References on the Administration of Analgesics Using ALZET® Osmotic Pumps

1. Acetylsalicylic Acid

8776 Adamek, A., Hu, K., Bayer, B., Wagner, H., Ertl, G., Bauersachs, J., Frantz, S. High dose aspirin and left ventricular remodeling after myocardial infarction. Basic Research In Cardiology 2007; 102(-4-):334-340. >>> Acetylsalicylic acid, lysine; Saline; SC; Mice; 2002; Controls received mp w/ placebo; functionality of mp verified by serum salicylate concentrations; pumps replaced after 2 weeks; cardiovascular; ischemia (cardiac); animal info (female, C57BL/6, 8-12 weeks old, 20-25 grams); MI induced by coronary artery ligation.

4940 Yuan, M, Konstantopoulos, N, Lee, J, Hansen, L, Li, Z.-W, Karin, M, Shoelson, S.E. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkb. Science 2001; 293(--):1673-1677. >>> Acetylsalicylic acid; salicylate, sodium; SC; Rat; mice; 2002; 2ML2; Controls received mp w/ vehicle; 2ML2 used in rats, 2002 used in mice; acetylsalicylic acid also called aspirin: dose was 120 mg/kg/day; diabetes (type II).

455 Oshima, T., McCluskey, E.R., Honda, A., Needleman, P. Pharmacological manipulation of canine cyclooxygenase and thromboxane synthetase in vivo: differential renal and platelet recovery rates. J. Pharmacol. Exp. Ther 1984; 229(-2-):598-602. >>> Acetylsalicylic acid; DMSO; Saline; IV (superficial cervical vein); dog; 2ML1; pumps primed for 4 hrs. before implant; used prefilled catheter in vein; greater solubility of ASA in DMSO allowed greater concentration in smaller total volume.

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2. Acetylsalicylic Acid

P8555 Adamek,A., Hu,K., Bayer,B., Wagner,H., Ertl,G., Bauersachs,J., Frantz,S. High dose aspirin and left ventricular remodeling after myocardial infarction. Basic Research In Cardiology 2007; 102(-4-):334-340. >>> Acetylsalicylic acid, lysine; Saline; SC; Mice; 2002; 4 weeks; Controls received mp w/ placebo; functionality of mp verified by serum salicylate concentrations; pumps replaced after 2 weeks; cardiovascular; ischemia (cardiac); animal info (female, C57BL/6, 8-12 weeks old, 20-25 grams); MI induced by coronary artery ligation.

P4829 Yuan,M, Konstantopoulos,N, Lee,J, Hansen,L, Li,Z.-W, Karin,M, Shoelson,S.E. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkb. Science 2001; 293(--):1673-1677. >>> Acetylsalicylic acid; salicylate, sodium; SC; Rat; mice; 2002; 2ML2; 3-4 weeks; Controls received mp w/ vehicle; 2ML2 used in rats, 2002 used in mice; acetylsalicylic acid also called aspirin: dose was 120 mg/kg/day; diabetes (type II).

P0455 Oshima,T., McCluskey,E.R., Honda,A., Needleman,P. Pharmacological manipulation of canine cyclooxygenase and thromboxane synthetase in vivo: differential renal and platelet recovery rates. J.Pharmacol.Exp.Ther. 1984; 229(-2-):598-602. >>> Acetylsalicylic acid; DMSO; Saline; IV (superficial cervical vein); dog; 2ML1; 3 days; pumps primed for 4 hrs. before implant; used prefilled catheter in vein; greater solubility of ASA in DMSO allowed greater concentration in smaller total volume.

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3. Alfentanil

1206 Fujinaga, M., Mazze, R.I., Jackson, E.C., Baden, J.M. Reproductive and teratogenic effects of sufentanil and alfentanil in sprague-dawley rats. Anesth. Analg 1988; 67(--):166-169. >>> Alfentanil; Sufentanil; Saline; SC; rat (pregnant); 2ML2; controls received mp w/ saline; dose-response (text); 3 doses of sufentanil infused; agents infused separately; author states'in terms of experimental design, the cost of using sc implanted osmotic minipumps is small'; teratology.

