Rabbits: does tramadol versus no opioid analgesia reduce pain responses after surgery? — POSSIBLE (the treatment made no difference)

In rabbits, does tramadol vs no opioid analgesia reduce pain responses after surgery?

Shelf #936 · gate-verified and displayed under the developer's blinded-trial rule

POSSIBLE (the treatment made no difference): In the one randomised, blinded clinical trial that tests this shelf's own comparison, adding tramadol to an anaesthetic protocol did not reduce postoperative pain in rabbits. Surita 2026 randomised 39 rabbits undergoing elective ovariohysterectomy to dexmedetomidine premedication alone (opioid-free control), dexmedetomidine + morphine 2 mg/kg, or dexmedetomidine + tramadol 10 mg/kg, with intravenous meloxicam 0.6 mg/kg in all arms: rescue analgesia was required by 7 of 13 tramadol rabbits (53.8%) and exactly 7 of 13 control rabbits (53.8%), versus 12 of 13 morphine rabbits (92.3%), and no tramadol-versus-control difference in Rabbit Pain Behaviour Scale scores was reported (the reported postoperative differences all involved the morphine group); the authors conclude none of the protocols provided adequate postoperative pain control. Design class (a): randomisation and blinding are established by the pivotal record's own title and design wording ('prospective, randomized, blinded clinical study'), and it answers the shelf's own comparison and population. Two smaller records point the same way for systemic tramadol but do not test this comparison directly: Oguntoye 2018 (6 rabbits) found neither midazolam–ketamine nor midazolam–ketamine + tramadol 4 mg/kg intramuscular produced analgesia. Epidural tramadol is a different question: Salem 2022 (24 male New Zealand White rabbits, experimental knee surgery) found epidural tramadol 4 mg/kg gave a duration of analgesia of 31.5 ± 2.3 minutes versus 23.3 ± 1.1 minutes for epidural lidocaine, and 45.8 ± 3.3 minutes for the combination — but every rabbit also received systemic butorphanol, there was no no-opioid control, and the route was epidural, so it cannot carry the systemic postoperative claim. Scope limits stated plainly: the pivotal trial tested a single premedication tramadol dose as an add-on to dexmedetomidine + meloxicam, in one operation (ovariohysterectomy) over 2–6 hours postoperatively; repeated dosing, other operations and tramadol as sole analgesia are unanswered, not answered negatively. One-home note: tramadol versus placebo for osteoarthritis pain in dogs homes on Shelf #510 with different PMIDs; no carded PMID here appears on that pack. Drafted Nov 10, 2026 (VetMed build, topic #936); all figures from the abstract fetched and verified at drafting.

Surita 2026: tramadol premedication made no difference after rabbit ovariohysterectomy — rescue analgesia in 7 of 13 tramadol rabbits (53.8%) and 7 of 13 opioid-free controls (53.8%), versus 12 of 13 (92.3%) on morphine

Prospective, randomized, blinded clinical study (record's own wording in its title; publication type: Journal Article)

Who: Rabbits: rabbits (Oryctolagus cuniculus) undergoing elective ovariohysterectomy in a clinical setting, in a prospective, randomized, blinded clinical study. Three premedication groups (n = 13 per group): CONTROL — dexmedetomidine 50 µg/kg (opioid-free); MOR — dexmedetomidine 50 µg/kg plus morphine 2 mg/kg; TRA — dexmedetomidine 50 µg/kg plus tramadol 10 mg/kg. All rabbits received intravenous meloxicam 0.6 mg/kg; anaesthesia was maintained with sevoflurane under mechanical ventilation, with a norepinephrine infusion started when arterial hypotension occurred. Postoperative pain and rescue analgesia were assessed with the Rabbit Pain Behaviour Scale from 2 to 6 hours after anaesthetic recovery (T2–T6); sedation was scored from 1 to 6 hours.

Result: Intraoperatively, CONTROL showed higher blood pressure and required less norepinephrine than MOR. Postoperatively, rescue analgesia was required in 12 MOR rabbits (92.3%) and in 7 TRA and 7 CONTROL rabbits (53.8% each) — identical rates for tramadol and opioid-free control. MOR had higher sedation scores, differing from the other groups at T2 and T4 and from CONTROL at T5 and T6, and higher pain scores, differing from the other groups at T2 and from CONTROL at T3; no tramadol-versus-control pain-score difference is reported. The authors conclude all protocols allowed completion of surgery without an exacerbated cardiovascular response, but none provided adequate postoperative pain control after ovariohysterectomy, as most rabbits required rescue analgesia, and that sedation appears to have influenced postoperative pain scoring, particularly in the MOR group.

Watch out: This is an add-on comparison: every rabbit received dexmedetomidine and meloxicam, so the trial tests whether tramadol adds analgesia on top of an NSAID-containing protocol, not tramadol versus nothing at all. A single premedication dose (10 mg/kg; route not stated in the abstract) and a short 2–6 hour postoperative window in one operation. Pain scores themselves are not numerically reported in the abstract — the checkable figures are the rescue-analgesia counts, which were identical (7/13 versus 7/13). The morphine arm's worse scores are attributed by the authors partly to sedation influencing scoring, a caution that applies to pain-scale interpretation generally.

Surita LE, Monteiro ER, Correia BS, Queiroga LB, Picoli R, Prado TW, Alievi MM. Effects of an opioid-free versus two opioid-based anesthetic protocols on intraoperative cardiovascular variables and postoperative pain in rabbits (Oryctolagus cuniculus) undergoing elective ovariohysterectomy: A prospective, randomized, blinded clinical study. Vet J. 2026;320:106942. PMID: 42962745. Registry ID: none in the record. MeSH: none in the record

Salem 2022: epidural tramadol gave 31.5 ± 2.3 minutes of analgesia versus 23.3 ± 1.1 minutes for epidural lidocaine in rabbits undergoing experimental knee surgery — a different route with no no-opioid control

Experimental epidural analgesia study in surgical rabbits (record's wording: rabbits 'allocated into three groups'; publication type: Journal Article; randomisation and blinding not stated)

Who: Rabbits: 24 male New Zealand White rabbits weighing 2.8–3.0 kg undergoing experimental knee surgery, allocated to three groups. All rabbits were anaesthetised with intramuscular ketamine 35 mg/kg, xylazine 5 mg/kg and butorphanol 0.1 mg/kg. Group A received lumbosacral epidural lidocaine 2% at 4 mg/kg; Group B received epidural tramadol 5% at 4 mg/kg; Group C received an epidural combination of lidocaine 4 mg/kg and tramadol 4 mg/kg. Recorded parameters included onset time of analgesia, duration of flaccid paralysis, duration of analgesia, onset and duration of sensory and motor blockade, heart rate, respiratory rate and rectal temperature.

Result: Duration of analgesia was 45.8 ± 3.3 minutes in the combination group (C), significantly increased (P < 0.05) versus lidocaine alone (23.3 ± 1.1 minutes, group A) and tramadol alone (31.5 ± 2.3 minutes, group B). Onset time of analgesia was significantly decreased in group C (46.5 ± 1.4 seconds) versus groups A and B (61.0 ± 2.4 and 54.5 ± 3.5 seconds). Duration of flaccid paralysis in group C (35.5 ± 2.9 minutes) is described in the record as significantly lower than in groups A and B (17.6 ± 1.4 and 21.8 ± 3.6 minutes) — the record's wording, although the printed value is numerically higher. Heart rate, respiratory rate and rectal temperature significantly decreased in group C compared with the other groups. The authors conclude epidural lidocaine combined with tramadol could be a better choice for potentiating analgesia than either drug separately in rabbits undergoing knee surgery.

Watch out: This card does NOT test this shelf's comparison: the route is epidural, the comparator is lidocaine (not no opioid analgesia), the outcomes are intraoperative blockade measures rather than postoperative pain, and every rabbit also received systemic butorphanol — an opioid — as part of general anaesthesia. It is carded to mark the boundary honestly: epidural tramadol showed measurable antinociception against lidocaine, which says nothing about systemic tramadol for postoperative pain. Note also the record's internal inconsistency on flaccid paralysis duration (a higher printed value described as 'significantly lower'), flagged rather than silently corrected. Group sizes per arm are not stated (24 rabbits, three groups).

