Potentiation of nociceptive activity in the neo-natal rat spinal cord by peripheral prostaglandins

EFFECTS OF BBADYHININ ON THE MEMBRANE OF SENSORY NEURCNES FROM ADULT RATS. H P Rang and R M Lindzayt, Sandoz Institute for Medical Research, 5 Cower Place, London WClE 6BN, England. Aim of Investigation: Bradykinin exerts a powerful excitatory effect on the nerve terminals of nociceptive zenzory neuronez, but little iz known of the mechanism by which it, or any other pain-producing substance, brings about this excitation. The aim, of this study waz to determine the nature of the conductance change that bradykinin produces on the somatic membrane of izolated zenzory neuronez. Methods: Dorsal root ganglion cells from adult rate were ieolated by trypzin/collzgertaw treatment, atid deposited on polyornithine/laminin coated cover zlipz, to which they adhered in 2-3 hours. Membrane current8 were studied by the whole-cell patch-clamp technique, and BK (l-10&4) was applied for 1-10s by prezeure injection cloze to the membrane. Rezultz: About 70% of the neuronez responded to BK, the proportion being similar in freshly izolated cell bodies and in culture6 up to 9 daye old, in which the neumnez had extensive neuritea. Three typez of response were obzerved: a) a brief outward current, recorded at depolarized membrane potentiale, aezociatdd with increazed K-conductance, b) a longer-lasting (1-lmin) inward current in about 10% of cells; associated with increased conductance, in about 30% of cells; c) an inward current at depolarized membrane potentiala, associated with inhibition of in about 70% of cells. Rezponsee b) or c) voltage sensitive K-currents, were zometiidez preceded by a). Conclusions Excitation of zenzory neuronez by bradykinin may result from an opening of (? cgtion) channels or from closure of K channels. The and the type of receptor-channel cellular specificity of these responses. linkage, are being jnveztigated. POTENTIATION OF NOCICEPJ'IVE ACTIVITYIN THE NEO-NATAL RAT SPINAL CORD BY PERIPHERAL PROSTAGLANDINS. M.N.Perkins*, J.A.Bettaney* and A.Dray. Sandoz Institute for Medical Research, 5 Gower Place, London WClE 6BN, United Kingdom. The neo-natal rat spinal cord-tail preparation -in vitro was used to investigate prostaglandin involvement in nociception. The spinal cord with tail attached was isolated from 1-2 day old rat PUPS* and the surface of the skin removed from the tail. The preparation was maintained at ZO-22'C with the cord and tail perfused separately with oxygenated artificial CSF. Extracellular recordings were made from one of the lumbar ventral roots (L3-L5). Chemical (capsaicin, caps 0.5-1nM; bradykinin, BK 0.5-lnM, for 10-12s) and thermal (hot CSF >45'C) noxious stimuli applied to the tail gave a depolarisation at the ventral root. PGE2 and PGF2c<(0.6nM) pretreatment of the tail enhanced the responses in the spinal cord to noxious stimuli as well as producing a ventral root depolarisationby themselves. Arachidonic acid (0.7-1.4nM), indomethacin (lOOpI+),nifedipine (20nM), BayK8644 (1nM) and CoC12 (l-2mM) applied to the tail had no effect on the responses to BK, caps or noxious heat. Perfusion of the tail with Ca2+ free CSF plus 100nM EGTA enhanced responses to BK and caps. CoC12 prevented the prostaglandin-inducedenhancement of the noxious stimuli. These results show that prostaglanding can directly stimulate peripheral nerve terminals and enhance peripheral nociceptive activity. This enhancement may involve calcium in its mechanism of action.