Peripheral inflammation increases phosphoinositide activity in the rat dorsal horn.

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 [(3)H]CDP-diacylglycerol (DAG) produced from the precursor [(3)H]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 [(3)H]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.

Neuronal primary cilia: a review.

Primary cilia in neurons have often been regarded as rare, vestigial curiosities. However, neuronal cilia are now gaining recognition as ubiquitous organelles in the mammalian brain, raising speculation about what their functions may be. They might have some features tailored for the nervous system and others that serve needs shared by a spectrum of other cell types. Here we review clues from the literature and present new data supporting several possibilities for the significance of neuronal cilia. Our immunocytochemical results show regional heterogeneity in neuronal cilia. Brain regions nearer to the cerebral ventricles had longer cilia, suggesting that they might sense chemicals such as peptides, originating from cerebrospinal fluid. In mutant Tg737(orpk)mice, most brain regions appeared to be missing cilia. The importance of intraflagellar transport proteins establishes a functional link between neuronal cilia and other primary cilia.