Salem M, Rizk A, Mosbah E, Zaghloul A, Karrouf G, Abass M. Antinociceptive effect of lidocaine, tramadol, and their combination for lumbosacral epidural analgesia in rabbits undergoing experimental knee surgery. BMC Vet Res. 2022;18(1):252. PMID: 35768810. Registry ID: none in the record. MeSH: Animals · Male · Rabbits · Analgesia, Epidural*/veterinary · Analgesics · Lidocaine/pharmacology, therapeutic use · Pain/veterinary · Tramadol*/pharmacology, therapeutic use

Oguntoye 2018: neither midazolam–ketamine nor midazolam–ketamine + tramadol produced analgesia in 6 rabbits

Experimental anaesthesia evaluation (publication type: Journal Article; randomisation and blinding not stated)

Who: Rabbits: 6 healthy rabbits given intramuscular midazolam 2 mg/kg + ketamine 25 mg/kg alone (MK) and combined with tramadol 4 mg/kg (MKT), evaluated over a 60-minute observation period. Anaesthetic indices (time to loss of righting reflex, duration of recumbency, time to standing), heart rate, respiratory rate and rectal temperature were recorded, and analgesia was assessed. Whether the same 6 rabbits received both regimens is not stated in the abstract.

Result: Time to loss of righting reflex was significantly shorter with MKT (1.7 ± 0.3 minutes) than MK (4.2 ± 1.5 minutes) (P < 0.05). Duration of recumbency was similar (MKT 76.8 ± 5.1 minutes; MK 77.8 ± 3.6 minutes), and time to standing was shorter with MKT (9.3 ± 1.1 minutes) than MK (15.2 ± 2.4 minutes). Neither MK nor MKT produced analgesia. The authors conclude that although the inclusion of tramadol did not produce analgesia, it produced a faster onset of action than midazolam–ketamine alone, and that the combination would be useful for non-painful procedures where rapid drug action is needed.

Watch out: Six rabbits, no surgery and no postoperative pain outcome: this is an anaesthetic-protocol study whose analgesia assessment method is not described in the abstract, so 'neither produced analgesia' is a coarse, supportive signal only — it cannot substitute for the postoperative trial. The tramadol dose (4 mg/kg intramuscular, single) is lower than the pivotal trial's 10 mg/kg. MeSH on the record includes Xylazine/pharmacology although xylazine is not mentioned in the abstract's regimens.

Oguntoye CO, Oyewande OA, Afolabi OO. Evaluation of Tramadol-Midazolam-Ketamine Anaesthesia in Rabbits. Niger J Physiol Sci. 2018;33(2):145-149. PMID: 30837767. Registry ID: none in the record. MeSH: Anesthetics/pharmacology · Animals · Body Temperature/drug effects, physiology · Heart Rate/drug effects* · Ketamine/pharmacology* · Midazolam/pharmacology* · Pain/drug therapy · Rabbits · Tramadol/pharmacology* · Xylazine/pharmacology

Synthesis: systemic tramadol added nothing measurable after rabbit surgery in the one randomised blinded trial (the treatment made no difference); epidural tramadol data answer a different question

Synthesis

Who: Synthesis of the cards above: Surita 2026 (39 rabbits, randomised blinded clinical trial, tramadol or morphine premedication versus opioid-free control in ovariohysterectomy, all arms with meloxicam), Salem 2022 (24 male rabbits, epidural tramadol versus lidocaine in experimental knee surgery) and Oguntoye 2018 (6 rabbits, midazolam–ketamine with versus without tramadol, no surgery).

Result: (1) Postoperative pain after surgery, systemic tramadol versus no opioid: rescue analgesia 7/13 (53.8%) on tramadol versus 7/13 (53.8%) on opioid-free control; no tramadol–control pain-score difference reported; no protocol gave adequate control (Surita). (2) Anaesthetic-protocol antinociception: neither regimen with or without tramadol 4 mg/kg produced analgesia (Oguntoye). (3) Epidural route: tramadol 31.5 ± 2.3 minutes of analgesia versus lidocaine 23.3 ± 1.1 minutes, combination 45.8 ± 3.3 minutes — intraoperative blockade, not postoperative pain, with systemic butorphanol in all arms (Salem).

Watch out: Design class (a) rests on the pivotal record alone (Surita 2026, PMID: 42962745): randomised and blinded by its own wording, answering this shelf's own comparison in this shelf's own population. The null is a single-trial null at one dose, one operation and one short follow-up window, with an NSAID in every arm — it should not be read as proof that no tramadol regimen can help any rabbit after any surgery; repeated-dose and other-surgery questions remain unanswered. Boundary checked: Shelf #510 (tramadol versus placebo in canine osteoarthritis, PMIDs 29393744 and 23035739) is a different species and question, and none of its PMIDs is re-carded here.

Synthesis of Surita LE et al. PMID: 42962745; Salem M et al. PMID: 35768810; Oguntoye CO et al. PMID: 30837767. Registry IDs as on the individual cards.

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