THE CONTRIBUTION OF GABA(B) RECEPTOR-MEDIATED EVENTS TO INFLAMMATORY PAIN PROCESSING - CARRAGEENAN EDEMA AND ASSOCIATED SPINAL C-FOS EXPRESSION IN THE RAT

In this pharmacological study we have assessed the effect of baclofen, a selective GABA(B) receptor agonist, on spinal expression of the imm ediate early gene c-Fos and the peripheral oedema evoked by a prolonge d peripheral inflammation due to intraplantar carrageenan. Baclofen wa s administered intravenously 30 min before intraplantar injection of c arrageenan in freely moving rats. Three hours after carrageenan the nu mber of spinal c-Fos protein-like immunoreactive neurons and periphera l (ankle and paw) oedema were assessed. For the two series of experime nts 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 sectio n, for carrageenan control with intravenous and intraplantar saline, r espectively. c-Fos protein-like immunoreactive neurons were predominan tly 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 intra plantar (62 +/- 4 and 71 +/- 5 c-Fos protein-like immunoreactive neuro ns, respectively) saline. Pre-administered systemic baclofen (0.05, 1. 5 and 3 mg/kg i.v.) hose 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 su perficial (90 +/- 4, 77 +/- 5 and 59 +/- 5% of control, respectively) c-Fos protein like immunoreactive neurons: The effects of systemic bac lofen on the carrageenan-induced spinal c-Fos expression and both the paw and ankle oedema were positively correlated (r = 0.479, P < 0.05 a nd r = 0.733, P < 0.001, respectively). Intraplantar baclofen (50 and 100 mu g in 50 mu l of saline), simultaneously injected with intraplan tar carrageenan, did not significantly influence carrageenan-evoked sp inal c-Fos expression or ankle oedema. Despite the fact that the highe st dose of intraplantar baclofen significantly reduced paw oedema (23 +/- 3% reduction of control paw oedema), our results are clearly in fa vour of a spinal site of action of systemic baclofen. Copyright (C) 19 96 IBRO.