Skip to main content
Article thumbnail
Location of Repository

Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the spared nerve injury model of neuropathic pain

By Erika Polgar, D.I. Hughes, A.Z. Arham and A.J. Todd

Abstract

It has been proposed that death of inhibitory interneurons in the dorsal horn contributes to the neuropathic pain that follows partial nerve injury. In this study, we have used two approaches to test whether there is neuronal death in the dorsal horn in the spared nerve injury (SNI) model. We performed a stereological analysis of the packing density of neurons in laminas I-III 4 weeks after operation and found no reduction on the ipsilateral side compared with that seen on the contralateral side or in sham-operated or naive rats. In addition, we used two markers of apoptosis, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) staining and immunocytochemical detection of cleaved (activated) caspase-3. Neither of these methods demonstrated apoptotic neurons in the dorsal spinal cord 1 week after operation. Although TUNEL-positive cells were present throughout the gray and white matter at this stage, they were virtually all labeled with antibody against ionized calcium-binding adapter molecule 1, a marker for microglia. All animals that underwent SNI showed clear signs of tactile allodynia affecting the ipsilateral hindpaw. These results suggest that a significant loss of neurons from the dorsal horn is not necessary for the development of tactile allodynia in the SNI model

Year: 2005
OAI identifier: oai:eprints.gla.ac.uk:10700
Provided by: Enlighten

Suggested articles

Citations

  1. (1992). A consideration of neural counting methods. doi
  2. (1996). A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand proteinexpressedinamonocyticlineage.BiochemBiophysResCommun 224:855–862.
  3. (1988). A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. doi
  4. (1993). A quantitative analysis of microglial cell reaction in central primary sensory projection territories following peripheral nerve injury in the adult rat. Exp Brain Res 96:19–27. doi
  5. (1998). A quantitative study of neurons which express neurokinin 1 or somatostatin sst2a receptor in rat spinal dorsal horn. doi
  6. (2001). A-fibersensoryinput inducesneuronalcelldeathinthedorsalhornoftheadultratspinalcord.
  7. (2004). Activecaspase-3 expressionduringpostnataldevelopmentofratcerebellumisnotsystematically or consistently associated with apoptosis.
  8. (2002). Apoptotic gene expression in the lumbar dorsal horn in a model neuropathic pain in rat. doi
  9. (2003). Autonomicand motor neuron death is progressive and parallel in a lumbosacral ventral root avulsion model of cauda equina injury.
  10. (1989). Behavioral and anatomic correlates of the tactileevoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists. doi
  11. (2004). Blockade of glutamate mGlu5 receptors in a rat model of neuropathic pain prevents early overexpression of pro-apoptotic genes and morphological changes in dorsal horn lamina II. doi
  12. (2002). Caspases on the brain. doi
  13. (2001). Cell death in the superficial dorsal horn in a model of neuropathic pain. doi
  14. (1998). ChangesinGAD-andGABA-immunoreactivityinthespinaldorsalhorn afterperipheralnerveinjuryandpromotionofrecoverybylumbartransplants of immortalized serotoninergic precursors.
  15. (2002). Characterization of neuronal death induced by focally evoked limbic seizures in the C57BL/6 mouse. doi
  16. (1993). Coimbra A doi
  17. (2002). Comparison of calpain and caspase activities in the adult rat brain after transient forebrain ischemia. doi
  18. (1980). Efficientanalysisofexperimentalobservations.AnnuRev Pharmacol Toxicol 20:441–462.
  19. (1993). Estimateofthetotalnumberofneuronsand glial and endothelial cells in the rat spinal cord by means of the optical disector.
  20. (1999). GABAergic neurons that contain neuropeptide Y selectively target cells with the neurokinin 1 receptor in laminae III and IV of the rat spinal cord.
  21. (2002). Immunohistochemical and biochemical assessmentofcaspase-3activationandDNAfragmentationfollowingtransient focal ischemia in the rat. doi
  22. (2003). Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain. doi
  23. (2002). Injury-induced spinal motor neuron apoptosis is preceded by DNA single-strand breaks and is p53- and Bax-dependent. doi
  24. (1973). Investigation of glialcellsinsemithinsections.I.Identificationofglialcellsinthebrainof young rats.
  25. (2004). Lackofevidenceforsignificant neuronal loss in laminae I-III of the spinal dorsal horn of the rat in the chronic constriction injury model.
  26. (2004). Lidocaine attenuates apoptosis in the ischemic penumbra and reduces infarct size after transient focal cerebral ischemia in rats. doi
  27. (1997). Loss of GABAimmunoreactivity in the spinal dorsal horn of rats with peripheral nerve injury and promotion of recovery by adrenal medullary grafts. doi
  28. (1998). Microglia-specific localisation of a novel calcium binding protein, doi
  29. (1995). Microglial turnover in the injured CNS: activated microglia undergo delayed DNA fragmentation following peripheral nerve injury. doi
  30. (2001). Mild cerebral ischemia induces loss of cyclin-dependent kinase inhibitors and activation of cell cycle machinery before delayed neuronal cell death. doi
  31. (1997). Molecularsignalsresponsibleforthereorganizationofthe synaptic circuitry of the dorsal horn after peripheral nerve injury: the mechanismsoftactileallodynia.In:Molecularneurobiologyofpain(Borsook D, ed), pp 171–200.
  32. (1992). NeuN, a neuronal specific nuclear protein in vertebrates.
  33. (2003). Neurodegeneration in the dorsal horn of the spinal cord contributes to persistent pain after peripheral nerve injury. Soc Neurosci Abstr 29:696.3. SivilottiL,WoolfCJ
  34. (2002). Neuronal apoptosis associated with morphine tolerance: evidence for an opioid-induced neurotoxic mechanism.
  35. (1994). Nociceptor modulated centralsensitizationcausesmechanicalhyperalgesiainacutechemogenic and chronic neuropathic pain. doi
  36. (1995). Olfactoryexperiencemodulatesapoptosisinthe developing olfactory bulb.
  37. (2002). On counting and counting errors. doi
  38. (2002). Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord.
  39. (2001). Pathobiology of neuropathic pain. doi
  40. (1998). Peripheralnerve insultinducesNMDAreceptor-mediated,delayeddegenerationinspinal neurons.
  41. (1997). Prostaglandin E1 prevents apoptotic cell death in superficial dorsal horn of rat spinal cord. doi
  42. (1994). Quantitative assessment of tactile allodynia in the rat paw.
  43. (2003). Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain. doi
  44. (2000). Spared nerve injury: an animal model of persistent peripheral neuropathic pain. doi
  45. (2005). Spinal p38beta isoform mediates tissue injury-induced hyperalgesia and spinal sensitization. doi
  46. (1991). Spinalcordmicroglialcells and DRG satellite cells rapidly respond to transection of the rat sciatic nerve.
  47. (1999). Stereological methods for estimating the total number of neurons and synapses: issues of precision and bias. doi
  48. (1999). The apoptosis cascade–morphologicalandimmunohistochemicalmethodsforitsvisualization.Anat Embryol
  49. (1984). The cytoarchitectonic organization of the spinal cord in the rat. I. The lower thoracic and lumbosacral cord. doi
  50. (1984). The unbiased estimation of number and sizes of arbitrary particles using the disector. doi
  51. (1988). Three-dimensionalcounting:anaccurateand direct method to estimate numbers of cells in sectioned material.
  52. (1990). Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.