VetMed

Birds: does butorphanol versus no analgesia reduce pain responses in validated models and clinical procedures? — POSSIBLE

In birds, does butorphanol vs no analgesia reduce pain responses in validated models and clinical procedures?

Shelf #959 · gate-verified and displayed under the developer's blinded-trial rule

POSSIBLE: Butorphanol raised pain thresholds versus saline in parrots and improved a functional pain outcome in lame chickens, but the effect was brief where its duration was measured, absent in kestrels, and no carded record tests a clinical surgical procedure. In African grey parrots randomly assigned to saline, butorphanol 1.0 mg/kg intramuscular or buprenorphine (Paul-Murphy 1999, 29 parrots), butorphanol significantly increased the withdrawal threshold to a noxious electrical stimulus while saline and buprenorphine did not — but an analgesic response occurred in only half the birds tested, and the abstract reports no threshold values. In orange-winged Amazon parrots (Laniesse 2020, 13 parrots, randomized crossover), intramuscular butorphanol 5 mg/kg significantly increased thermal threshold versus saline at 30 minutes, an effect the authors describe as small and lasting between 30 minutes and 1.5 hours; the sustained-release gel formulation showed no antinociceptive effect versus its controls. In a double-blind, randomized, controlled study in broiler chickens (Singh 2017), intravenous butorphanol 2 mg/kg was followed by lame chickens completing an obstacle course faster (36 ± 8 versus 69 ± 18 seconds), and the authors conclude it may be analgesic for up to 2 hours. Against this, in American kestrels (Guzman 2014, 15 birds, crossover, publication type Randomized Controlled Trial), butorphanol 1, 3 and 6 mg/kg intramuscular did not significantly increase thermal withdrawal thresholds versus saline in either sex, and the authors conclude it did not cause thermal antinociception suggestive of analgesia in kestrels. A liposome-encapsulated formulation in Hispaniolan parrots (Sladky 2006, 11 parrots) prolonged measurable analgesia to 3–5 days, a formulation effect, not plain butorphanol. Design class (a): Singh 2017 is randomised and double-blind by its own wording and answers this shelf's own comparison (butorphanol versus saline placebo) in birds, and Laniesse 2020 is a randomized crossover against saline. The stamp is POSSIBLE, not higher, because results conflict across species (positive in two parrot species and chickens, null in kestrels), samples are small (11–29 birds per record, with the chicken studies larger), effects are short-lived, responder rates are incomplete, and — stated as a gap, not a negative — no carded record measures pain after a clinical procedure or surgery in birds; all carded outcomes are stimulus thresholds or, in chickens, gait/obstacle performance in spontaneous lameness. One-home note: Shelf #325 (xylazine + butorphanol sedation in cattle, PMIDs 15136990, 41328727, 1429272) is a different species and question; none of its PMIDs is re-carded here. Drafted Nov 10, 2026 (VetMed build, topic #959); all figures from the abstract fetched and verified at drafting.

Singh 2017: in a double-blind randomized study, intravenous butorphanol 2 mg/kg was followed by lame broiler chickens completing an obstacle course in 36 ± 8 versus 69 ± 18 seconds

Double blind, randomized, controlled experimental study (record's own wording; publication type: Randomized Controlled Trial) — butorphanol versus saline placebo in lame and sound chickens

Who: Birds: broiler chickens with spontaneous lameness and sound controls, in a double blind, randomized, controlled experimental study. Study 1 used 36 lame and 36 sound chickens; study 2 used 48 lame and 48 sound chickens. Sound and lame chickens were gait scored and randomly assigned to sound-drug, sound-placebo, lame-drug and lame-placebo groups (study 2 added lame and sound handling control groups). Drug groups received morphine or butorphanol 2 mg/kg intravenously; placebo groups received an equal volume of normal saline. All birds underwent an obstacle course and a latency-to-lie test before injection and at 30 minutes and 2 hours after injection.

