title: Molecular plasticity of primary nociceptive neurons: relations of the NGF-c-jun system to neurotomy and chronic pain.
abstract: Neurotomy is widely used as a model of chronic, intractable pain, the proverbial "crux medicorum". Immunohistochemical aspects of this chronic pain model are discussed in this paper, with the aim of shedding new light on the pathomechanism and possible therapeutical consequences. Central terminals of nociceptive neurons contain substance P, somatostatin and calcitonin generelated peptide or exhibit fluoride resistant acid phosphatase and thiamine monophosphatase enzyme reaction in the superficial dorsal horn of the spinal cord and in analogous structures of the brain stem. These neuropeptides and neuroproteins are expressed by the related dorsal root ganglion cells and transported via orthograde axoplasmic transport via dorsal roots to the central nervous system. Transection of the ipsilateral, segmentally related peripheral sensory nerve results in transganglionic degenerative atrophy of central terminals of primary nociceptive neurons. Transganglionic degenerative atrophy is characterized by marked ultrastructural alterations superficially similar to, but essentially differing from the signs of Wallerian degeneration which ensue after dorsal rhizotomy. Transganglionic degenerative atrophy is accompanied by depletion of marker neuropeptides and enzymes, and later by the expression of vicarious neuropeptides such as vasoactive intestinal polypeptide, neuropeptide Y and galanin and of the enzyme choline acetyl transferase. Consequences of blockade of retrograde axoplasmic transport of the nerve growth factor elicited either by perineural application of microtubule inhibitors or by perineural administration of anti-nerve growth factor are similar to peripheral neurotomy. According to recent studies described in this paper, the blockade of nerve growth factor supply to primary nociceptive neurons induces activation of c-jun in nuclei of primary nociceptive neurons probably responsible for the plasticity of the neuropeptide and neuroprotein synthesizing machinery. In contrast, invasion of and formation of pericellular baskets by noradrenergic axons can be elicited only by axotomy and not by blockade of retrograde axoplasmic transport. Involvement of nerve growth factor and the nerve growth factor-dependent immediate early genes in neuroplasticity of neuropeptidergic primary sensory neurons raise the possibility of a gene therapy of chronic intractable pain.
authors.affiliation: Department of Anatomy, Albert Szent-Györgyi Medical and Pharmaceutical Center, University of Szeged, Hungary. csillik@anat-fm.szote.u-szeged.hu
authors.forename: Bertalan
authors.initials: B
authors.lastname: Csillik
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Janka
authors.forename: István
authors.initials: I
authors.lastname: Boncz
authors.forename: János
authors.initials: J
authors.lastname: Kálmán
authors.forename: András
authors.initials: A
authors.lastname: Mihály
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Knyihár
mesh_terms: D000818:Animals; D001284:Atrophy; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008959:Models, Neurological; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D009619:Nociceptors / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D010146:Pain / Q000473:pathology / Q000503:physiopathology*; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D051381:Rats; D013373:Substance P / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D013373:Substance P; D014750:Vincristine; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide