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Abstract

Objective—To measure oxytocin concentrations in blood and CSF following central administration of opioid agonists in dogs.

Animals—5 male dogs.

Procedure—In a crossover design, CSF and blood were collected immediately before and 15 and 30 minutes after cisternal administration of D-Ala2, MePhe4, Gly-ol-enkephalin (DAMGO, a µ-receptor agonist); D-Pen, pCl-Phe4, D-Pen5-enkephalin (a δ-receptor agonist); U50488H (a κ-receptor agonist); morphine; and saline (0.9% NaCl) solution.

Results—Plasma oxytocin concentration was significantly increased 15 minutes after administration of DAMGO and 30 minutes after administration of U50488H, compared with concentrations obtained after administration of saline solution. Concentration of oxytocin in CSF was significantly decreased 30 minutes after administration of U50488H, compared with concentration after administration of saline solution.

Conclusion and Clinical Relevance—Results suggest that in male dogs, activation of centrally located µ and κ receptors elicits an overall excitatory effect on neurons that regulate peripheral release of oxytocin, whereas activation of centrally located κ receptors elicits an overall inhibitory effect on neurons that regulate central release. These results are in contrast to those reported for other species, in which opioids have a pronounced inhibitory effect on release of oxytocin from the neurohypophysis. (Am J Vet Res 2001; 62:496–499)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine frequency and severity of postanesthetic hypoxemia and hypercarbia in healthy dogs undergoing elective ovariohysterectomy or castration and given butorphanol or hydromorphone for analgesia.

Design—Prospective trial.

Animals—20 healthy dogs weighing > 10 kg (22 lb).

Procedure—Dogs were anesthestized with acepromazine, glycopyrrolate, thiopental, and isoflurane, and butorphanol (n = 10) or hydromorphone (10) was used for perioperative analgesia. Arterial blood gas analyses were performed 10 and 30 minutes and 1, 2, 3, and 4 hours after extubation.

Results—In dogs that received hydromorphone, mean PaCO2 was significantly higher, compared with the preoperative value, 10 and 30 minutes and 1, 2, and 3 hours after extubation. Mean PaCO2 was significantly higher in dogs given hydromorphone rather than butorphanol 10 and 30 minutes and 1 and 2 hours after extubation. Mean PaO2 was significantly lower, compared with preoperative values, 30 minutes and 1 and 2 hours after extubation in dogs given hydromorphone and 30 minutes after extubation in dogs given butorphanol. Mean PaO2 was significantly lower in dogs given hydromorphone rather than butorphanol 1 hour after extubation. Four dogs had PaO2 < 80 mm Hg 1 or more times after extubation.

Conclusions and Clinical Relevance—Results suggest that administration of hydromorphone to healthy dogs undergoing elective ovariohysterectomy or castration may result in transient increases in PaCO2 postoperatively and that administration of hydromorphone or butorphanol may result in transient decreases in PaO2. However, increases in PaCO2 and decreases in PaO2 were mild, and mean PaCO2 and PaO2 remained within reference limits. (J Am Vet Med Assoc 2003;222:330–336)

Full access
in Journal of the American Veterinary Medical Association

Objective—

To determine the association between subjective and objective variables commonly used to evaluate severity of postoperative pain in dogs. Design-Prospective double-blind study.

Animals—

36 dogs with unilateral rupture of the cranial cruciate ligament that underwent surgery to stabilize the stifle.

Procedure—

Each dog was assessed to determine severity of pain before and after surgery, using various subjective and objective criteria.

Results—

Subjective measures of pain (scores for visual analogue and numerical rating scales) correlated poorly or were not correlated with heart rate, respiratory rate, blood pressure, and results of a pain threshold test. Scores for visual analogue and numerical rating scales correlated with each other and with the amount of vocalization at most time periods.

Clinical Implications—

We detected a weak association between commonly employed subjective and objective measures of pain. This indicated that some of these measurement techniques do not predictably reflect severity of postoperative pain in dogs. Therefore, clinicians should not rely too heavily on these variables when assessing severity of postoperative pain in dogs. (J Am Vet Med Assoc 1997;210:1619–1622)

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in Journal of the American Veterinary Medical Association

SUMMARY

Naproxen (+6-methoxy- [α-methyl] -2-naphthalene acetic acid) is a nonsteroidal anti-inflammatory drug that is used for the treatment of inflammatory conditions in horses. We developed a model that describes the drug's disposition and renal excretion, including synovial fluid disposition and elimination after iv administration in horses. The plasma disposition, after iv administration of 5 mg/kg of body weight, was described by a two-compartment model; mean ± sd distribution and elimination half-lives were 1.42 ± 0.42 and 8.26 ± 2.56 hours, respectively. Plasma concentration of naproxen after iv administration of 5 mg/kg was 55.3 ± 13.5 and 0.61 ± 0.42 mg/L at 5 minutes and 48 hours after its administration, respectively. Steady-state volume of distribution was 0.163 ± 0.053 L/kg, and area under the plasma concentration time-curve was 372.1 ± 128.2 mg/h/L. The peak synovial fluid concentration of 12.68 ± 12.39 mg/L was measured at 6 hours, and decreased to 0.71 ± 0.38 mg/L at 36 hours after naproxen administration. The decrease of naproxen concentration in synovial fluid paralleled that in plasma. The appearance half-life of naproxen in synovial fluid was 4.64 hours, and the elimination half-life was 6.73 hours. Total body clearance was 0.015 ± 0.006 L/h/kg. The percentage of plasma protein binding was 97.0 ± 2.9% at plasma concentrations between 5 and 100 mg/L. This was significantly (P < 0.05) higher than the percentage of binding at plasma concentrations of 0.5, 1, and 500 mg/L, which was 75.2 ± 11.8%. Most of the drug was excreted as glucuronidated naproxen and unconjugated desmethylnaproxen. The recovery of naproxen and all metabolites in urine at 36 hours was 64.6 ± 7.2% of the total dose. Of this total, 39.6 ± 10.3% and 8.5 ± 7.9% were glucuronidated naproxen and desmethylnaproxen, respectively; 0.3 ± 0.1% and 16.6 ± 7.9% were free naproxen and desmethylnaproxen, respectively.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether changes in amplitude of the reflex-evoked muscle action potential (REMP) elicited by noninvasive dental dolorimetry (electrical stimulation of the tooth pulp) in anesthetized dogs may be used to objectively evaluate the effectiveness of IV and intrathecal (IT) administration of morphine.

Animals—6 male Beagles that were 2 to 6 years old.

Procedure—Dogs were used in a crossover design with at least a 5-day washout period between treatments. Each dog received morphine, saline (0.9% NaCl) solution, and oxytocin via the IV and IT routes of administration; however, only results for morphine and saline treatments were reported here. Dogs were anesthetized and prepared for noninvasive dental dolorimetry. After IV or IT administration, electrical stimulation was applied to a tooth, and REMPs of the digastricus muscle were recorded at 5-minute intervals for 60 minutes. To determine differences in REMP amplitude between treatments, a linear regression line was fitted for each dog-treatment combination.

Results—The IV administration of morphine significantly inhibited REMP amplitude, compared with IV administration of saline solution. Intrathecal administration of morphine significantly inhibited REMP amplitude, compared with IT administration of saline solution.

Conclusions and Clinical Relevance—Noninvasive dental dolorimetry in anesthetized dogs has promise as a technique for use in evaluating the analgesic potential of drugs administered IV and IT through evaluation of their effect on REMP amplitude recorded for the digastricus muscle. (Am J Vet Res 2002;63: 1349–1353)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether intrathecal (IT) or IV administration of oxytocin will diminish amplitude of the reflex-evoked muscle action potential (REMP) in the digastricus muscle during electrical stimulation of the tooth pulp in anesthetized dogs, thus suggesting an analgesic effect for oxytocin.

Animals—6 male Beagles that were 2 to 6 years old.

Procedure—Dogs were used in a crossover design with at least a 5-day washout period between treatments. Each dog received morphine, saline (0.9% NaCl) solution, and oxytocin by both the IT and IV routes of administration. Noninvasive dental dolorimetry was used to assess changes in pain threshold following administration of treatments. Effectiveness of analgesia was determined on the basis of change in REMP amplitude in the digastricus muscle.

Results—Morphine administered IV significantly inhibited REMP amplitude, compared with IV administration of saline solution or oxytocin. There was not a significant change in REMP amplitude between saline solution and oxytocin administered IV. Intrathecal administration of morphine significantly inhibited REMP amplitude, compared with IT administration of saline solution or oxytocin. Intrathecal administration of oxytocin significantly increased REMP amplitude, compared with IT administration of saline solution or morphine.

Conclusions and Clinical Relevance—Although IV administration of oxytocin did not have an effect on REMP amplitude, compared with IV administration of saline solution, IT administration of oxytocin had the opposite effect of morphine and increased REMP amplitude of the digastricus muscle. These data do not support the use of oxytocin as an analgesic agent in dogs. (Am J Vet Res 2002;63:1354–1358)

Full access
in American Journal of Veterinary Research