Result: Lame chickens finished the obstacle course faster (mean ± standard deviation 36 ± 8 compared with 69 ± 18 seconds) after the injection of butorphanol. In the lame handling control and placebo groups, obstacle course times increased and latency-to-lie times decreased with each observation. Morphine caused sedation with an increase in time taken to finish the obstacle course, even in sound chickens. The authors conclude intravenous butorphanol (2 mg/kg) may be analgesic in chickens for up to 2 hours, and that morphine caused sedation.

Watch out: The abstract does not state explicitly whether the 69 ± 18 second figure is the lame-butorphanol group's pre-injection time or the lame-placebo group's time, so this pack quotes the record's own comparison wording ('faster ... after the injection of butorphanol') rather than assigning it to a specific arm; the placebo and handling-control pattern (times worsening with each observation) is reported separately. The outcome is functional performance in spontaneously lame chickens, not a stimulus threshold and not postoperative pain; group sizes per arm are not stated. Morphine was a second drug arm in the same study — only its sedation finding is summarised here, as morphine is not this shelf's question.

Singh PM, Johnson CB, Gartrell B, Mitchinson S, Jacob A, Chambers P. Analgesic effects of morphine and butorphanol in broiler chickens. Vet Anaesth Analg. 2017;44(3):538-545. PMID: 28318988. Registry ID: none in the record. MeSH: Analgesia/methods, veterinary* · Analgesics, Opioid* · Animals · Butorphanol* · Chickens · Double-Blind Method · Lameness, Animal/drug therapy*, physiopathology · Morphine* · Poultry Diseases/drug therapy*, physiopathology

Paul-Murphy 1999: butorphanol 1.0 mg/kg significantly increased electrical-stimulus withdrawal threshold in African grey parrots while saline did not — but only half the birds responded

Randomly assigned experimental analgesia study (record's wording: birds 'were randomly assigned'; publication type: Journal Article, Research Support, Non-U.S. Gov't; blinding not stated)

Who: Birds: 29 African grey parrots (Psittacus erithacus erithacus and Psittacus erithacus timneh), conscious, in an experimental analgesia-evaluation setting. Each bird was fitted with an electrode on the medial metatarsal region of the right leg and an electrical stimulus (range 0.0 to 1.46 mA) was delivered through an aluminum perch; a withdrawal response was recorded when the bird lifted its foot or vigorously flinched its wings. After baseline threshold determination, birds were randomly assigned to receive an intramuscular injection of saline (0.9% NaCl) solution, butorphanol 1.0 mg/kg, or buprenorphine 0.1 mg/kg, and thresholds were determined again. Group sizes are not stated in the abstract.

Result: Butorphanol significantly increased threshold value, but saline solution or buprenorphine did not significantly change threshold values. The authors conclude butorphanol had an analgesic effect, significantly increasing the threshold to electrical stimuli in African grey parrots, that buprenorphine at the dosage used did not change the threshold, and that butorphanol provided an analgesic response in half of the birds tested and would be expected to provide analgesia in a clinical setting. No threshold values are reported in the abstract.

Watch out: Significance without numbers: the abstract gives no threshold values, effect size or P value, and the headline benefit applied to only half the birds tested — individual response was inconsistent. A single 1.0 mg/kg intramuscular dose and an electrical stimulus model in one parrot species; duration of effect is not reported in the abstract. The companion technique paper for this model (PMID: 10791932) was not carded, as it validates the measurement method rather than testing butorphanol's effect, and is cross-pointed here.

Paul-Murphy JR, Brunson DB, Miletic V. Analgesic effects of butorphanol and buprenorphine in conscious African grey parrots (Psittacus erithacus erithacus and Psittacus erithacus timneh). Am J Vet Res. 1999;60(10):1218-21. PMID: 10791933. Registry ID: none in the record. MeSH: Analgesia/methods, veterinary* · Animals · Bird Diseases/drug therapy · Buprenorphine/therapeutic use* · Butorphanol/therapeutic use* · Consciousness · Electric Stimulation · Pain/drug therapy, veterinary* · Pain Measurement/methods, veterinary · Pain Threshold · Parrots* · Species Specificity

Laniesse 2020: intramuscular butorphanol 5 mg/kg raised thermal threshold versus saline at 30 minutes in orange-winged Amazon parrots — a small effect lasting 30 minutes to 1.5 hours; the sustained-release gel showed no effect

Randomized complete crossover trials (record's own wording; publication type: Randomized Controlled Trial, Veterinary; blinding not stated)

Who: Birds: 13 orange-winged Amazon parrots (Amazona amazonica) in three randomized crossover trials. First, butorphanol tartrate 5 mg/kg or saline (0.9% NaCl) solution was administered intramuscularly in a randomized complete crossover design, with the thermal foot-withdrawal threshold determined 30 minutes before (baseline) and at various points after treatment. Second, butorphanol in a sustained-release 25% poloxamer 407 gel (But-P407, 12.5 mg/kg) or the gel vehicle (P407) was given subcutaneously in a similar crossover design. Third, But-P407 12.5 mg/kg or saline was given subcutaneously. Sedation was scored before each time point in all three trials.

Result: In the first trial, a significant increase in thermal threshold was noted 30 minutes after butorphanol tartrate (versus saline solution) administration, with no sedation noted. In the second and third trials, no significant difference was identified between But-P407 and either control treatment (saline solution or P407); mild sedation was noted in the second trial after But-P407. The authors conclude the results suggested a small but significant thermal antinociceptive effect of butorphanol tartrate lasting between 30 minutes and 1.5 hours in orange-winged Amazon parrots, that no antinociceptive effect was demonstrated when delivered in the gel, and that further research is needed on the gel. Threshold values are not reported in the abstract.

Watch out: Thirteen parrots and a surrogate thermal-threshold outcome; the plain-drug effect was significant at one reported time point (30 minutes) and is characterised by the authors themselves as small and brief (30 minutes to 1.5 hours). The title frames the study as subcutaneous administration, but the plain butorphanol arm was intramuscular and the subcutaneous arms were the gel formulation, which failed against both its controls — do not cite this record as support for subcutaneous or sustained-release butorphanol. No clinical pain or procedure outcome.

Laniesse D, Sanchez-Migallon Guzman D, Smith DA, Douglas JM, Mosley C, Beaufrère H, Paul-Murphy J. Evaluation of the thermal antinociceptive effects of subcutaneous administration of butorphanol tartrate or butorphanol tartrate in a sustained-release poloxamer 407 gel formulation to orange-winged Amazon parrots (Amazona amazonica). Am J Vet Res. 2020;81(7):543-550. PMID: 32584180. Registry ID: none in the record. MeSH: Amazona* · Analgesics, Opioid*/therapeutic use · Animals · Butorphanol*/therapeutic use · Cross-Over Studies · Delayed-Action Preparations · Parrots* · Poloxamer

Guzman 2014: butorphanol 1, 3 and 6 mg/kg did not significantly increase thermal withdrawal thresholds versus saline in American kestrels (the treatment made no difference)

Crossover experimental trial (publication type: Randomized Controlled Trial, Research Support, Non-U.S. Gov't; the abstract describes a crossover design and does not state blinding)

Who: Birds: 15 American kestrels (Falco sparverius), 2–3 years old (6 males, 9 females), in a crossover experimental design. Butorphanol (1, 3 and 6 mg/kg) and saline (0.9% NaCl) solution were administered intramuscularly. Agitation-sedation scores and foot withdrawal response to a thermal stimulus were determined 30–60 minutes before (baseline) and at 0.5, 1.5, 3 and 6 hours after treatment. For the pharmacokinetic analysis, butorphanol 6 mg/kg was administered intramuscularly into the pectoral muscles of 12 birds.

