Subcutaneous formalin and intraplantar carrageenan increase nitric oxide release as measured by in vivo voltammetry in the spinal cord

Abstract

The paper describes in vivo voltammetric detection of nitric oxide with carbon fibre microelectrodes at the lumbar spinal dorsal horn level of decerebrated–spinalized rats during peripheral noxious inflammatory processes. At the lumbar (L3–L4) dorsal horn level, a nitric oxide dependent peak of oxidation current (650mV), remaining stable for up to 4h ((92±5)% of control) could be detected indicating that significant amounts of nitric oxide are produced continuously. Following subcutaneous injection in the hindpaw of 50μl of 0.5% formalin the oxidation current rapidly increased ((115±5)% of control at 25min) and reached (120±6)% of control 1h later. Subsequently the voltammograms stabilized for up to 90min and decreased ((107±4)% at 124min). After an injection in the hindpaw of 150μl of 4% carrageenan, the voltammograms remained at control level for 1h and then the oxidation current increased continuously for up to 4h ((145±16)% of control at 240min); such an increase was reversed by ketamine. In these two models of inflammation, the delay in onset and the duration of the increases in NO release within the dorsal horn relate, to some extent, to the time course of the peripheral inflammatory processes, since they are shorter after formalin than after carrageenan. The results provide a direct in vivo demonstration that the intercellular messenger nitric oxide participates in the transmission of noxious afferent messages within the dorsal horn of the spinal cord following peripheral inflammation.