Spinal Nerve Ligation Model

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Peripheral nerve injury, due to trauma, disease or various sources of toxicity is a cause of chronic pain. This pathology can be readily modeled in rodents with a number of neuropathic pain models that Melior has developed.

L5 spinal nerve ligation has been demonstrated to increase sensitivity of the rat hind paw and is commonly used as a model of neuropathic pain and allodynia. This assay assesses the sensitivity and pain responses of L5 ligated rats to thin hair-like filaments of varying diameter and corresponding force needed to bend the fiber.

Von Frey filaments are typically used to ascertain the mechanoreceptor threshold and the ability of a test agent to affect the mechanoreceptor response. Alternatively, allodynia can be evaluated by monitoring for thermal sensitivity using methods such as the Hargreaves test in the SNL model.

The studies described below illustrate the validation of the SNL model in rats using Von Frey filaments to monitor mechanical sensitivity.

Gabapentin-treated SNL model rats. L5 spinal nerve ligation surgery induced well-developed hind paw hypersensitivity two weeks post surgery. Gabapentin treated rats had significantly higher thresholds to pain caused by von Frey filaments at 1 and 3 hours post dosing. Vehicle treated rats showed no difference in sensitivity post dosing compared to baseline measurements. Data are mean ± SEM (n=14/group); *p<0.05 compared to vehicle.

Morphine-treated SNL model rats. L5 spinal nerve ligation surgery induced well-developed hind paw sensitivity two weeks post surgery. Morphine treated rats had significantly higher thresholds to pain caused by von Frey filaments at 0.5 hours post dosing. Vehicle treated rats showed a slight increase in sensitivity (lower threshold) post dosing compared to baseline measurements. Data are mean ± SEM (n=8/group); *p<0.05 compared to vehicle.

The SNL Model of neuropathic pain is normally only conducted in rats because of the challenges associated with performing this surgery in mice. Animals are used for testing 2 weeks after surgery and can be used for up to 2-3 months afterwards.