Central neuropathic pain (CNP) is an important problem following spinal cord injury (SCI), because it severely affects the quality of life of SCI patients. As in the patient population, the majority of rats develop significant allodynia (CNP rats) after moderate SCI. However, about 10% of SCI rats do not develop allodynia, or develop significantly less allodynia than CNP rats (non-CNP rats). To identify transcriptional changes underlying CNP development after SCI, we used Affymetrix DNA microarrays and RNAs extracted from the spinal cords of CNP and non-CNP rats. DNA microarry analysis showed significantly increased expression of a number of genes associated with inflammation and astrocytic activation in the spinal cords of rats that developed CNP. For example, mRNA levels of glial fibrilary acidic protein (GFAP) and Aquaporin 4 (AQP4) significantly increased in CNP rats. We also found that GFAP, S100b and AQP4 protein elevation persisted for at least 9 months throughout contused spinal cords, consistent with the chronic nature of CNP. Thus, we hypothesize that CNP development results, in part, from dysfunctional, chronically ''over-activated'' astrocytes. Although, it has been shown that activated astrocytes are associated with peripheral neuropathic pain, this has not previously been demonstrated in CNP after SCI.
I. BACKGROUNDThe concept that some decompositions of ions in the gas phase take place through ion-neutral complexes has advanced sufficiently since Morton's classic review (1) to make timely a fresh survey of the subject. The reader is referred to Morton's article for discussion of relationships between complex-mediated reactions of ions in the gas phase, solvolysis reactions, unimolecular eliminations from neutrals, and conventional unimolecular reactions of ions. This review primarily addresses the role of ion-neutral complexes in unimolecular decompositions. The binding forces that maintain ion-neutral complexes and the transition states for their formation and reaction will be described first. This description is extended by discussing studies of ion-molecule reactions,'molecular orbital calculations, and decompositions of ionized steroids that illuminate the nature of ion-neutral complexes. Proposed criteria for distinguishing complex-mediated reactions from "conventional" reactions are then listed. Finally, ion-neutral eomplex-mediated reactions are surveyed. Although to keep the review to readable length the survey is not exhaustive, representative examples of complex-mediated reactions are presented. The term ion-neutral complex is applied to a species in which an ion and a neutral are held in association chiefly by electrostatic attractions. Species such as 'CH20H2 + , which have been referred to as ion-neutral complexes (2), but in which the partners are joined by a covalent bond (3), will not be considered.The suggestion of Rylander and Meyerson (4) that ionized alkyl benzenes decompose through cationated cyclopropanes was perhaps the first proposed ion-neutral complex-mediated dissociation of an ion. Although loss of water through [RCH==CHCH=N+=N-OH-] formed from an adduct of an ionmolecule reaction was proposed in 1977 (5), current investigations of ion-neutral complexes as intermediates in unimolecular dissociations were sparked by the
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