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- Author or Editor: Stephen M. Johnson x
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Abstract
Objective—To determine the effects of μ-, δ-, and κ-opioid receptor (MOR, DOR, and KOR, respectively) activation on thermal antinociception in red-eared slider turtles Trachemys scripta.
Animals—51 adult turtles.
Procedures—Infrared heat stimuli were applied to the plantar surface of turtle hind limbs. Thermal hind limb withdrawal latencies (HLWLs) were measured before (baseline) and at intervals after SC administration of various doses of saline (0.9% NaCl) solution (SS), MOR, DOR, or KOR agonists (3 to 13 turtles/treatment). Treatment with a DOR antagonist SC prior to DOR agonist administration was also evaluated.
Results—Treatment with an MOR agonist ([D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin acetate salt [DAMGO; 1.3 or 6.6 mg/kg]) increased HLWLs (from baseline) at 2 to 8 hours after injection; at the higher dose, the maximum mean increase was 5.6 seconds at 4 hours. Treatment with a DOR agonist ([D-Ala2, D-Leu5]-enkephalin acetate salt [DADLE; 25 mg/kg]) increased mean HLWL by 11.3 seconds at 4 hours; however, treatment with DADLE (5.8 mg/kg) or with another DOR agonist ([D-Pen2,5]-enkephalin hydrate [DPDPE; 1.2 or 6.3 mg/kg]) did not alter HLWL, compared with SS effects. Administration of a DOR antagonist (naltrindole hydrochloride; 10 mg/kg) prior to DADLE administration (25 mg/kg) increased mean HLWL by 2.7 seconds at 4 hours. One KOR agonist, U50488 ([−]-trans-[1S,2S]-U50488 hydrochloride hydrate; 6.7 mg/kg) decreased HLWL steadily from 2 to 24 hours (less than baseline value); another KOR agonist, U69593 ([+]-[5α,7α,8β]-N-Methyl-N-[7-{1-pyrrolidinyl}-1-oxaspiro{4.5}dec-8-yl]-benzene-acet-amide; 6.7 or 26 mg/kg) did not alter HLWLs, compared with SS effects.
Conclusions and Clinical Relevance—Opioid-dependent thermal antinociception in turtles appeared to be attributable mainly to MOR activation with a relatively minor contribution of DOR activation.
Abstract
OBJECTIVE
To determine the effects of dexmedetomidine, doxapram, and dexmedetomidine plus doxapram on ventilation (
e), breath frequency, and tidal volume (Vt) in ball pythons (Python regius) and of doxapram on the thermal antinociceptive efficacy of dexmedetomidine.
ANIMALS
14 ball pythons.
PROCEDURES
Respiratory effects of dexmedetomidine and doxapram were assessed with whole-body, closed-chamber plethysmography, which allowed for estimates of
e and Vt. In the first experiment of this study with a complete crossover design, snakes were injected, SC, with saline (0.9% NaCl) solution, dexmedetomidine (0.1 mg/kg), doxapram (10 mg/kg), or dexmedetomidine and doxapram, and breath frequency,
e, and Vt were measured before and every 30 minutes thereafter, through 240 minutes. In the second experiment, antinociceptive efficacy of saline solution, dexmedetomidine, and dexmedetomidine plus doxapram was assessed by measuring thermal withdrawal latencies before and 60 minutes after SC injection.
RESULTS
Dexmedetomidine significantly decreased breath frequency and increased Vt but did not affect
e at all time points, compared with baseline. Doxapram significantly increased
e, breath frequency, and Vt at 60 minutes after injection, compared with saline solution. The combination of dexmedetomidine and doxapram, compared with dexmedetomidine alone, significantly increased
e at 30 and 60 minutes after injection and did not affect breath frequency and Vt at all time points. Thermal withdrawal latencies significantly increased when snakes received dexmedetomidine or dexmedetomidine plus doxapram, versus saline solution.
CONCLUSIONS AND CLINICAL RELEVANCE
Concurrent administration of doxapram may mitigate the dexmedetomidine-induced reduction of breathing frequency without disrupting thermal antinociceptive efficacy in ball pythons.
