The Effect of Amitriptyline on Ectopic Discharge of Primary Afferent Fibers in the L5 Dorsal Root in a Rat Model of Neuropathic Pain

2009 ◽  
Vol 108 (5) ◽  
pp. 1671-1679 ◽  
Author(s):  
Xin Su ◽  
Annie H. Liang ◽  
Mark O. Urban
2003 ◽  
Vol 81 (7) ◽  
pp. 663-682 ◽  
Author(s):  
Fuad A Abdulla ◽  
Timothy D Moran ◽  
Sridhar Balasubramanyan ◽  
Peter A Smith

Nociceptive pain alerts the body to potential or actual tissue damage. By contrast, neuropathic or "noninflammatory" pain, which results from injury to the nervous system, serves no useful purpose. It typically continues for years after the original injury has healed. Sciatic nerve lesions can invoke chronic neuropathic pain that is accompanied by persistent, spontaneous activity in primary afferent fibers. This activity, which reflects changes in the properties and functional expression of Na+, K+, and Ca2+ channels, initiates a further increase in the excitability of second-order sensory neurons in the dorsal horn. This change persists for many weeks. The source of origin of the pain thus moves from the peripheral to the central nervous system. We hypothesize that this centralization of pain involves the inappropriate release of peptidergic neuromodulators from primary afferent fibers. Peptides such as substance P, neuropeptide Y (NPY), calcitonin-gene-related peptide (CGRP), and brain-derived neurotrophic factor (BDNF) may promote enduring changes in excitability as a consequence of neurotrophic actions on ion channel expression in the dorsal horn. Findings that form the basis of this hypothesis are reviewed. Study of the neurotrophic control of ion channel expression by spinal peptides may thus provide new insights into the etiology of neuropathic pain.Key words: neuropathic pain, spinal cord injury, allodynia, dorsal root ganglion, axotomy.


1949 ◽  
Vol 32 (4) ◽  
pp. 409-443 ◽  
Author(s):  
David P. C. Lloyd ◽  
A. K. McIntyre

The "dorsal root potential" consists of five successive deflections designated for convenience, D.R.I, II, III, IV, and V. Of these, D.R.V alone constitutes the dorsal root potential of prior description. A study has been made of the general properties of those deflections not previously described. Dorsal root potentials are electrotonic extensions into the extramedullary root segment, the result of electrical interactions within the cord comparable to those that have been studied in peripheral nerve. Although the anatomical and electrical conditions of interaction are infinitely more complex in the cord than in nerve, it is seen that the fact of parallel distribution of primary afferent fibers pertaining to neighboring dorsal roots provides a sufficient anatomical basis for qualitative analysis in the first approximation of dorsal root potentials. An extension of the theory of interaction between neighboring nerve fibers has been made to include an especial case of interaction between fibers orientated at right angles to one another. The predictions have been tested in a nerve model and found correct. Given this elaboration, and the stated anatomical propositions, existing knowledge of interaction provides an adequate theoretical basis for an elementary understanding of dorsal root potentials. The study of general properties and the analysis of dorsal root potentials have led to the formulation of certain conclusions that follow. D.R.I, II, and III record the electrotonic spread of polarization resulting from the external field of impulses conducted in the intramedullary segment and longitudinal trajects of primary afferent fibers. D.R.IV arises in part as the result of activity in primary afferent fibers, and in part as the result of activity in secondary neurons. In either case the mode of production is the same, and the responsible agent is residual negativity in the active collaterals, or, more precisely, the external field of current flow about the collaterals during the period of residual negativity. Current flow about active primary afferent collaterals during the period of residual negativity is the agent for residual facilitation of monosynaptic reflex pathways. Since the changes in reflex threshold follow the course of residual negativity there is no need to postulate especial properties for prolonging action at regions the threshold of which is measured by means of monosynaptic test reflexes. D.R.V results from polarization of primary afferent fibers by current flow about secondary neurons. There is indication that somata rather than axons of secondary neurons generate the polarizing currents. Similarity between D.R.V and the positive intermediary potential further indicates that soma gradients established during the recovery cycle are responsible for D.R.V. Little or no net polarization of primary afferent fibers results from activity confined to the contralateral gray substance, the dorsal root potentials in contralateral recording resulting from interaction in the dorsal column or in the ipsilateral gray substance following decussation of contralaterally evoked activity. During the course of asphyxia the initial defect in reflex pathways is the failure of secondary neurons to respond to primary impulses. Subsequently block is established at the branching zone of primary afferent fibers. A relation exists between the sequence of dorsal root potentials and the cord potential sequence, the major departure from exact correspondence occurring in the region of D.R.IV and the negative intermediary potential and being of a nature to suggest that different aspects of internuncial activity are emphasized by the two methods of leading.


2011 ◽  
Vol 4 (2) ◽  
pp. 343-365 ◽  
Author(s):  
Eiichi Kumamoto ◽  
Kotaro Mizuta ◽  
Tsugumi Fujita

2001 ◽  
Vol 21 (23) ◽  
pp. 9367-9376 ◽  
Author(s):  
David M. Cain ◽  
Paul W. Wacnik ◽  
Michelle Turner ◽  
Gwen Wendelschafer-Crabb ◽  
William R. Kennedy ◽  
...  

1999 ◽  
Vol 81 (4) ◽  
pp. 1636-1644 ◽  
Author(s):  
H. Richard Koerber ◽  
Karoly Mirnics ◽  
Anahid M. Kavookjian ◽  
Alan R. Light

Ultrastructural analysis of ectopic synaptic boutons arising from peripherally regenerated primary afferent fibers. The central axons of peripherally regenerated Aβ primary sensory neurons were impaled in the dorsal columns of α-chloralose-anesthetized cats 9–12 mo after axotomy. The adequate peripheral stimulus was determined, and the afferent fibers intracellularly stimulated while simultaneously recording the resulting cord dorsum potentials (CDPs). Fibers that successfully had reinnervated the skin responded to light tactile stimulation, and evoked CDPs that suggested dorsally located boutons were stained intracellularly with horseradish peroxidase (HRP). Two HRP-stained regenerated Aβ afferent fibers were recovered that supported large numbers of axon collaterals and swellings in laminae I, IIo, and IIi. Sections containing the ectopic collateral fibers and terminals in the superficial dorsal horn were embedded in plastic. Analyses of serial ultrathin sections revealed that ectopic projections from both regenerated fibers supported numerous synaptic boutons filled with clear round vesicles, a few large dense core vesicles (LDCVs) and several mitochondria (>3). All profiles examined in serial sections (19) formed one to three asymmetric axo-dendritic contacts. Unmyelinated portions of ectopic fibers giving rise to en passant and terminal boutons often contained numerous clear round vesicles. Several boutons (47%) received asymmetric contacts from axon terminals containing pleomorphic vesicles. These results strongly suggest that regenerated Aβ fibers activated by light tactile stimuli support functional connections in the superficial dorsal horn that have distinct ultrastructural features. In addition, the appearance of LDCVs suggests that primary sensory neurons are capable of changing their neurochemical phenotype.


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