Maropitant – the unveiling of an analgesic effect?
In previous posts and a webinar we have used the literature to clarify the fact that maropitant does not have a demonstrated analgesic benefit in dogs. One of the early studies that suggested there could be an advantage was work by Boscan et al (2011) that demonstrated a MAC sparing effect. Now, analgesics are one factor that reduces MAC, but not the only consideration. The mechanism of action of NK-1 inhibition makes us think that there should be a benefit.
In a 2026 paper, Figueirinhas et al report the following findings which is summarised in their abstract below;
This prospective, randomized, blinded clinical study aimed to compare the intraoperative and postoperative analgesic effects of maropitant versus methadone in female dogs undergoing elective ovariohysterectomy and to evaluate whether maropitant facilitates ovarian ligament exteriorization, potentially through modulation of visceral tone. Seventy-two healthy bitches were randomly assigned to receive dexmedetomidine with either methadone (Group M, n = 34) or maropitant (Group MAR, n = 38). In addition to assessing intraoperative cardiorespiratory parameters and anesthetic requirements, postoperative pain was evaluated using the CMPS-SF scale. Exteriorization of the ovaries was scored by the surgeon. Maropitant-treated dogs showed higher HR and RR during ovarian traction, easier ovary exteriorization, lower postoperative pain scores at 0, 1, and 2 h, and reduced need for rescue analgesia. These findings suggest that maropitant provides effective analgesia and may modulate visceral tone, facilitating surgical manipulation and enhancing patient comfort.
Let’s dig into this. For starters, the paper was published in The Veterinary Journal, a highly reputable journal with a rigorous review process. This gives us confidence in the science.
The model is a tough one – ovarian ligament exteriorisation. This is a part of the ovariohysterectomy surgery guaranteed to stimulate a nocifensive response. In their introduction the authors state;
‘Regardless of the technique, traction and ligation of the ovarian pedicles is considered
the most painful phase of the procedure.’
The numbers – are 72 subjects, 34 and 38 in each group a suitable number? We need to review the manuscript in detail and see if a sample size calculation was performed. The authors make the following statement at the end of their introduction;
Furthermore, the sample size used here is among the largest reported in this context, providing sufficient statistical power to detect clinically relevant differences.
This is technically a result and does not have a place in the introduction. The inclusion here does make us question the reviewers and the editorial oversight.
Whilst the authors do state that an a priori sample size calculation was conducted, they do not state the primary outcome measure. So we are not sure whether this was based on pain scores or the surgeon score for ovarian exteriorisation. I feel the reviewers should have been more rigorous in their assessment and requested the inclusion of this information.
The drug combination. Dexmedetomidine 3mcg/kg IM was administered either with methadone 0.2 mg/kg IM or with maropitant 1 mg/kg SC. That’s a hefty comparison – methadone versus maropitant. And we have to ask, with no proof prior to this study that maropitant is analgesic, the reliance for analgesia in these cases is solely on the dexmedetomidine – where we know analgesia is dose dependent and short acting. The dose of dexmedetomidine was 3 mcg/kg IM which is unlikely to contribute a significant analgesic effect given the dose and the route of administration. The rescue protocol was fentanyl 0.025 mg/kg (25mcg/kg) IV in response to HR or MAP increases >25% of values recorded in the preceding 5 minutes. This is a huge dose of fentanyl and I question the influence this had on subsequent nociception – a much more common dose would be 1-2 mcg/kg which would allow for assessment of further nociception. I suspect this high dose of fentanyl would influence the response to exteriorisation of the second ovary.
The evaluation was comprehensive and as expected for an acute pain study. The outcome measures included response to stimulus, additional analgesic requirement intra and post-operatively and pain scores post-operatively. A pain scale was used – the Colorado State Pain Scale – although this is not fully validated and we question why a validated pain scale was not chosen.
So, we have scrutinised the methods to ask ourselves whether we think the study is set up to produce the conclusions that are stated.
On to the results. What do we make of this?
