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Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model.

Leichsenring A, Bäcker I, Wendt W, Andriske M, Schmitz B, Stichel CC, Lübbert H - BMC Neurosci (2008)

Bottom Line: While for a long time, proteases were mainly considered as protein degrading enzymes, they are now receiving growing interest as signalling molecules in the pain pathology.Moreover, we succeeded in measuring the activity of CATX, which was substantially increased after L5T.The differential expression of these proteins exhibited the same spatial distribution and temporal progression in the spinal cord, progressing up to the medulla oblongata in the late phase of chronic pain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Animal Physiology, Ruhr-University of Bochum, Bochum, Germany. anna.leichsenring@rub.de

ABSTRACT

Background: Ample evidence suggests a substantial contribution of cellular and molecular changes in the spinal cord to the induction and persistence of chronic neuropathic pain conditions. While for a long time, proteases were mainly considered as protein degrading enzymes, they are now receiving growing interest as signalling molecules in the pain pathology. In the present study we focused on two cathepsins, CATS and CATX, and studied their spatiotemporal expression and activity during the development and progression of neuropathic pain in the CNS of the rat 5th lumbar spinal nerve transection model (L5T).

Results: Immediately after the lesion, both cathepsins, CATS and CATX, were upregulated in the spinal cord. Moreover, we succeeded in measuring the activity of CATX, which was substantially increased after L5T. The differential expression of these proteins exhibited the same spatial distribution and temporal progression in the spinal cord, progressing up to the medulla oblongata in the late phase of chronic pain. The cellular distribution of CATS and CATX was, however, considerably different.

Conclusion: The cellular distribution and the spatio-temporal development of the altered expression of CATS and CATX suggest that these proteins are important players in the spinal mechanisms involved in chronic pain induction and maintenance.

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Related in: MedlinePlus

Behavior and histopathology after L5 transection. A, B: Time course of neuropathic mechanical allodynia in the ipsilateral hind paw expressed as ipsilateral threshold (A) and Diffscore (B, difference between contralateral and ipsilateral withdrawal threshold) in L5T and sham operated animals. The L5T lesion led to a pronounced mechanical allodynia for up to 28 d. C, D: Representative example of ED1-immunostained proximal stump of transected L5 at 14 d after injury. The whole stump is densely filled with ED1-immunopositive macrophages (C) aligning along the trajectory of the axons (D). hab, habituation. Scale bars, 200 μm (C) and 20 μm (D).
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Figure 7: Behavior and histopathology after L5 transection. A, B: Time course of neuropathic mechanical allodynia in the ipsilateral hind paw expressed as ipsilateral threshold (A) and Diffscore (B, difference between contralateral and ipsilateral withdrawal threshold) in L5T and sham operated animals. The L5T lesion led to a pronounced mechanical allodynia for up to 28 d. C, D: Representative example of ED1-immunostained proximal stump of transected L5 at 14 d after injury. The whole stump is densely filled with ED1-immunopositive macrophages (C) aligning along the trajectory of the axons (D). hab, habituation. Scale bars, 200 μm (C) and 20 μm (D).

Mentions: Animals included in the present study fulfilled the following behavioral and anatomical criteria: (i) strong mechanical allodynia measured by the aesthesiometer and defined as an ipsilateral threshold difference between pre- and post-surgery of at least 5 g (Fig. 7A) and a DiffScore (contralateral threshold minus ipsilateral threshold) of a minimum of 5 g (Fig. 7B) and (ii) persistent L5 transsection (short survival times) and/or infiltration of L5 by numerous ED1-immunopositive macrophages (long survival times) (Fig. 7C, D).


Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model.

Leichsenring A, Bäcker I, Wendt W, Andriske M, Schmitz B, Stichel CC, Lübbert H - BMC Neurosci (2008)

Behavior and histopathology after L5 transection. A, B: Time course of neuropathic mechanical allodynia in the ipsilateral hind paw expressed as ipsilateral threshold (A) and Diffscore (B, difference between contralateral and ipsilateral withdrawal threshold) in L5T and sham operated animals. The L5T lesion led to a pronounced mechanical allodynia for up to 28 d. C, D: Representative example of ED1-immunostained proximal stump of transected L5 at 14 d after injury. The whole stump is densely filled with ED1-immunopositive macrophages (C) aligning along the trajectory of the axons (D). hab, habituation. Scale bars, 200 μm (C) and 20 μm (D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2527007&req=5

Figure 7: Behavior and histopathology after L5 transection. A, B: Time course of neuropathic mechanical allodynia in the ipsilateral hind paw expressed as ipsilateral threshold (A) and Diffscore (B, difference between contralateral and ipsilateral withdrawal threshold) in L5T and sham operated animals. The L5T lesion led to a pronounced mechanical allodynia for up to 28 d. C, D: Representative example of ED1-immunostained proximal stump of transected L5 at 14 d after injury. The whole stump is densely filled with ED1-immunopositive macrophages (C) aligning along the trajectory of the axons (D). hab, habituation. Scale bars, 200 μm (C) and 20 μm (D).
Mentions: Animals included in the present study fulfilled the following behavioral and anatomical criteria: (i) strong mechanical allodynia measured by the aesthesiometer and defined as an ipsilateral threshold difference between pre- and post-surgery of at least 5 g (Fig. 7A) and a DiffScore (contralateral threshold minus ipsilateral threshold) of a minimum of 5 g (Fig. 7B) and (ii) persistent L5 transsection (short survival times) and/or infiltration of L5 by numerous ED1-immunopositive macrophages (long survival times) (Fig. 7C, D).

Bottom Line: While for a long time, proteases were mainly considered as protein degrading enzymes, they are now receiving growing interest as signalling molecules in the pain pathology.Moreover, we succeeded in measuring the activity of CATX, which was substantially increased after L5T.The differential expression of these proteins exhibited the same spatial distribution and temporal progression in the spinal cord, progressing up to the medulla oblongata in the late phase of chronic pain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Animal Physiology, Ruhr-University of Bochum, Bochum, Germany. anna.leichsenring@rub.de

ABSTRACT

Background: Ample evidence suggests a substantial contribution of cellular and molecular changes in the spinal cord to the induction and persistence of chronic neuropathic pain conditions. While for a long time, proteases were mainly considered as protein degrading enzymes, they are now receiving growing interest as signalling molecules in the pain pathology. In the present study we focused on two cathepsins, CATS and CATX, and studied their spatiotemporal expression and activity during the development and progression of neuropathic pain in the CNS of the rat 5th lumbar spinal nerve transection model (L5T).

Results: Immediately after the lesion, both cathepsins, CATS and CATX, were upregulated in the spinal cord. Moreover, we succeeded in measuring the activity of CATX, which was substantially increased after L5T. The differential expression of these proteins exhibited the same spatial distribution and temporal progression in the spinal cord, progressing up to the medulla oblongata in the late phase of chronic pain. The cellular distribution of CATS and CATX was, however, considerably different.

Conclusion: The cellular distribution and the spatio-temporal development of the altered expression of CATS and CATX suggest that these proteins are important players in the spinal mechanisms involved in chronic pain induction and maintenance.

Show MeSH
Related in: MedlinePlus