Peripheral inflammation increases phosphoinositide activity in the rat dorsal horn

Abstract

Persistent pain leads to changes in the spinal cord that contribute to hyperalgesia and allodynia. The effort to characterize these changes has focused on neurotransmitters and receptors, while relatively little is known about pain-associated modulation of second-messenger responses. Nearly all neurotransmitters can activate the phosphoinositide (PI) second-messenger system which has been investigated using a method that localizes membrane-bound [ 3H]CDP–diacylglycerol (DAG) produced from the precursor [ 3H]cytidine [Science 249 (1990) 802]. The present study applied this method in spinal cord slices from rats injected with complete Freund's adjuvant in one hindpaw and from uninflamed control rats. Two days after the injection, slices were removed and maintained in vitro for pharmacological testing. Some slices were exposed to the acetylcholine agonist carbachol which is antinociceptive in the spinal cord. Inflammation resulted in increased baseline, unstimulated [ 3H]CDP–DAG accumulation, especially in superficial dorsal horn layers, as well as enhanced carbachol-stimulated labeling. These results suggest that persistent pain leads to neurochemical changes within the spinal cord that could potentially enhance responses to a spectrum of pain-modulating transmitters.