Abstract
The provision of adequate analgesia after an invasive procedure or for general pain management is an important component of laboratory animal care. Choosing the appropriate analgesic requires careful consideration by the investigators, the veterinary team and the institution's ethical review committee. Sustained-delivery analgesics are superior to analgesics with short durations of action because they do not need to be administered multiple times, reducing handling-induced stress to the animal, and they provide sustained plasma concentrations of the analgesic over the treatment period. The author reviews analgesic formulations that have durations of action longer than 12 h and up to 72 h. These options should be considered when appropriate for particular procedures and animal species.
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References
Mohawk, J.A. & Lee, T.M. Restraint stress delays reentrainment in male and female diurnal and nocturnal rodents. J. Biol. Rhythms 20, 245–256 (2005).
Abelson, K.S., Jacobsen, K.R., Sundbom, R., Kalliokoski, O. & Hau, J. Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice. Lab. Anim. 46, 349–351 (2012).
Goldkuhl, R., Hau, J. & Abelson, K.S. Effects of voluntarily-ingested buprenorphine on plasma corticosterone levels, body weight, water intake, and behaviour in permanently catheterised rats. In Vivo 24, 131–135 (2010).
Liles, J.H., Flecknell, P.A., Roughan, J. & Cruz-Madorran, I. Influence of oral buprenorphine, oral naltrexone or morphine on the effects of laparotomy in the rat. Lab. Anim. 32, 149–161 (1998).
Heavner, J.E. & Cooper, D.M. in Anesthesia and Analgesia in Laboratory Animals, 2nd edn. (eds. Fish, R. E., Brown, M.J., Danneman, P.J. & Karas, A.Z.) 97–123 (Academic, London, UK, 2008).
Leach, M.C., Bailey, H.E., Dickinson, A.L., Roughan, J.V. & Flecknell, P.A. A preliminary investigation into the practicality of use and duration of action of slow-release preparations of morphine and hydromorphone in laboratory rats. Lab. Anim. 44, 59–65 (2010).
Cooper, D.M., DeLong, D. & Gillett, C.S. Analgesic efficacy of acetaminophen and buprenorphine administered in the drinking water of rats. Contemp. Top. Lab. Anim. Sci. 36, 58–62 (1997).
Hayes, K.E., Raucci, J.A. Jr., Gades, N.M. & Toth, L.A. An evaluation of analgesic regimens for abdominal surgery in mice. Contemp. Top. Lab. Anim. Sci. 39, 18–23 (2000).
Mickley, G.A., Hoxha, Z., Biada, J.M., Kenmuir, C.L. & Bacik, S.E. Acetaminophen self-administered in the drinking water increases the pain threshold of rats (Rattus norvegicus). J. Am. Assoc. Lab. Anim. Sci. 45, 48–54 (2006).
Arras, M., Rettich, A., Cinelli, P., Kasermann, H.P. & Burki, K. Assessment of post-laparotomy pain in laboratory mice by telemetric recording of heart rate and heart rate variability. BMC Vet. Res. 3, 16 (2007).
Stasiak, K.L., Maul, D., French, E., Hellyer, P.W. & VandeWoude, S. Species-specific assessment of pain in laboratory animals. Contemp. Top. Lab. Anim. Sci. 42, 13–20 (2003).
Johnson, R.F. & Johnson, A.K. Light/dark cycle modulates food to water intake ratios in rats. Physiol. Behav. 48, 707–711 (1990).
Puryear, R., Rigatto, K.V., Amico, J.A. & Morris, M. Enhanced salt intake in oxytocin deficient mice. Exp. Neurol. 171, 323–328 (2001).
Bachmanov, A.A., Reed, D.R., Beauchamp, G.K. & Tordoff, M.G. Food intake, water intake, and drinking spout side preference of 28 mouse strains. Behav. Genet. 32, 435–443 (2002).
Tordoff, M.G., Bachmanov, A.A. & Reed, D.R. Forty mouse strain survey of water and sodium intake. Physiol. Behav. 91, 620–631 (2007).
Cowan, A., Doxey, J.C. & Harry, E.J. The animal pharmacology of buprenorphine, an oripavine analgesic agent. Br. J. Pharmacol. 60, 547–554 (1977).
Hofmeister, E.H. & Egger, C.M. Transdermal fentanyl patches in small animals. J. Am. Anim. Hosp. Assoc. 40, 468–478 (2004).
