Fraunhofer Institute for Cell Therapy and Immunology IZI
Fraunhofer Institute for Cell Therapy and Immunology IZI

Neuropathic pain in rats

Species

Rat

Fields of application

In the Spinal Nerve Ligation (SNL) model of neuropathic pain one or optionally two spinal nerves (L5 and L6) are tightly ligated and (also optionally) are cut in a surgery. This unilateral intervention leads to allodynia and hyperalgesia in one dermatome of the ipsilateral hind paw. One major advantage of the SNL model over other surgical models of neuropathic pain is the fast occurrence of clinical symptoms already one day after intervention. Assessment of clinical symptoms is performed by means of e.g. Dynamic Plantar Aesthesiometer, von Frey filaments (both mechanical allodynia) or the Plantar test (thermal hyperalgesia).

  • Pharmacodynamics and pharmacokinetics
  • (Patho)physiological processes
  • Therapeutic efficacy
  • Proof of concept

Endpoints / outcome parameter

  • Clinical symptoms (mechanical allodynia, thermal hyperalgesia; in vivo)
  • Immune cells in full blood (in vivo)
  • Cytokines and others in blood plasma (in vivo)
  • Neuroinflammation (spinal nerves, spinal cord, brain; ex vivo)

Readout parameter

  • Assessment of neuropathic pain symptoms (von Frey test, Plantar test)
  • Flow cytometry
  • ELISA / CBA (cytometric bead array)
  • RT-PCR
  • Western Blot
  • Histology (various classical histological stains)
  • Immunohistochemistry

Quality management and validation

  • Controls
  • Blinded induction
  • Blinded data collection and analysis
  • Randomisation
  • Allocation concealment
  • Biometric expertise
  • Internal quality management

References

Leichsenring A, Bäcker I, Wendt W, Andriske M, Schmitz B, Stichel CC, Lübbert H. Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model. BMC Neurosci. 2008; 9:80

Leichsenring A, Andriske M, Bäcker I, Stichel CC, Lübbert H. Analgesic and antiinflammatory effects of cannabinoid receptor agonists in a rat model of neuropathic pain. Naunyn Schmiedebergs Arch Pharmacol. 2009; 379(6):627-36

Leichsenring A. Das L5T Modell für neuropathischen Schmerz – Untersuchungen zur Rolle der zentralnervösen Entzündungsreaktion. Südwestdeutscher Verlag für Hochschulschriften (SVH) 2009; ISBN: 978-3-8381-0572-7

Assessment of neuropathic pain symptoms and histopathology after SNL (=L5T) surgery (from: Leichsenring et al., 2008). 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 (= surgery without nerve injury) animals. The L5T lesion led to a pronounced mechanical allodynia for up to 28 days. C+D: Representative example of ED1-immunostained proximal stump of transected spinal nerve at 14 days 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).
© Fraunhofer IZI
Assessment of neuropathic pain symptoms and histopathology after SNL (=L5T) surgery (from: Leichsenring et al., 2008). 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 (= surgery without nerve injury) animals. The L5T lesion led to a pronounced mechanical allodynia for up to 28 days. C+D: Representative example of ED1-immunostained proximal stump of transected spinal nerve at 14 days 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).