Plasticity in mice nociceptive spinal circuits -role of cell adhesion molecules.

Research output: ThesisDoctoral Thesis (compilation)

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Abstract

Introduction: To understand the function of the genes and their products in the pain system, studies will have to deal with complex issues related to intercellular communication, e.g. plasticity in neuronal networks. To provide a basis for such studies, the present thesis compares basic features of the nociceptive spinal systems including the organization of nociceptive withdrawal reflexes (NWR), laminar organization of the nociceptive C-fibre input to the spinal cord and plastic mechanisms in the mouse and rat. On this basis, the role of adhesion molecules, in particular L1 adhesion molecules, in the nociceptive system is analyzed for the first time by using mutated mice.

Results: It is confirmed that sensorimotor transformations performed by the NWR circuits abide the same principles as in the rat, at least for two of the wild-type mouse strains tested. This finding indicates that mice NWR has a modular organization as previously demonstrated in the rat. Interestingly, mouse strains with a deficit in LTP mechanisms also exhibit a deficient sensorimotor transformation, suggesting that LTP mechanisms are involved in the developmental mechanisms that fine-tune the NWR. Furthermore, basic features such as nociceptive C-fibre evoked field potentials and response characteristics like short term potentiation in deep dorsal horn neurones appear to be very similar in mouse and rat. By contrast, marked differences were found in the properties of nociceptive transmission in the superficial laminae. In particular, apparently normal wild type mice seem to lack both short and long term potentiation in the first order synapses, mechanisms that are powerful in the rat. These findings suggest that the current view on the locus of the central sensitization mechanisms needs to be reconsidered.

In the second part of the thesis, the role of the cell adhesion molecule L1 in the pain system was studied in mutated mice. Interestingly, these animals were found to be almost analgesic. This hypoalgesia is not due to a general lack of nociceptive input to the spinal cord as evidenced by a normal termination pattern of C fibres and C fibre evoked potentials in the superficial laminae in L1 deficient mice. Instead, a selective defect in the nociceptive transmission to the deeper laminae of the dorsal horn and a markedly reduced wind-up in the WDR neurones were found.

Conclusions: The present thesis demonstrates that there are important differences in plastic mechanisms in the spinal nociceptive pathways in the mouse and rat. In addition, it points to a key role of adhesion molecules in pain transmission.

This work was supported by grants from the Swedish Research Council (M) (Proj no 1013), Kocks Foundation, Medical Faculty of Lund.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Department of Experimental Medical Science
Supervisors/Advisors
  • Schouenborg, Jens, Supervisor
Award date2005 Nov 4
Publisher
Print ISBNs91-85439-95-9
Publication statusPublished - 2005

Bibliographical note

Defence details

Date: 2005-11-04
Time: 09:00
Place: Segerfalks lecture hall Wallenberg Neurocentrum Sölvegatan 17 Lund

External reviewer(s)

Name: Laird, Jennifer
Title: Adjunct Professor
Affiliation: Dept of Pharmacology and Experimental Therapeutics, Faculty of Medicine, McGill University, (Montrea

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<div class="article_info">Jonas Thelin and Jens Schouenborg. <span class="article_issue_date">2005</span>. <span class="article_title">Disturbed nociceptive processing in mice with deficient hippocampal LTP</span> (submitted)</div>
<div class="article_info">Jonas Thelin, Alexandra Waldenström, Udo Bartsch, Melitta Schachner and Jens Schouenborg. <span class="article_issue_date">2003</span>. <span class="article_title">H eat nociception is severely reduced in a mutant mouse deficient for the L1 adhesion molecule</span> <span class="journal_series_title">Brain Research</span>, <span class="journal_volume">vol 965</span> <span class="journal_pages">pp 75-82</span>.</div>
<div class="article_info">Jonas Thelin, Melitta Schachner and Jens Schouenborg. <span class="article_issue_date"></span>. <span class="article_title">Intrasegmental transmission of nociceptive input in normal and L1 deficient mice</span> (manuscript)</div>

Subject classification (UKÄ)

  • Basic Medicine

Keywords

  • Long term-potentiation
  • Cell adhesion molecule
  • Pain
  • Somatosensory imprinting
  • Medicin (människa och djur)
  • Medicine (human and vertebrates)
  • Nociceptive withdrawal reflex
  • Species differences
  • Central sensitisation
  • Mouse strains
  • Spinal cord

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