Chronic Constriction Injury (CCI)
A peripheral nerve injury model for neuropathic pain.
Standard Chronic Constriction Injury (CCI)
In the standard CCI model, the left sciatic nerve is ligated causing inflammation, swelling, and ultimately, peripheral pain. This method results in a severe and disproportional reduction of large myelinated fibers. Although significant disruption of small unmyelinated C-fibers occurs as well, many remain intact. For this reason, pain behaviors and increased sensitivity to stimuli is observed following surgery.
Enhanced CCI model
In our enhanced model, the left sciatic nerve is exposed in anesthetized animals above the femoral joint. One loose silk suture knot and 3 cat gut sutures are applied to the sciatic nerve. The skin is then clamped closed. One week later, the animals' pain threshold is assessed using the von Frey filament test. Animals that demonstrate reduced threshold in the operated leg are included in the study and divided into different treatment groups. The pain threshold is then re-assessed following compound dosing.
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Mouse CCI Model
Standard Study Outline:
- Species: C57bl/6 mice
- CCI operation on day 0
- withdrawal assessment starting on day 7
- Readouts: von Frey, response to cold
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Rat CCI Model
Standard Study Outline:
- Species: SD rats
- CCI operation on day 0
- Withdrawal assessment starting on day 7 or 8
- Readouts: von Frey, respond to cold
- Study duration up to 11 - 23 day
Assessments
Neurological disorders often result in a combination of motor and cognitive deficits. Thus, behavioral assessments in conjunction with physiological readouts offer a broader understanding of the basic biological mechanism of disease and cognitive impairment, highly relevant to therapeutic developments.
Behavior
Pain behavior tests assess the response to various pain stimuli.
Biomarkers
Evaluate pro-inflammatory, anti-inflammatory, and translational biomarkers from CSF samples.
Histology
IHC and histological staining to evaluate inflammatory markers in the paw skin.
Electrophysiology
Evaluate spontaneous nerve firing using in vivo electrophysiology.
Scientific Data
Data shows gabapentin response in the von Frey behavior test in the CCI model.
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Peripheral Nerve Injury Datasheet
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