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
-
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.
-
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.
-
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.
-
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).
-
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.
Species: Rat
Length: 14-15 days
Assessments: Von Frey, Dynamic Weight bearing, Electrophysiology (cAMP, dSEP and spontaneous activity)
-
Nerve Block
Nerve blocking agents are often used to replace general anesthesia in surgery, provide effective post-operative pain control, and reduce opioid-related side effects. The preclinical model of sciatic nerve block enables researchers to directly access and dose to the sciatic nerve and allows the screening of new nerve blocking agents or drugs designed to reverse local analgesia.
-
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 morphine and gabapentin 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
IENF Staining
Intraepidermal nerve fiber (IENF) analysis in skin biopsy samples has become a standard clinical tool in diagnosing neuropathies in patients. Focused on using clinically relevant assessments in preclinical studies, MD Biosciences offers IENF analysis in its studies. Data shows IENF staining in the pig model of peripheral neuropathy.

Pain Response
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. Data shows Von Frey and Cold Plate tests in the CCI model in rats.