Maropitant-treated dogs showed higher HR and RR during ovarian traction, easier ovary exteriorization, lower postoperative pain scores at 0, 1, and 2 h, and reduced need for rescue analgesia.
Why were the HR and RR higher in maropitant treated dogs? Higher HR and RR suggest nociception, but that doesn’t quite fit with ease of ovarian exteriorisation. My alternative thoughts are that in the methadone group, the methadone was doing what we expect of opioids, and reducing HR. Although I might expect the dexmedetomidine to be the predominant HR reducing drug in these cases. Lower post-operative pain scores do certainly support an analgesic benefit, although I am surprised that these are lower than the methadone scores. To judge whether this is significant we need to look back at the sample size calculation. Was that calculation based on pain scores as the outcome measure? If it was not, then we cannot place so much weight on this as the defining difference between the two groups. Lower post op pain scores will translate directly into a reduced need for rescue analgesia.
Even before we read the full paper – and you can see from the above that we must read the full paper – we already have some doubts based on what we see so far and in the conclusion statement;
These findings suggest that maropitant provides effective analgesia and may modulate visceral tone, facilitating surgical manipulation and enhancing patient comfort.
Suggest = not confirmed, further work required
May modulate = we don’t 100% know
Reviewers are very good at ensuring the reported conclusions are in line with the results provided and I am sure this is the case here.
What would I really like to see?
Would the combination of methadone, maropitant and dexmedetomidine confer an advantage? I suspect many of you are already using this combination (with either dexmedetomidine or medetomidine).
Bottom line – should we add maropitant to our anaesthetic protocol as a pain adjunct? I feel we are seeing another maropitant paper that on the surface appears to suggest an analgesic benefit, but when you dig a little deeper, the reality is less clear.
Most of the above point is based on this specific paper. A further paper of interest is by Ramirez-Castillo et al (2026) which examines the use of a maropitant infusion and compares this to a lidocaine infusion in dogs undergoing OVH. The maropitant dose was 1mg/kg + 100mcg/kg/min. That equates to 6mg/kg/hr. It therefore appears that perhaps it is dose we should be looking at. In this study a benefit was demonstrated using a parasympathetic tone monitor. Whilst running a CRI will be practical for some, there is also the cost of the high dose maropitant to consider.
References
Boscan P, Monnet E, Mama K, et al. (2011). Effect of maropitant, a neurokinin 1 receptor antagonist, on anesthetic requirements during noxious visceral stimulation of the ovary in dogs Am J Vet Res. 72(12):1576-9.
Corrêa JMX, Soares PCLR, Niella RV, et al. (2019) Evaluation of the Antinociceptive Effect of Maropitant, a Neurokinin-1 Receptor Antagonist, in Cats Undergoing Ovariohysterectomy. Vet Med Int. 2019 Apr 8;2019:9352528.
Marquez M, Boscan P, Weir H, et al. (2015) Comparison of NK-1 Receptor Antagonist (Maropitant) to Morphine as a Pre-Anaesthetic Agent for Canine Ovariohysterectomy. PLoS One. 10(10):e0140734.
Pedro F, Raquel R, Cristian A, Kseniia I, Miguel B. Evaluation of maropitant's analgesic and tissue relaxation effects during ovariohysterectomy in bitches. Vet J. 2026 Aug;318:106739. doi: 10.1016/j.tvjl.2026.106739. Epub 2026 Jun 10. PMID: 42270044.
Ramírez-Castillo A, Interlandi C, Miranda Cortés AE, Ziaei-Darounkolaei N, Casas-Alvarado A, Jiménez-Yedra A, Hernández-Avalos I. Assessment of Maropitant Citrate Effectiveness as an Intraoperative Analgesic Through Monitoring Parasympathetic Tone Activity in Female Dogs Undergoing Ovariohysterectomy. Vet Sci. 2026 May 10;13(5):463. doi: 10.3390/vetsci13050463. PMID: 42188933; PMCID: PMC13211541.
Comments