129: Perioperative Analgesic Effects of Opiranserin in Canine Castration

Topic: Basic Science
Subtopic: Pain category (ICD-11), Acute postsurgical pain, , , , , , , , , , Pharmacological interventions, Drug development

Background and Aims: Opiranserin (VVZ-149) is a novel analgesic combining glycine transporter 2 (GlyT2) inhibition and 5-hydroxytryptamine 2A (5-HT₂A) receptor antagonism, targeting central sensitization pathways underlying both nociception and pain hypersensitivity. These dual mechanisms are relevant to both intraoperative nociception and postoperative pain under general anesthesia. Clinical studies in humans have validated opiranserin's analgesic efficacy for postoperative pain management following laparoscopic abdominal surgery. However, its potential to suppress intraoperative nociception, and whether its analgesic effects extend across species, has not been evaluated. Castration in male dogs is a common procedure associated with significant intraoperative nociceptive responses and postoperative pain, providing a clinically relevant model for assessing both cross-species analgesic efficacy and intraoperative pain suppression. This study aimed to evaluate whether continuous rate infusion (CRI) of opiranserin reduces intraoperative rescue analgesia requirements and improves postoperative pain outcomes in male dogs undergoing castration under isoflurane anesthesia.

Methods: Eight male Beagle dogs were assigned to a normal saline (N/S) group (n = 4) or an opiranserin group (n = 4). Opiranserin was administered as a CRI (5 mg/kg over 1 hour, then 3 mg/kg for 9 hours). The N/S group received an equivalent volume. Intraoperative rescue analgesia (remifentanil 5 μg/kg intravenously) was administered when ≥ 2 of 3 variables, mean arterial pressure (MAP), heart rate (HR) and respiratory rate (RR), increased ≥ 20% from baseline. Postoperative pain was assessed using Glasgow Composite Measure Pain Scale–Short Form (GCMPS-SF, 0–20) at 30 minutes post-extubation (T0) and hourly to 7 hours (T7; CRI discontinuation at T8), with rescue analgesia at scores ≥ 5. Changes in (Δ) MAP, HR, and RR across 11 surgical events were analyzed by linear mixed model. Rescue frequency, time to first rescue, GCMPS-SF scores, and adverse effects were compared by Mann-Whitney U test.

Results: The N/S group required significantly more intraoperative rescue analgesia than the opiranserin group (median 6.5 [range 3–9] versus 2 [range 2–2], p = 0.021), reflecting consistent nociceptive suppression throughout surgery. Time to first rescue did not differ significantly between groups (N/S: median 1.27 minutes [range 1.00–2.25]; opiranserin: median 2.58 minutes [range 1.25–5.55]; p = 0.194). Linear mixed model analysis identified significantly greater vital sign changes in the N/S group at first testis exteriorization: ΔMAP (β = 24.4 mmHg), ΔHR (β = 27.0 beats/minute), and ΔRR (β = 20.2 breaths/minute), all p ≤ 0.003, indicating attenuated nociceptive reactivity in the opiranserin group. Postoperative GCMPS-SF scores did not differ significantly between groups at any timepoint from T0 through T8, with all scores remaining below the rescue threshold in both groups. Adverse effects including vomiting, nausea, and lip-smacking were comparable between groups, and no significant differences were detected (all p > 0.05).

Conclusions: Opiranserin significantly reduced intraoperative rescue analgesia requirements in dogs undergoing castration, with the opiranserin group requiring substantially fewer remifentanil interventions compared to controls (median 2 versus 6.5). Concurrent attenuation of vital sign responses at first testis exteriorization further supports its intraoperative analgesic efficacy. Although postoperative GCMPS-SF scores did not differ significantly between groups, this may reflect limited statistical power due to the small sample size. No adverse effects were observed in either group, supporting the safety of opiranserin at the doses administered. These newly completed findings provide timely cross-species evidence of opiranserin's intraoperative pain-suppressing potential, complementing its established analgesic efficacy in human postoperative settings. Collectively, this evidence provides a basis for opiranserin as a non-opioid analgesic adjunct across perioperative contexts and species, and supports further investigation of its intraoperative analgesic utility in human surgical patients.

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Presenting Author: Seongwon Lee
Submitting Author: Won-gyun Son

Senior Author: Won-gyun Son

IASP 2026 Global Year theme of Neuropathic Pain: No

• Seongwon Lee: DVM - Seoul National University
• Seonbin Oh: DVM - Seoul National University
• Inhyung Lee: DVM, PhD - Seoul National University
• Won-gyun Son: DVM, PhD - Seoul National University