Abstract
Objective—To determine the dose- and time-dependent changes in analgesia and respiration caused by tramadol administration in red-eared slider turtles (Trachemys scripta).
Design—Crossover study.
Animals—30 adult male and female red-eared slider turtles.
Procedures—11 turtles received tramadol at various doses (1, 5, 10, or 25 mg/kg [0.45, 2.27, 4.54, or 11.36 mg/lb], PO; 10 or 25 mg/kg, SC) or a control treatment administered similarly. Degree of analgesia was assessed through measurement of hind limb thermal withdrawal latencies (TWDLs) at 0, 3, 6, 12, 24, 48, 72, and 96 hours after tramadol administration. Nineteen other freely swimming turtles received tramadol PO (5, 10, or 25 mg/kg), and ventilation (VE), breath frequency, tidal volume (VT), and expiratory breath duration were measured.
Results—The highest tramadol doses (10 and 25 mg/kg, PO) yielded greater mean TWDLs 6 to 96 hours after administration than the control treatment did, whereas tramadol administered at 5 mg/kg, PO, yielded greater mean TWDLs at 12 and 24 hours. The lowest tramadol dose (1 mg/kg, PO) failed to result in analgesia. Tramadol administered SC resulted in lower TWDLs, slower onset, and shorter duration of action, compared with PO administration. Tramadol at 10 and 25 mg/kg, PO, reduced the VE at 12 hours by 51% and 67%, respectively, and at 24 through 72 hours by 55% to 62% and 61 % to 70%, respectively. However, tramadol at 5 mg/kg, PO, had no effect on the VE.
Conclusions and Clinical Relevance—Tramadol administered PO at 5 to 10 mg/kg provided thermal analgesia with less respiratory depression than that reported for morphine in red-eared slider turtles.
Abstract
OBJECTIVE To determine antinociceptive efficacy, behavioral patterns, and respiratory effects associated with dexmedetomidine administration in ball pythons (Python regius).
ANIMALS 12 ball pythons.
PROCEDURES Antinociception was assessed by applying an infrared heat stimulus to the cranioventral surface of snakes during 2 experiments. Thermal withdrawal latency was measured at 0, 2, and 24 hours after SC injections of dexmedetomidine (0.1 or 0.2 mg/kg) or saline (0.9% NaCl) solution and at 0 to 60 minutes after injection of dexmedetomidine (0.1 mg/kg) or saline solution. Behaviors were recorded at 0, 2, and 24 hours after administration of dexmedetomidine (0.1 mg/kg) or saline solution. Tongue flicking, head flinch to the approach of an observer's hand, movement, and righting reflex were scored. Respiratory frequency was measured by use of plethysmography to detect breathing-related movements after injection of dexmedetomidine (0.1 mg/kg) or saline solution.
RESULTS Mean baseline withdrawal latency was 5 to 7 seconds; saline solution did not alter withdrawal latency. Dexmedetomidine increased withdrawal latency by 18 seconds (0.2 mg/kg) and 13 seconds (0.1 mg/kg) above baseline values at 2 hours. Increased withdrawal latency was detected within 15 minutes after dexmedetomidine administration. At 2 hours after injection, there were few differences in behavioral scores. Dexmedetomidine injection depressed respiratory frequency by 55% to 70%, compared with results for saline solution, but snakes continued to breathe without prolonged apnea.
CONCLUSIONS AND CLINICAL RELEVANCE Dexmedetomidine increased noxious thermal withdrawal latency without causing excessive sedation. Therefore, dexmedetomidine may be a useful analgesic drug in ball pythons and other snake species.
Abstract
Objective—To test the hypothesis that administration of butorphanol or morphine induces antinociception in bearded dragons and corn snakes.
Design—Prospective crossover study.
Animals—12 juvenile and adult bearded dragons and 13 corn snakes.
Procedures—Infrared heat stimuli were applied to the plantar surface of bearded dragon hind limbs or the ventral surface of corn snake tails. Thermal withdrawal latencies (TWDLs) were measured before (baseline) and after SC administration of physiologic saline (0.9% NaCl) solution (equivalent volume to opioid volumes), butorphanol tartrate (2 or 20 mg/kg [0.91 or 9.1 mg/lb]), or morphine sulfate (1, 5, 10, 20, or 40 mg/kg [0.45, 2.27, 4.5, 9.1, or 18.2 mg/lb]).