Result: In male kestrels, butorphanol did not significantly increase thermal thresholds for foot withdrawal compared with saline administration; at 1.5 hours after 6 mg/kg the thermal threshold was significantly decreased compared with baseline. In female kestrels, withdrawal threshold after butorphanol did not differ significantly from that after saline; compared with baseline, threshold was significantly increased for 1 mg/kg at 0.5 and 6 hours, 3 mg/kg at 6 hours, and 6 mg/kg at 3 hours. There were no significant differences in mean sedation-agitation scores except for males at 1.5 hours after 6 mg/kg. The authors conclude butorphanol did not cause thermal antinociception suggestive of analgesia in American kestrels, and that sex-dependent responses were identified.

Watch out: A genuine null against the saline comparator across three doses in a raptor species — the within-bird baseline comparisons that reached significance (scattered time points in females) did not survive comparison with saline, and one male time point went the wrong way (threshold significantly decreased at 1.5 hours after 6 mg/kg versus baseline). This record is why the pack cannot generalise the parrot findings to 'birds': analgesic response to butorphanol appears species-dependent. Thermal stimulus model only; no clinical procedure.

Guzman DS, Drazenovich TL, KuKanich B, Olsen GH, Willits NH, Paul-Murphy JR. Evaluation of thermal antinociceptive effects and pharmacokinetics after intramuscular administration of butorphanol tartrate to American kestrels (Falco sparverius). Am J Vet Res. 2014;75(1):11-8. PMID: 24370240. Registry ID: none in the record. MeSH: Analgesics, Opioid/administration & dosage*, pharmacokinetics*, therapeutic use · Animals · Butorphanol/administration & dosage*, pharmacokinetics*, therapeutic use · Procedural Sedation/methods, veterinary · Cross-Over Studies · Dose-Response Relationship, Drug · Female · Hot Temperature/adverse effects · Hypnotics and Sedatives/administration & dosage, pharmacokinetics, therapeutic use · Injections, Intramuscular/veterinary · Male · Nociceptive Pain/drug therapy, physiopathology, veterinary* · Pain Measurement/methods, veterinary · Raptors/physiology* · Sex Characteristics

Sladky 2006: liposome-encapsulated butorphanol gave analgesia lasting 3–5 days in Hispaniolan parrots, while standard intramuscular butorphanol was negligible in serum by 24 hours

Crossover pharmacokinetic and analgesic-efficacy study (publication type: Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Who: Birds: 11 adult Hispaniolan parrots (Amazona ventralis). Blood samples were collected at serial time points after subcutaneous liposome-encapsulated butorphanol tartrate (LEBT, 10 or 15 mg/kg) or intramuscular standard butorphanol tartrate (STDBT, 5 mg/kg), with serum concentrations measured by an immunoassay detecting parent drug and metabolites. Analgesic efficacy was evaluated using foot withdrawal thresholds to noxious thermal and electrical stimuli at baseline and serial time points after LEBT 15 mg/kg, liposome vehicle, STDBT 2 mg/kg, or physiologic saline (0.9% NaCl) solution.

Result: LEBT had a prolonged in vivo release for up to 5 days. Negligible serum butorphanol and metabolite concentrations were obtained at 24 hours after intramuscular STDBT. Analgesic efficacy of LEBT, measured by foot withdrawal threshold to noxious thermal and electrical stimuli, persisted for 3 to 5 days following subcutaneous LEBT administration. The authors conclude subcutaneous LEBT provided analgesia and detectable serum concentrations in Hispaniolan parrots for up to 5 days, and that its use may allow substantial improvement in long-term pain relief without the stress of handling and multiple daily injections.

Watch out: This is a formulation record: the 3–5 day analgesia belongs to an experimental liposome-encapsulated preparation, not to standard butorphanol, and the abstract does not report the standard-formulation (STDBT 2 mg/kg) threshold results separately from the LEBT findings, so no plain-butorphanol effect size can be taken from it. Eleven parrots, stimulus thresholds only. A later poloxamer-gel sustained-release study in a related parrot species (Laniesse 2020, carded above) found no antinociceptive effect for its gel formulation, so prolonged-release success is formulation-specific, not a class property.