Kurz, A. & Sessler, D.I. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs 63, 649–671 (2003).
Pairet, M. & Ruckebusch, Y. On the relevance of non-steroidal anti-inflammatory drugs in the prevention of paralytic ileus in rodents. J. Pharm. Pharmacol. 41, 757–761 (1989).
Jeal, W. & Benfield, P. Transdermal fentanyl. A review of its pharmacological properties and therapeutic efficacy in pain control. Drugs 53, 109–138 (1997).
Kyles, A.E., Papich, M. & Hardie, E.M. Disposition of transdermally administered fentanyl in dogs. Am. J. Vet. Res. 57, 715–719 (1996).
Kyles, A.E., Hardie, E.M., Hansen, B.D. & Papich, M.G. Comparison of transdermal fentanyl and intramuscular oxymorphone on post-operative behaviour after ovariohysterectomy in dogs. Res. Vet. Sci. 65, 245–251 (1998).
Egger, C.M., Glerum, L.E., Allen, S.W. & Haag, M. Plasma fentanyl concentrations in awake cats and cats undergoing anesthesia and ovariohysterectomy using transdermal administration. Vet. Anaesth. Analg. 30, 229–236 (2003).
Glerum, L.E., Egger, C.M., Allen, S.W. & Haag, M. Analgesic effect of the transdermal fentanyl patch during and after feline ovariohysterectomy. Vet. Surg. 30, 351–358 (2001).
Lee, D.D., Papich, M.G. & Hardie, E.M. Comparison of pharmacokinetics of fentanyl after intravenous and transdermal administration in cats. Am. J. Vet. Res. 61, 672–677 (2000).
Foley, P.L., Henderson, A.L., Bissonette, E.A., Wimer, G.R. & Feldman, S.H. Evaluation of fentanyl transdermal patches in rabbits: blood concentrations and physiologic response. Comp. Med. 51, 239–244 (2001).
Harvey-Clark, C.J., Gilespie, K. & Riggs, K.W. Transdermal fentanyl compared with parenteral buprenorphine in post-surgical pain in swine: a case study. Lab. Anim. 34, 386–398 (2000).
Malavasi, L.M., Augustsson, H., Jensen-Waern, M. & Nyman, G. The effect of transdermal delivery of fentanyl on activity in growing pigs. Acta Vet. Scand. 46, 149–157 (2005).
Malavasi, L.M., Nyman, G., Augustsson, H., Jacobson, M. & Jensen-Waern, M. Effects of epidural morphine and transdermal fentanyl analgesia on physiology and behaviour after abdominal surgery in pigs. Lab. Anim. 40, 16–27 (2006).
Wilkinson, A.C., Thomas, M.L. 3rd & Morse, B.C. Evaluation of a transdermal fentanyl system in yucatan miniature pigs. Contemp. Top. Lab. Anim. Sci. 40, 12–16 (2001).
Ahern, B.J., Soma, L.R., Boston, R.C. & Schaer, T.P. Comparison of the analgesic properties of transdermally administered fentanyl and intramuscularly administered buprenorphine during and following experimental orthopedic surgery in sheep. Am. J. Vet. Res. 70, 418–422 (2009).
Ahern, B.J., Soma, L.R., Rudy, J.A., Uboh, C.E. & Schaer, T.P. Pharmacokinetics of fentanyl administered transdermally and intravenously in sheep. Am. J. Vet. Res. 71, 1127–1132 (2010).
Nexcyon Pharmaceuticals Inc. Recuvyra Fentanyl Transdermal Solution Dogs: For the control of postoperative pain associated with surgical procedures in dogs. NADA 141-337. FDA http://www.fda.gov/downloads/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/FOIADrugSummaries/UCM314828.pdf (2012).
Freise, K.J., Linton, D.D., Newbound, G.C., Tudan, C. & Clark, T.P. Population pharmacokinetics of transdermal fentanyl solution following a single dose administered prior to soft tissue and orthopedic surgery in dogs. J. Vet. Pharmacol. Ther. 35 (suppl. 2), 65–72 (2012).
Freise, K.J., Newbound, G.C., Tudan, C. & Clark, T.P. Pharmacokinetics and the effect of application site on a novel, long-acting transdermal fentanyl solution in healthy laboratory Beagles. J. Vet. Pharmacol. Ther. 35 (suppl. 2), 27–33 (2012).
