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Antinociceptive effects of subcutaneous butorphanol administration in healthy horses.
Abstract: Subcutaneous (SQ) butorphanol administration maintains target plasma concentrations in horses longer than intravenous administration with fewer adverse effects. This study aimed to evaluate whether SQ butorphanol also produces clinically relevant antinociception in healthy horses. Unassigned: In a blinded, randomized, cross-over study, eight horses received 0.1 mg/kg butorphanol or equal volume (0.01 mL/kg) saline SQ in the cervical region. Thermal (TT) and pain pressure (PPT) thresholds at different body locations, along with physiological and behavioral variables, were assessed at baseline and up to 480 min post-injection. Data were analyzed using Stata/BE 17.0 and summarized as mean ± SD or median [interquartile range (IQR)], as appropriate. Mixed-effects linear regression (horse random effect) assessed treatment, time, and interaction effects ( ≤ 0.05). Adjusted marginal means (95% CI) were derived post-estimation. Unassigned: Butorphanol produced mild, transient sedation (Wald = 145.5, < 0.01) with a significant treatment × time interaction (LR = 46, < 0.01), peaking at 45-90 min after injection. Heart rate decreased over time with both treatments, and respiratory rate was briefly reduced at 10 min with butorphanol. Mean arterial pressure was unchanged overall, and no hypotension occurred. TT and thermal excursion (TE%) showed significant treatment × time interactions (TT: LR = 18.1, = 0.02; TE%: LR = 18.4, = 0.02) at the coronary band only, decreasing 60-240 min post-butorphanol injection. PPT showed no treatment × time interaction at any site. Unassigned: No clinically relevant treatment effect on TT or TE% was detected. Pressure pain threshold increased modestly for 1-2 h, but it was not statistically significant, likely due to variability and limited power. Subcutaneous butorphanol at 0.1 mg/kg produced mild, transient sedation with clinically acceptable cardiopulmonary effects, but without consistent antinociception.
Copyright © 2026 Masters, De Gennaro, Messer, Khatib, Moura, Mallicote and Chiavaccini.
Publication Date: 2026-10-09 PubMed ID: 42920775PubMed Central: PMC13691309DOI: 10.3389/fvets.2026.1970768Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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Overview
- This study investigated the pain-relieving (antinociceptive) effects of subcutaneous butorphanol in healthy horses, finding that while it caused mild, temporary sedation and was safe for heart and lung function, it did not provide consistent or clinically significant pain relief.
Background and Purpose
- Butorphanol is an opioid medication commonly used for pain relief in horses.
- Intravenous (IV) butorphanol clears from the bloodstream quickly, often requiring repeated dosing and increasing risk of adverse effects.
- Subcutaneous (SQ) administration maintains effective drug levels longer and tends to cause fewer side effects.
- The study aimed to assess if SQ butorphanol at 0.1 mg/kg produces meaningful antinociception—reduced pain sensitivity—in healthy horses.
Study Design
- Type: Blinded, randomized, crossover study ensuring each horse received both treatments (butorphanol and saline) at different times.
- Subjects: Eight healthy horses.
- Treatments:
- Butorphanol administered subcutaneously at 0.1 mg/kg in cervical (neck) region.
- Control treatment of equal volume saline injection (0.01 mL/kg) given subcutaneously.
- Measurements taken at baseline before injection and multiple time points up to 480 minutes (8 hours) after injection.
Parameters Measured
- Thermal Threshold (TT): The temperature at which horses showed a pain response when heat was applied.
- Thermal Excursion (TE%): The percent change in thermal threshold, indicating sensitivity to heat over time.
- Pain Pressure Threshold (PPT): The force applied at various body sites to elicit a pain response using pressure.
- Physiological variables: Heart rate, respiratory rate, mean arterial pressure to monitor cardiorespiratory safety.
- Behavioral assessment: Sedation severity and overall behavioral changes.
Key Findings
- Sedation: Butorphanol caused mild and temporary sedation noticeable between 45 and 90 minutes post-injection.
- Cardiopulmonary effects:
- Heart rate decreased over time similarly in both butorphanol and saline groups.
- Respiratory rate briefly decreased at 10 minutes after butorphanol injection, but changes were short-lived.
- No significant changes in mean arterial pressure; no episodes of hypotension were observed, indicating cardiovascular safety.
- Pain measurements:
- Thermal threshold and thermal excursion showed statistically significant treatment-by-time effects, but only at the coronary band (a distal body site) with a slight decrease in sensitivity 60–240 minutes after butorphanol.
- Pain pressure threshold did not show statistically significant changes after butorphanol at any site, though a modest increase was observed for 1–2 hours.
- Interpretation of results:
- The thermal sensitivity changes were not large enough to be considered clinically relevant.
- The increase in pressure pain threshold was mild and did not reach statistical significance, likely due to individual variability and the small sample size limiting study power.
- Overall, subcutaneous butorphanol did not provide consistent or robust pain relief in healthy horses.
Conclusions
- Subcutaneous administration of butorphanol at 0.1 mg/kg is safe for healthy horses, causing only mild and short-lived sedation without adverse cardiopulmonary effects.
- However, this dosing and route do not reliably produce meaningful antinociceptive effects as measured by thermal and pressure pain thresholds.
- Clinicians should be cautious about expecting significant pain relief from this butorphanol protocol and consider alternative or adjunctive analgesic strategies for managing pain in horses.
Cite This Article
APA
Masters TM, De Gennaro C, Messer SL, Khatib JL, Moura RA, Mallicote MF, Chiavaccini L.
(2026).
Antinociceptive effects of subcutaneous butorphanol administration in healthy horses.
Front Vet Sci, 13, 1970768.
https://doi.org/10.3389/fvets.2026.1970768 Publication
Researcher Affiliations
- Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
- Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
- Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
- Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
- Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
Conflict of Interest Statement
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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