Sladky KK, Krugner-Higby L, Meek-Walker E, Heath TD, Paul-Murphy J. Serum concentrations and analgesic effects of liposome-encapsulated and standard butorphanol tartrate in parrots. Am J Vet Res. 2006;67(5):775-81. PMID: 16649909. Registry ID: none in the record. MeSH: Amazona/blood* · Analgesia/veterinary* · Analgesics, Opioid/blood, pharmacokinetics, therapeutic use · Animals · Butorphanol/administration & dosage, blood*, pharmacokinetics, therapeutic use* · Chemistry, Pharmaceutical · Cross-Over Studies · Dose-Response Relationship, Drug · Liposomes/administration & dosage* · Pain/drug therapy*

Synthesis: butorphanol shows short-lived antinociception in parrots and a functional benefit in lame chickens, but no effect in kestrels and no clinical-procedure evidence in any bird species

Synthesis

Who: Synthesis of the cards above: Singh 2017 (double-blind randomized study, 72 chickens in study 1 and 96 in study 2, lame and sound), Paul-Murphy 1999 (29 African grey parrots, randomly assigned, electrical stimulus), Laniesse 2020 (13 orange-winged Amazon parrots, randomized crossover, thermal stimulus), Guzman 2014 (15 American kestrels, crossover, thermal stimulus) and Sladky 2006 (11 Hispaniolan parrots, crossover, liposome formulation).

Result: (1) Parrots, plain butorphanol versus saline: significant threshold increase in African greys at 1.0 mg/kg intramuscular, with a response in half the birds (Paul-Murphy); small significant thermal effect at 30 minutes, lasting 30 minutes to 1.5 hours, at 5 mg/kg intramuscular in orange-winged Amazons (Laniesse). (2) Chickens: lame birds completed an obstacle course faster after intravenous butorphanol 2 mg/kg (36 ± 8 versus 69 ± 18 seconds), authors' duration estimate up to 2 hours (Singh). (3) Kestrels: no significant threshold increase versus saline at 1, 3 or 6 mg/kg — a null (Guzman). (4) Formulations: liposome-encapsulated butorphanol prolonged analgesia to 3–5 days in Hispaniolan parrots (Sladky), while a poloxamer gel formulation showed no effect (Laniesse). (5) Clinical procedures: no carded record measures pain responses in a clinical procedure or after surgery in birds — that part of the question is unanswered, not answered negatively.

Watch out: Design class (a) rests on Singh 2017 (PMID: 28318988): randomised and double-blind by the record's own wording, answering this shelf's own comparison (butorphanol versus saline placebo) in birds; Laniesse 2020 adds a randomized crossover against saline. The class does not lift the stamp above POSSIBLE, because the blinded chicken result is a functional outcome in lameness, the parrot results are unblinded stimulus-threshold studies with incomplete responder rates, and a randomised crossover trial in kestrels was null — species cannot be pooled into a single 'birds' answer. Records deliberately not carded: intranasal butorphanol in broiler chickens (PMID: 35622740), a pharmacokinetic study (n = 6 per group) reporting nonsignificant nociceptive-threshold efficacy at 2 mg/kg intranasally, and butorphanol pharmacokinetic-only records (e.g. PMID: 26618732, 28541145) — cross-pointed here rather than carded, as they do not test analgesia against no analgesia. Boundary checked: Shelf #325 (cattle xylazine + butorphanol, PMIDs 15136990, 41328727, 1429272) shares no PMID with this pack.

Synthesis of Singh PM et al. PMID: 28318988; Paul-Murphy JR et al. PMID: 10791933; Laniesse D et al. PMID: 32584180; Guzman DS et al. PMID: 24370240; Sladky KK et al. PMID: 16649909. Registry IDs as on the individual cards.

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