Results—For bearded dragons, butorphanol (2 or 20 mg/kg) did not alter hind limb TWDLs at 2 to 24 hours after administration. However, at 8 hours after administration, morphine (10 and 20 mg/kg) significantly increased hind limb TWDLs from baseline values (mean ± SEM maximum increase, 2.7 ± 0.4 seconds and 2.8 ± 0.9 seconds, respectively). For corn snakes, butorphanol (20 mg/kg) significantly increased tail TWDLs at 8 hours after administration (maximum increase from baseline value, 3.0 ± 0.8 seconds); the low dose had no effect. Morphine injections did not increase tail TWDLs at 2 to 24 hours after administration.
Conclusions and Clinical Relevance—Compared with doses used in most mammalian species, high doses of morphine (but not butorphanol) induced analgesia in bearded dragons, whereas high doses of butorphanol (but not morphine) induced analgesia in corn snakes.
Abstract
Objective—To identify pain-related behaviors and assess the effects of butorphanol tartrate and morphine sulfate in koi (Cyprinus carpio) undergoing unilateral gonadectomy.
Design—Prospective study.
Animals—90 adult male and female koi.
Procedures—Each fish received saline (0.9% NaCl) solution (which is physiologically compatible with fish) IM, butorphanol (10 mg/kg [4.5 mg/lb], IM), or morphine (5 mg/kg [2.3 mg/lb], IM) as an injection only (6 fish/treatment); an injection with anesthesia and surgery (12 fish/treatment); or an injection with anesthesia but without surgery (12 fish/treatment). Physiologic and behavioral data were recorded 12 hours before and at intervals after treatment.
Results—Compared with baseline values, the saline solution–surgery group had significantly decreased respiratory rates (at 12 to 24 hours), food consumption assessed as a percentage of floating pellets consumed (at 0 to 36 hours), and activity score (at 0 to 48 hours). Respiratory rate decreased in all butorphanol-treated fish; significant decreases were detected at fewer time points following morphine administration. In the butorphanol-surgery group, the value for food consumption initially decreased but returned to baseline values within 3 hours after treatment; food consumption did not change in the morphine-surgery group. Surgery resulted in decreased activity, regardless of treatment, with the most pronounced effect in the saline solution–surgery group. Changes in location in water column, interactive behavior, and hiding behavior were not significantly different among groups. Butorphanol and morphine administration was associated with temporary buoyancy problems and temporary bouts of excessive activity, respectively.
Conclusions and Clinical Relevance—Butorphanol and morphine appeared to have an analgesic effect in koi, but morphine administration caused fewer deleterious adverse effects. Food consumption appeared to be a reliable indicator of pain in koi.
Abstract
Objective—To determine cytologic and microbiologic findings in bronchoalveolar lavage (BAL) fluid and SpO 2 values obtained during BAL in healthy rabbits.
Animals—9 rabbits.
Procedures—Bronchoscopic BAL of left and right caudal lobar bronchi (LB2 and RB4) was performed with 3 mL of sterile saline (0.9% NaCl) solution; SpO 2 was measured before, during, and after BAL. Percentage fluid recovered, total leukocyte counts, and differential cell counts were determined. Aerobic and anaerobic bacterial, mycoplasmal, and fungal cultures were performed from combined LB2 and RB4 samples.
Results—Mean ± SD percentage fluid volumes recovered from LB2 and RB4 were 53 ± 13% and 63 ± 13%, respectively. Mean ± SD total leukocyte counts from LB2 and RB4 were 422 ± 199 cells/μL and 378 ± 97 cells/μL, respectively. Macrophages were most frequently identified. There were no significant differences in volumes retrieved, total leukocyte counts, or differential cell percentages between LB2 and RB4. Microbial culture results were negative for 3 rabbits and positive for mixed aerobic and anaerobic bacterial growth in 6 and 2 rabbits, respectively. The SpO 2 was ≥ 95% in 7 of 9 rabbits after anesthetic induction, < 95% in 5 of 6 rabbits 1 minute after BAL, and ≥ 95% in 5 of 9 rabbits and > 90% in 4 of 9 rabbits 3 minutes after BAL.
