Peripheral Nerve Injury
Preclinical models for assessing neuropathic pain as a result of injury to the nerve.
Understanding Mechanisms underlying Neuropathic Pain
Neuropathic pain may arise from many different disease states and present with a variety of symptoms, including shooting or burning pain, tingling, numbness, and allodynia (pain in response to a normally innocuous stimulus). Clinically significant relief is often difficult to achieve, in part because conventional opioid therapy is typically less effective for neuropathic pain. Also, patients vary widely in their response to other types of analgesics. Understanding the mechanisms underlying neuropathic pain syndromes is crucial to the development of more effective therapies.
Models of Peripheral Nerve Injury
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Spinal Nerve Ligation (SNL)
In the SNL model of peripheral neuropathy, the L5 and L6 spinal nerves are isolated and can either be cut or tightly ligated with surgical silk. Axonal degeneration occurs, with all types of axons being approximately equally affected. Pronounced mechanical allodynia follows, accompanied by spontaneous pain behaviors, cold allodynia, which lasts for months with no recovery.
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Chronic Constriction Injury (CCI)
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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Sciatic Nerve Crush
Neuropathic pain may arise from many different disease states and present with a variety of symptoms, including shooting or burning pain, tingling, numbness, and allodynia, Clinically significant relief is often difficult to achieve, in part because conventional opioid therapy is typically less effective for neuropathic pain. Understanding the mechanisms and underlying neuropathic pain syndromes is crucial to the development of more effective therapies.
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Sciatic Nerve Cuff
The mouse nerve cuff model is based on a compression of the sciatic nerve using a polyethylene cuff that is implanted around the main branch of the sciatic nerve. This model produces more consistent pain with less variability than other mouse models of peripheral nerve injury (PNI).
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Stretch-induced Nerve Injury
Models of nerve injury are useful in evaluating compound effects on nerve regeneration. The stretch model is a model of nerve injury that involves a later onset of functional recovery compared to the crush model.
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Spared Nerve Injury
The Spared Nerve Injury (SNI) model is a partial denervation model, in which the common peroneal and tibial nerves are injured, producing consistent and reproducible tactile hypersensitivity in the skin territory of the spared, intact sural nerve.
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Distal Tibial Injury (DTI)
In the distal tibial injury model, the tibial nerve is dissected and severed as close to its distal end as possible, ensuring avoidance of the popliteal vessels. This model directly reflects this clinical reality, ensuring its relevance and practicality in real-world scenarios.
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Surgically-induced Peripheral Neuritis Translational Model
Preclinical rodent models largely contribute to our understanding of chronic neuropathic pain, however these animal models are limiting due to poor clinical translation. Since pigs share similarities with humans, such as skin innervation and neurological resemblance, MD Biosciences Neuro developed a pig model for chronic pain caused by surgically-induced peripheral neuritis (PNT) (Castel et al., 2016). In the model, 75% of animals exhibit mechanical and tactile allodynia by day 28 post surgery, demonstrating painful neuropathy. We also showed that positive controls inhibited hypersensitivity to von Frey filaments and feather stimuli, reversing spontaneous pain-related behavior in a dose-related manner.
Click here for more information on the translational pig model of PNT
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 and anti-inflammatory 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 dynamic weight bearing in the CCI model.
Review the complete dataset.
Peripheral Nerve Injury Datasheet
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