase Cε (PKCε), and the extracellular signal-related kinase (ERK) inhibitors. Key findings Single or 14 days of successive intraplantar injections of PGE2 or DA-induced acute and persistent hypernociception (lasting for more than 30 days), respectively. The involvement of AC, PKA or PKCε was observed in the acute hypernociception induced by PGE2, while PKA or PKCε were continuously activated during the period of persistent hypernociception. The acute hypernociception induced by DA involves activation of ERK, PKCε, AC or PKA, while persistent hypernociception implicated ERK activation, but not PKA, PKCε or AC. Significance In mice, acute and persistent paw sensitisation involves the different activation of kinases, as previously described for rats. This study opens the possibility of comparing pharmacological approaches in both species to further understand acute and chronic inflammatory sensitisation, and possibly associated genetic manipulations.