SPINAL-CORD SP RELEASE AND HYPERALGESIA IN MONOARTHRITIC RATS - INVOLVEMENT OF THE GABA(B) RECEPTOR SYSTEM

1 Monoarthritis was induced in Lewis rats by interdermal injection in the left hind paw of a suspension of Mycobacterium tuberculosis in min eral oil (500 mu g 100 mu l(-1)). Controls were injected with 100 mu l mineral oil. 2 Withdrawal latencies to thermal stimuli of the inflame d paw, the contralateral and both paws of control rats were measured a t daily intervals after injection by the plantar test. 3 After detecti on of the pain threshold, rat spinal cords were removed and horizontal dorsal slices were mounted in a 3-compartment bath to measure electri cally-evoked release of substance P-like immunoreactivity (SP-LI). 4 T he inflamed paw of monoarthritic rats exhibited a lower pain threshold to thermal stimuli than the contralateral paw of the same animals and both paws of control rats. Inflamed paw hyperalgesia was maximal two days after injection, and declined gradually between 7 to 21 days with no evidence of excitability of withdrawal reflexes after 28 days. 5 D uring the 28 days study, monoarthritic rats gained less weight than co ntrol rats. 6 Electrical stimulation of the dorsal roots attached to r at isolated spinal cord slices induced a significant increase (174 +/- 18% of basal outflow which was 30.3 fmol 8 ml(-1), n = 5) in SP-LI re lease. 7 One-week after induction of inflammation no differences in th e amount of SP-LI released from the spinal cord of incomplete Freund's adjuvant-treated rats (IFA) and Freund's adjuvant-treated rats (CFA) were detected. Two weeks after, CFA spinal cord tended to release more SP-LI than IFA cords and, 21 days after injection, the spinal cord of CFA rats released significantly more peptide than IFA rats (17.8 +/- 2.8 fmol ml(-1), n = 12 and 6.9 +/- 3.2 fmol ml(-1), n = 9, respective ly). 8 Twenty-one days after treatment, the evoked release from monoar thritic rat spinal cords was increased by 263 +/- 42% (n = 3) in the p resence of the GABA(B) receptor antagonist, CGP 36742 (100 mu M) which also significantly potentiated monoarthritis-induced hyperalgesia up to 45 min after injection (100 mg kg(-1), i.p.). 9 These findings may provide a basis for a novel approach to chronic pain therapy but also an explanation for the lack of analgesia produced by the GABA(B) agoni st, baclofen, in chronic as compared to acute pain.