Conclusions and Clinical Relevance—Bronchoscopic BAL with 3 mL of saline solution provided adequate fluid recovery for microbiologic and cytologic examination from the caudal lung lobes. Transient low SpO 2 was detected immediately after BAL.
Abstract
Objective—To test the hypothesis that butorphanol or morphine induces antinociception with minimal respiratory depression in conscious red-eared slider turtles.
Design—Prospective crossover study.
Animals—37 adult male and female red-eared slider turtles (Trachemys scripta).
Procedures—Antinociception (n = 27 turtles) and respiratory (10 turtles) experiments were performed. Infrared heat stimuli were applied to the plantar surface of turtle limbs. Thermal withdrawal latencies were measured before and at intervals after SC administration of physiologic saline (0.9% NaCl) solution, butorphanol tartrate (2.8 or 28 mg/kg [1.27 or 12.7 mg/lb]), or morphine sulfate (1.5 or 6.5 mg/kg [0.68 or 2.95 mg/lb]). Ventilation was assessed in freely swimming turtles before and after SC administration of saline solution, butorphanol (28 mg/kg), or morphine (1.5 mg/kg).
Results—For as long as 24 hours after injection of saline solution or either dose of butorphanol, thermal withdrawal latencies among turtles did not differ. Low- and high-dose morphine injections increased latencies significantly by 8 hours. Ventilation was not altered by saline solution administration, was temporarily depressed by 56% to 60% for 1 to 2 hours by butorphanol (28 mg/kg) administration, and was significantly depressed by a maximum of 83 ± 9% at 3 hours after morphine (1.5 mg/kg) injection. Butorphanol and morphine depressed ventilation by decreasing breathing frequency.
Conclusions and Clinical Relevance—Although widely used in reptile species, butorphanol may not provide adequate antinociception for invasive procedures and caused short-term respiratory depression in red-eared slider turtles. In contrast, morphine apparently provided antinociception but caused long-lasting respiratory depression.
Abstract
OBJECTIVE To quantify plasma fentanyl concentrations (PFCs) and evaluate antinociceptive and respiratory effects following application of transdermal fentanyl patches (TFPs) and assess cerebrospinal μ-opioid receptor mRNA expression in ball pythons (compared with findings in turtles).
ANIMALS 44 ball pythons (Python regius) and 10 turtles (Trachemys scripta elegans).
PROCEDURES To administer 3 or 12 μg of fentanyl/h, a quarter or whole TFP (TFP-3 and TFP-12, respectively) was used. At intervals after TFP-12 application in snakes, PFCs were measured by reverse-phase high-pressure liquid chromatography. Infrared heat stimuli were applied to the rostroventral surface of snakes to determine thermal withdrawal latencies after treatments with no TFP (control [n = 16]) and TFP-3 (8) or TFP-12 (9). Breathing frequency was measured in unrestrained controls and TFP-12–treated snakes. μ-Opioid receptor mRNA expression in brain and spinal cord tissue samples from snakes and turtles (which are responsive to μ-opioid receptor agonist drugs) were quantified with a reverse transcription PCR assay.
RESULTS Mean PFCs were 79, 238, and 111 ng/mL at 6, 24, and 48 hours after TFP-12 application, respectively. At 3 to 48 hours after TFP-3 or TFP-12 application, thermal withdrawal latencies did not differ from pretreatment values or control treatment findings. For TFP-12–treated snakes, mean breathing frequency significantly decreased from the pretreatment value by 23% and 41% at the 24- and 48-hour time points, respectively. Brain and spinal cord tissue μ-opioid receptor mRNA expressions in snakes and turtles did not differ.
CONCLUSIONS AND CLINICAL RELEVANCE In ball pythons, TFP-12 application resulted in high PFCs, but there was no change in thermal antinociception, indicating resistance to μ-opioid-dependent antinociception in this species.
