Melior Discovery in vivo models of Pain, Anesthesia and Algesia

in vivo Efficacy: Animal Models

Melior is a leading contract research provider of preclinical in vivo pharmacology services using rat and mouse models of Pain, Anesthesia and Algesia.

Mechanisms of Pain

Melior has established a broad array of preclinical analgesic models including rodent models of acute pain and chronic neuropathy. Many of these models are a staple part of Melior’s theraTRACE® platform. As a result we have been running these models for many years and run these models routinely.

Neuropathic and Pain Models

Algesia Assays and Models

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Migraine Model

Headache disorders consistently rank as one of the most prevalent neurological conditions globally, with migraine being one of the most disabling disorders. Though the mechanism of migraine is complex and unresolved, one hypothesis states repeated activation of the trigeminal vascular system leads to long-term physiological changes. Clinical symptoms include trigeminal allodynia and sensitivity to nitrates, both resulting in pain.

Proportional effects on periorbital von Frey thresholds relative to pretreatment baseline.

After four weeks of prostaglandin infusions directly onto the dura, rats exhibit chronic periorbital allodynia and nitrate sensitivity measured by mechanical von Frey fibers. Following infusion, rats are challenged with vehicle-only, glycerol trinitrate (GTN) and vehicle, or GTN and a potent vasoconstrictor.

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IBS Model and Acetylcholine Writhing Assay

Irritable Bowel Syndrome (IBS) is a syndrome that is expressed as abdominal cramping, gastrointestinal pain and disturbances in GI transit. These conditions are produced by colonic spasticity and irregular contractility. The disturbances in GI transit can be modeled by examining expulsion of a colonically-inserted glass bead. The cramping and pain component of IBS can be modeled by injecting acetylcholine into the peritoneum of mice. IP administered ACh promotes smooth muscle contractility and can be monitored, in animals, by quantifying the writhing response. In this study, the acetylcholine writhing response was validated as a model of smooth muscle contractility and visceral pain. This model was validated using a reference anti-nociceptive compound.

Data illustrating that this IBS model may be useful for identifying test agents that have therapeutic potential for treating abdominal discomfort

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Chronic Constrictive Injury

The chronic constriction injury (CCI) model is induced by ligation to the sciatic nerve. Melior has experience in developing several versions, including partial and complete sciatic nerve ligation models. The CCI model induces a neuropathic pain response that can be detected by von Frey mechanical thresholds and Hargreaves thermal sensitivity, and can be attenuated by administering analgesics for neuropathic pain.

Von Frey mechanical thresholds of mice treated with gabapentin or vehicle during the CCI model.

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Formalin Analgesia Assay

The formalin chemical nociception assay is a commonly used analgesia assay that is typically included in a battery of analgesic tests. Formalin produces a painful irritation when injected into the skin of experimental animals that can be measured as a licking response. Formalin induced chemical nociception can be attenuated by classical anti-nociceptive agents including opiods and GABA enhancers. We include the formalin assay in a battery of analgesia assays that include the thermal nociceptive assay and the touch sensitivity assay.

More Models Available! See All Models

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