MARKED INCREASE IN CHOLECYSTOKININ-B RECEPTOR MESSENGER-RNA LEVELS IN RAT DORSAL-ROOT GANGLIA AFTER PERIPHERAL AXOTOMY

It is now well established that the expression of peptides in rat primary sensory neurons is dramatically changed in response to peripheral nerve injury. Thus, as first shown by Jessell et al.15 peripheral axotomy causes a decrease in substance P levels in the dorsal horn of the corresponding spinal cord segments, and this is due to down-regulation of peptide synthesis in dorsal root ganglion neurons.22 In contrast, other peptides such as vasoactive intestinal polypeptide and peptide histidine isoleucine,27 galanin12 and neuropeptide Y32 are all markedly upregulated in the rat L4 and L5 dorsal root ganglia after sciatic nerve sectioning. The levels of another peptide, cholecystokinin and its messenger RNA are normally very low or undectable in rat primary sensory neurons,5,20,24,25,26 but after peripheral axotomy approximately 30% of the ganglion neurons express cholecystokinin messenger RNA.30 During the last few years a number of peptide receptors have been cloned, and they all belong to the family of G-protein coupled receptors with seven membrane spanning segments,21 among them the two cholecystokinin receptors cholecystokinin(A) and cholecystokinin(B).17,23,34 Ghilardi et al.11 have recently described presence of cholecystokinin(B) binding sites in rat dorsal root ganglia neurons. In the present study we report that the messenger RNA for the cholecystokinin(B) receptor is present at very low levels in normal dorsal root ganglia of the rat, but axotomy causes a very marked increase in the number of sensory neurons of all sizes expressing cholecystokinin(B) receptor messenger RNA, suggesting an increased sensitivity to cholecystokinin for many primary sensory neurons of different modalities after lesion.