Ligation of mouse L4 and L5 spinal nerves produces robust allodynia without major motor function deficit.
Spinal nerve L5/L6 ligation (SNL) in rats has become the standard for mechanistic studies of peripheral neuropathy and screening for novel analgesics. Conventional SNL in our hybrid mice resulted in a wide range of allodynia. Anatomical evaluation indicated that a variable number of lumbar vertebrae existed, resulting in L4/L5 or L5/L6 being ligated. Surprisingly, L4/L5 ligation did not result in ipsilateral hind limb paralysis and produced robust allodynia. Following a recent report that the mouse L4 neural segment is homologous with rat L5 we generated L4, L5 or both L4 and L5 (L4/L5) ligations in C57 mice after establishing a modified set of surgical landmarks. In contrast to rats, L4 ligation in these mice did not result in hind limb paralysis. Robust allodynia was observed in all three ligation groups. Nerve degeneration confirmed that L4 and L5, respectively, are primary contributors to the tibial and sural branches of the sciatic nerve in mice. A larger von Frey sensitive area reflected the wider distribution of Wallerian degeneration in the hindlimb of L4- compared to L5-ligated mice. Ligation of mouse L4 and L5 spinal nerves produces consistent, robust neuropathic pain behaviors and is suitable as a model for investigating mechanisms of neuropathic pain and for testing of novel analgesics. Gabapentin, used as a validation drug in neuropathic pain models and as a reference compound for novel analgesics, significantly reduced allodynia in the mice tested (L4/L5 ligations). Given the ease of surgery, robust allodynia, and larger von Frey sensitive area, we conclude that combined ligation of spinal nerves L4 and L5 optimizes the SNL model in mice.
Neuroscience Research, Lexicon Pharmaceuticals Inc., The Woodlands, TX 77381, USA.
Gui-Lan
GL
Ye
Neuroscience Research, Lexicon Pharmaceuticals Inc., The Woodlands, TX 77381, USA.
Katerina V
KV
Savelieva
Neuroscience Research, Lexicon Pharmaceuticals Inc., The Woodlands, TX 77381, USA.
Peter
P
Vogel
Neuroscience Research, Lexicon Pharmaceuticals Inc., The Woodlands, TX 77381, USA.
Kevin B
KB
Baker
Neuroscience Research, Lexicon Pharmaceuticals Inc., The Woodlands, TX 77381, USA.
Sara
S
Mason
Neuroscience Research, Lexicon Pharmaceuticals Inc., The Woodlands, TX 77381, USA.
Thomas H
TH
Lanthorn
Neuroscience Research, Lexicon Pharmaceuticals Inc., The Woodlands, TX 77381, USA. Electronic address: indrani.rajan@lonestar.edu.
Indrani
I
Rajan
D000588:Amines / Q000627:therapeutic use; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D000077206:Gabapentin; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D008026:Ligation; D008297:Male; D051379:Mice; D009048:Motor Skills / Q000502:physiology*; D009410:Nerve Degeneration / Q000150:complications / Q000473:pathology; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D010264:Paraplegia; D013127:Spinal Nerves / Q000473:pathology* / Q000601:surgery; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
Mouse neuropathic pain; Neurogenic atrophy; Spinal nerve ligation; Tactile allodynia; Wallerian degeneration; von Frey