Pilot Study Evaluates Non-Opioid Analgesic Opiranserin for Surgical Pain Relief in Dogs

Opiranserin operates through two primary mechanisms at the spinal cord level. It inhibits glycine transporter 2, enhancing the spinal cord's natural pain suppression signals, and blocks the serotonin 5-HT2A receptor, which mitigates the pain signals sent from the brain. This drug does not have sedative effects as it does not act through sedation pathways.

In human studies, opiranserin has shown potential by reducing opioid use by approximately 30% after abdominal surgeries in Phase 2 and 3 clinical trials. Prior to this study, its use in veterinary medicine had been limited to a study using a nociception model in healthy dogs.

In this study, eight healthy intact male Beagles were randomly assigned to receive either an opiranserin infusion (loading dose of 5 mg/kg/h for one hour followed by 0.33 mg/kg/h for nine hours) or saline. All dogs were induced with alfaxalone and maintained on isoflurane, with meloxicam administered. No opioid premedication or local blocks were utilized to isolate the effects of opiranserin.

During surgery, blood pressure and heart rate were monitored across 11 surgical events. If either parameter increased by 20% or more, the dogs were given remifentanil as a rescue analgesic. Post-surgery pain was assessed hourly for about seven hours using the Glasgow Composite Measure Pain Scale–Short Form.

Results indicated that dogs receiving opiranserin needed a median of 2 rescue doses during surgery, while those in the saline group required a median of 6.5 doses. All saline-treated dogs required more rescues than any dog treated with opiranserin, particularly at the exteriorization of the first testis, a notably painful part of the procedure, where all saline dogs needed rescue doses but only one dog in the opiranserin group did.

Following surgery, dogs on opiranserin showed lower pain scores at the first hourly evaluation, approximately 1.5 hours after extubation, though scores were similar at later evaluations. Overall blood pressure and heart rate responses were also lower in the opiranserin group, although significance was not established after statistical correction.

Adverse effects were minimal; only one dog in each group experienced vomiting and nausea, making it unclear if these reactions were related to the drug. There was no indication that opiranserin worsened anesthesia-related low blood pressure.

The authors caution that the findings are preliminary and should be interpreted with care. With only four dogs in each group, the absence of a positive control, lack of plasma drug measurements, and a protocol that bypassed standard multimodal analgesia limit direct application to clinical practice. They noted that castration generally results in mild postoperative pain, making significant differences harder to detect. As the dosing regimen is still investigational, it is not yet an established clinical treatment.

Despite opioids being the mainstay for perioperative pain management, their side effects and ongoing supply and regulatory challenges drive the need for alternatives. While early findings from this first clinical study of opiranserin in companion animals are promising, further research with larger samples is necessary.