Freise, K.J. et al. Pharmacokinetics and dose selection of a novel, long-acting transdermal fentanyl solution in healthy laboratory Beagles. J. Vet. Pharmacol. Ther. 35 (suppl. 2), 21–26 (2012).
Linton, D.D., Wilson, M.G., Newbound, G.C., Freise, K.J. & Clark, T.P. The effectiveness of a long-acting transdermal fentanyl solution compared to buprenorphine for the control of postoperative pain in dogs in a randomized, multicentered clinical study. J. Vet. Pharmacol. Ther. 35, 53–64 (2012).
Savides, M.C. et al. The margin of safety of a single application of transdermal fentanyl solution when administered at multiples of the therapeutic dose to laboratory dogs. J. Vet. Pharmacol. Ther. 35 (suppl. 2), 35–43 (2012).
Roy, S.D. & Flynn, G.L. Transdermal delivery of narcotic analgesics: pH, anatomical, and subject influences on cutaneous permeability of fentanyl and sufentanil. Pharm. Res. 7, 842–847 (1990).
Deschamps, J.Y. et al. Fatal overdose after ingestion of a transdermal fentanyl patch in two non-human primates. Vet. Anaesth. Analg. 39, 653–656 (2012).
Freise, K.J., Newbound, G.C., Tudan, C. & Clark, T.P. Naloxone reversal of an overdose of a novel, long-acting transdermal fentanyl solution in laboratory Beagles. J. Vet. Pharmacol. Ther. 35 (suppl. 2), 45–51 (2012).
Cowan, A., Lewis, J.W. & Macfarlane, I.R. Agonist and antagonist properties of buprenorphine, a new antinociceptive agent. Br. J. Pharmacol. 60, 537–545 (1977).
Dahan, A. et al. Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats. Br. J. Anaesth. 94, 825–834 (2005).
Hans, G. & Robert, D. Transdermal buprenorphine—a critical appraisal of its role in pain management. J. Pain Res. 2, 117–134 (2009).
Murrell, J.C. et al. Use of a transdermal matrix patch of buprenorphine in cats: preliminary pharmacokinetic and pharmacodynamic data. Vet. Rec. 160, 578–583 (2007).
Boas, R.A. & Villiger, J.W. Clinical actions of fentanyl and buprenorphine. The significance of receptor binding. Br. J. Anaesth. 57, 192–196 (1985).
Moll, X., Fresno, L., García, F., Prandi, D. & Andaluz, A. Comparison of subcutaneous and transdermal administration of buprenorphine for pre-emptive analgesia in dogs undergoing elective ovariohysterectomy. Vet. J. 187, 124–128 (2011).
Pieper, K., Schuster, T., Levionnois, O., Matis, U. & Bergadano, A. Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs. Vet. J. 187, 335–341 (2011).
Andaluz, A. et al. Plasma buprenorphine concentrations after the application of a 70 microg/h transdermal patch in dogs. Preliminary report. J. Vet. Pharmacol. Ther. 32, 503–505 (2009).
Park, I. et al. Buprederm, a new transdermal delivery system of buprenorphine: pharmacokinetic, efficacy and skin irritancy studies. Pharm. Res. 25, 1052–1062 (2008).
Yun, M., Jeong, S., Pai, C. & Kim, S. Pharmacokinetic-pharmacodynamic modeling of the analgesic effect of bupredermTM, in mice. Health 2, 824–831 (2010).
Plosker, G.L. & Lyseng-Williamson, K.A. Buprenorphine 5, 10 and 20 μg/h transdermal patch: a guide to its use in chronic non-malignant pain. CNS Drugs 26, 367–373 (2012).
Mazières, B. Topical ketoprofen patch. Drugs R. D. 6, 337–344 (2005).
Bergese, S.D. et al. Efficacy profile of liposome bupivacaine, a novel formulation of bupivacaine for postsurgical analgesia. J. Pain Res. 5, 107–116 (2012).
Richard, B.M. et al. Safety evaluation of EXPAREL (DepoFoam Bupivacaine) administered by repeated subcutaneous injection in rabbits and dogs: species comparison. J. Drug Deliv. 2011, 467429 (2011).
