EFFECT OF PERIPHERAL AXOTOMY ON DORSAL-ROOT GANGLION NEURON PHENOTYPEAND AUTOTOMY BEHAVIOR IN NEUROPEPTIDE Y-DEFICIENT MICE

The lumbar 5 (L5) dorsal root ganglia (DRGs) were studied in neuropept ide tyrosine (NPY)-deficient (-/-) and wild type (+/+) mice after unil ateral sciatic nerve transection using in situ hybridization and immun ohistochemistry. NPY, galanin and two NPY receptors (Y-Rs) were analyz ed as well as self-mutilation behaviour (autotomy) and nociceptive thr esholds. No difference between wild type and NPY-deficient mice was se en in the tail-flick or hot plate test. However, -/- mice showed a muc h stronger autotomy behaviour than wild type mice. NPY was not found i n L5 DRGs in -/- mice, not even after axotomy. Galanin was upregulated to the same extent after axotomy in NPY-deficient and wild type mice. Y1- and Y2-R mRNAs were found mainly in small DRG neuron profiles. Bo th receptor mRNAs were downregulated after axotomy, to about the same extent in NPY-deficient as in wild type mice. In control and contralat eral ganglia the mRNA levels of both receptors were lower in NPY-defic ient mice than in wild type mice. The contralateral Y2-R mRNA levels d id not reach control values in the NPY-deficient mice, as they did in the wild type mice. In both strains the YI-R protein was decorating th e somatic plasmalemma. The present results suggest that lack of NPY ma y cause exaggerated autotomy, a self-mutilation behaviour possibly rel ated to pain sensation, in agreement with the described analgesic effe ct of NPY. Although significant differences in levels of Y1- and espec ially Y2-R mRNAs were observed between wild type and NPY-deficient mic e, they were only moderate. These findings suggest that expression, re gulation, localization and possible function of Y1- and Y2-Rs are not dependent on presence of the endogenous ligand. Also, deletion of NPY does not seem to influence the expression of the partly coexisting pep tide galanin. (C) 1998 Elsevier Science BN. All rights reserved.