The contribution of GABAB receptor-mediated events to inflammatory pain processing: carrageenan oedema and associated spinal c-Fos expression in the rat.

Abstract

In this pharmacological study we have assessed the effect of baclofen, a selective GABAB receptor agonist, on spinal expression of the immediate early gene c-Fos and the peripheral oedema evoked by a prolonged peripheral inflammation due to intraplantar carrageenan. Baclofen was administered intravenously 30 min before intraplantar injection of carrageenan in freely moving rats. Three hours after carrageenan the number of spinal c-Fos protein-like immunoreactive neurons and peripheral (ankle and paw) oedema were assessed. For the two series of experiments the total number of control carrageenan-evoked c-Fos protein-like immunoreactive neurons in segments L4-L5 of the spinal cord was 176 +/- 6 and 177 +/- 9 c-Fos protein-like immunoreactive neurons per section, for carrageenan control with intravenous and intraplantar saline, respectively. c-Fos protein-like immunoreactive neurons were predominantly located in laminae I-II and V-VI of the dorsal horn of the spinal cord in carrageenan controls receiving intravenous (68 +/- 3 and 69 +/- 2 c-Fos protein-like immunoreactive neurons, respectively) and intraplantar (62 +/- 4 and 71 +/- 5 c-Fos protein-like immunoreactive neurons, respectively) saline. Pre-administered systemic baclofen (0.05, 1.5 and 3 mg/kg i.v.) dose dependently reduced the total number of c-Fos protein-like immunoreactive neurons (81 +/- 3, 66 +/- 4 and 49 +/- 4% of control total number of c-Fos protein-like immunoreactive neurons, respectively), with strongest effects on the number of deep (74 +/- 3, 60 +/- 3 and 43 +/- 4% of control, respectively) as compared with superficial (90 +/- 4, 77 +/- 5 and 59 +/- 5% of control, respectively) c-Fos protein-like immunoreactive neurons. The effects of systemic baclofen on the carrageenan-induced spinal c-Fos expression and both the paw and ankle oedema were positively correlated (r = 0.479, P < 0.05 and r = 0.733, P < 0.001, respectively). Intraplantar baclofen (50 and 100 micrograms in 50 microliters of saline), simultaneously injected with intraplantar carrageenan, did not significantly influence carrageenan-evoked spinal c-Fos expression or ankle oedema. Despite the fact that the highest dose of intraplantar baclofen significantly reduced paw oedema (23 +/- 3% reduction of control paw oedema), our results are clearly in favour of a spinal site of action of systemic baclofen.