Richard, B.M. et al. The safety of EXPAREL® (Bupivacaine Liposome Injectable Suspension) administered by peripheral nerve block in rabbits and dogs. J. Drug Deliv. 2012, 962101 (2012).
Krugner-Higby, L. et al. Liposome-encapsulated oxymorphone hydrochloride provides prolonged relief of postsurgical visceral pain in rats. Comp. Med. 53, 270–279 (2003).
Clark, M.D. et al. Evaluation of liposome-encapsulated oxymorphone hydrochloride in mice after splenectomy. Comp. Med. 54, 558–563 (2004).
Smith, L.J. et al. Pharmacokinetics of a controlled-release liposome-encapsulated hydromorphone administered to healthy dogs. J. Vet. Pharmacol. Ther. 31, 415–422 (2008).
Krugner-Higby, L. et al. Experimental pharmacodynamics and analgesic efficacy of liposome-encapsulated hydromorphone in dogs. J. Am. Anim. Hosp. Assoc. 47, 185–195 (2011).
Krugner-Higby, L. et al. Pharmacokinetics and behavioral effects of an extended-release, liposome-encapsulated preparation of oxymorphone in rhesus macaques. J. Pharmacol. Exp. Ther. 330, 135–141 (2009).
Krugner-Higby, L. et al. Pharmacokinetics and behavioral effects of liposomal hydromorphone suitable for perioperative use in rhesus macaques. Psychopharmacology (Berl.) 216, 511–523 (2011).
Higuchi, T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci. 52, 1145–1149 (1963).
Liechty, W.B., Kryscio, D.R., Slaughter, B.V. & Peppas, N.A. Polymers for drug delivery systems. Annu. Rev. Chem. Biomol. Eng. 1, 149–173 (2010).
Carbone, E.T., Lindstrom, K.E., Diep, S. & Carbone, L. Duration of action of sustained-release buprenorphine in 2 strains of mice. J. Am. Assoc. Lab. Anim. Sci. 51, 815–819 (2012).
Foley, P.L., Liang, H. & Crichlow, A.R. Evaluation of a sustained-release formulation of buprenorphine for analgesia in rats. J. Am. Assoc. Lab. Anim. Sci. 50, 198–204 (2011).
Chum, H. et al. Analgesic effects of sustained release buprenorphine in an incisional model of hyperalgesia in rats (Rattus norvegicus). AALAS National Meeting, Minneapolis, MN, 4–8 November 2012.
Catbagan, D.L., Quimby, J.M., Mama, K.R., Rychel, J.K. & Mich, P.M. Comparison of the efficacy and adverse effects of sustained-release buprenorphine hydrochloride following subcutaneous administration and buprenorphine hydrochloride following oral transmucosal administration in cats undergoing ovariohysterectomy. Am. J. Vet. Res. 72, 461–466 (2011).
Nunamaker, E.A. et al. Pharmacokinetics of 2 formulations of buprenorphine in macaques (Macaca mulatta and Macaca fascicularis). J. Am. Assoc. Lab. Anim. Sci. 52, 48–56 (2013).
Pontani, R.B. & Misra, A.L. A long-acting buprenorphine delivery system. Pharmacol. Biochem. Behav. 18, 471–474 (1983).
Forbes, N. et al. Morbidity and mortality rates associated with serial bleeding from the superficial temporal vein in mice. Lab Anim. (NY) 39, 236–240 (2010).
Flecknell, P.A. Analgesia of small mammals. Vet. Clin. North Am. Exot. Anim. Pract. 4, 47–56 (2001).
Abelson, A.L. et al. Use of wound soaker catheters for the administration of local anesthetic for post-operative analgesia: 56 cases. Vet. Anaesth. Analg. 36, 597–602 (2009).
Armitage-Chan, E. Use of wound soaker catheters in pain management. In Practice 35, 24–29 (2013).
Hutchings, D.E., Zmitrovich, A.C., Hamowy, A.S. & Liu, P.Y. Prenatal administration of buprenorphine using the osmotic minipump: a preliminary study of maternal and offspring toxicity and growth in the rat. Neurotoxicol. Teratol. 17, 419–423 (1995).
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Foley, P. Current options for providing sustained analgesia to laboratory animals. Lab Anim 43, 364–371 (2014). https://doi.org/10.1038/laban.590
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DOI: https://doi.org/10.1038/laban.590