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
- Chronic Constrictive Injury Model
- Diabetic Neuropathy Model
- IBS Model and Acetylcholine Writhing Assay Migraine Mode
- Spinal Nerve Ligation Model
- von Frey / Carrageenan Allodynia Assay
Algesia Assays and Models
Migraine Headache – Inflammatory Cocktail 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.
After the 5d inflammatory soup sensitization period, rats had a one-week wash-out period and were then challenged with 0.1mg/kg glyceryl trinitrate (GTN), followed by sumatriptan, vehicle, or Viridian Pharmaceutical’s proprietary topical formulation of CBD, with at least a one-week washout between each treatment.
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.
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.
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.
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