The tail-immersion pain model is a well-known approach in the exploration of thermally-evoked acute pain. Its design is intricately woven around ‘spinal’ mechanisms, making it particularly insightful for central opioid-related targets. The induction process of this model involves the submersion of the distal portion of the tail in a controlled warm water bath. A pivotal metric of this procedure is the duration it takes for a reflexive tail withdrawal, capturing both the pain threshold and its subsequent response.

When outlining the standard study design at NuChem, our research typically encompasses 4-6 distinct experimental groups. Each of these groups comprises 6-8 subjects to ensure both robust data collection and statistical validity. Opioids, due to their pronounced efficacy, often serve as the primary positive controls in this model. However, it’s essential to note that these controlled substances are subject to testing at NuChem only upon obtaining an exemption license from Health Canada. Other analgesics often yield suboptimal effects in this model, emphasizing the model’s keen specificity towards central opioid mechanisms.

For consistent and reproducible outcomes in our investigations, the model at NuChem is meticulously validated for the C57BL6 mouse species.

After rigorous evaluation of the tail-immersion pain model, 50°C emerged as the optimal temperature for eliciting discernible and consistent pain responses. This temperature was meticulously selected to balance the fine line between inducing a perceptible nociceptive reaction and ensuring the well-being of the test subjects.

A suite of four drugs – Duloxetine, Mexiletine, Diclofenac, and Gabapentin – were tested within this framework. As expected, none of these drugs could produce any meaningful analgesic effects in this model which is more sensitive to centrally acting opioid drugs, as discussed earlier. Of the cohort, Gabapentin demonstrated notable effects, but only at a dosage of 300 mg/kg. It’s pivotal to underscore, however, that alongside these effects, there were concomitant adverse reactions observed at this dose level of Gabapentin. The findings, particularly the nuanced response with Gabapentin, emphasize the critical balance between therapeutic potential and safety considerations in drug evaluations.