Rat Partial Sciatic Nerve Ligation

Induction: 

Prior to surgery animals will be given meloxicam (1mg/kg PO) for pain management. On study day 0, animals will be deeply anesthetized with isoflurane and the thigh area of the left leg will be shaved and surgically prepped by wiping the area with betadine and alcohol (70% isopropyl). Instruments will be sterilized using a bead sterilizer between animals. The prepped leg will be placed through a sterile surgical drape for the surgery. An incision will be made in the skin (approximately 1cm for rats and 0.5cm for mice) and the muscle will be blunt dissected to expose the sciatic nerve near the trochanter just distal to the point at which the posterior biceps semitendinosus nerve branches off the common sciatic nerve. For sham animals the sciatic nerve is left intact and the muscle is sutured and the skin closed with staples. For partial sciatic nerve ligation animals, the nerve is carefully freed and one-third to one-half of the nerve is tightly ligated with an 8-0 silk suture. The wound is then closed as in sham-operated animals. Animals may be given subcutaneous saline to aid in post-surgical recovery.

Post-operative care will include placing the animal in a clean cage on a heating pad for recovery and placing food on the bottom of the home cage for easy access. Animals will be checked daily, per the IACUC-approved post-operative monitoring plan. Approximately one-week post surgery skin staples will be removed. Studies will last no longer than six weeks post surgery.

Disease Parameters/Progression: 

Baseline behavioral testing may be done prior to surgery. On study day 0 animals will undergo surgery. Approximately one-week post surgery skin staples will be removed. One week post surgery animals will be assessed and enrolled in the study. Animals exhibiting signs of limb dysfunction (i.e., dragging the leg) will not be included in the study and euthanized. Administration of experimental test articles may occur at any point following acclimation of the animals to the facility, depending on sponsor request. Animals will be observed daily for post administration signs of overt toxicity due to compound treatment throughout the course of the study.

Dosing Paradigms:

Route of administration: SC, PO, IP, IV

Clinical Assessment:

Body weights, gait assessment, von Frey testing, and an elevated ladder test will be performed to monitor pain. Studies will last no longer than six weeks post surgery.

Sample Data (Click on Image to Enlarge):

Mouse Clinical

Rat Clinical

Pain Data

Notes:

Optional Endpoint

  • PK/PD blood collections
  • Cytokine/chemokine analysis via Luminex(R)
  • Other sandwich ELISAs
  • CBC/clinical chemistry analysis
  • Soft tissue collection
  • Histopathologic analysis
  • Immunohistochemistry analysis

References

 

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  2. Dowdall T, Robinson I, and Meert TF. Comparison of five different rat models of peripheral nerve injury. Pharmacology, Biochemistry, and Behavior. 2005; 8:93-108.
  3. Kim KJ, Yoon YW, and Chung JM. Comparison of three rodent neuropathic pain models. Exp Brain Res. 1997; 113:200-206.
  4. Seltzer Z, Dubner R, and Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injuey. Pain. 1990; 43:205-218.
  5. Pacharinsak C and Beitz A. Animal models of cancer pain. Comparative Medicine. 2008; 58(3):220-233.
  6. Takaishi K, Eisele JH, and Carstens E. Behavioral and electrophysiological assessment of hyperalgesia and changes in dorsal horn responses following partial sciatic nerve ligation in rats. Pain. 1996; 66:297-306.
  7. Nakamura Y, et al. Neuropathic pain in rats with a partial sciatic nerve ligation is alleviated by intravenous injection of monoclonal antibody to high mobility group box-1. PLoS ONE. 2013.
  8. Malmberg AB and Basbaum AI. Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates. Pain. 1998; 76:215-222.
  9. Xu M, et al. Sciatic nerve ligation-induced proliferation of spinal cord astrocytes is mediated by κ opioid actiation of p38 mitogen-activated protein kinase. The Journal of Neuroscience. 2007; 27(10):2570-2581.
  10. Fish R, et al. Anesthesia and Analgesia in Laboratory Rodents. 2011.

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