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4. Aminopyrine

3502 Kuwahara, S.K., Shinn, T.J., Schreider, B.D., Phan, M.L., Kotake, A.N. Aminopyrine infusion breath test for the determination of changes in P450 metabolism in vivo. Xenobiotica 1995; 25(-9-):973-980. >>> Aminopyrine; Formate, sodium; radio-isotopes; 14C tracer; water, acidified; NaOH; SC; rat; 2001; stability of [N-dimethyl-14C] aminopyrine verified by radiochromatographic analysis- no decomposition observed.

1268 Azri, S., Renton, K.W. Depression of murine hepatic mixed function oxidase during infection with listeria monocytogenes. J. Pharmacol. Exp. Ther 1987; 234(-3-):1089-1093. >>> Aminopyrine; Radio-isotopes; 14C tracer; Saline; SC; mice; 2002; animals infected with listeria monocytogenes.

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5. Antipyrine

592 Sendelbeck, S.L., Urquhart, J. Spatial distribution of dopamine, methotrexate and antipyrine during continuous intracerebral microperfusion. Brain Research 1985; 328(--):251-258. >>> Antipyrine; Dopamine HCl; Methotrexate, sodium; Radio-isotopes; 14C tracer; 3H tracer; CSF, artificial; Sodium fluorescein; CSF/CNS (diencephalon); rabbit; 2001; comparison of agents effects; mp primed in saline 16 hr. prior to implant; stability of labelled&unlabelled Dop.&MTX tested by paper chromat. after 7 days at 37C; brain tissue distribution;.

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6. Buprenorphine

15934 Mundt, Sarah, Marcus Groettrup, and Michael Basler. Analgesia in mice with experimental meningitis reduces pain without altering immune parameters. Altex 2015; 32(-3-):183-189. >>> Buprenorphine; SC; Mice; 1007D; Controls received mp w/ PBS; animal info (female, C57BL6, 8 weeks old); behavioral testing (pain score);“we used subcutaneously implanted ALZET®osmotic pumps to apply the analgesic buprenorphine. We ob¬served strongly reduced pain scores in diseased mice receiving analgesics, whereas the immune response was not altered in these mice. Hence, our study offers a new treatment option to improve wellbeing of mice used to study LCMV-induced meningitis without grossly altering immune parameters” pg 184;"In this study, we subcutane¬ously implanted ALZET®osmotic pumps releasing the anal¬gesic agent buprenorphine. Continuous delivery with osmotic pumps ensures constant compound levels for maximized thera-peutic efficacy and reduced adverse effects. Additionally, un¬necessary stressful animal handling due to repeated injection is not required."pg 188; Dose (0.15 mg/kg/day);.

15771 Rob Hill, Abi Lyndon, Sarah Withey, Joanne Roberts, Yvonne Kershaw, John MacLachlan, Anne Lingford-Hughes, Eamonn Kelly, Chris Bailey, Matthew Hickman, Graeme Henderson. Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine. Neuropsychopharmacology 2016; 41(--):762-773. >>> Buprenorphine; methadone; Saline; SC; Mice; Controls received mp w/ vehicle; animal info (male, CD-1, 30g); behavioral testing (tail flick latencies, mouse locomotion); dependence; Dose (Buprenorphine 5 mg/kg/day; methadone 60 mg/kg/day);.

11097 Yamdeu, R.S., Shaqura, M., Mousa, S.A., Schaefer, M., Droese, J. p38 Mitogen-activated Protein Kinase Activation by Nerve Growth Factor in Primary Sensory Neurons Upregulatesμ-Opioid Receptors to Enhance Opioid Responsiveness Toward Better Pain Control. Anesthesiology 2011; 114(-1-):150-161. >>> Fentanyl propionanilide; buprenorphine hydrochloride; Saline, isotonic; CSF/CNS (intrathecal); Rat; Controls received mp w/ vehicle; animal info (male Wistar, 200-250 g); pain.

10049 Virk, M.S., Arttamangkul, S., Birdsong, W.T., Williams, J.T. Buprenorphine Is a Weak Partial Agonist That Inhibits Opioid Receptor Desensitization. Journal of Neuroscience 2009; 29(-22-):7341-7348. >>> Buprenorphine; DMSO; water; Rat; 2ML1; Controls received mp w/ vehicle; functionality of mp verified by plasma drug levels; animal info (male, Sprague Dawley, 150-200 g.); 40% DMSO used;"the osmotic minipump delivered buprenorphine efficiently and predictably"pg. 7342.

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7. Butorphanol

16108 Meredith M. Clancy DVM, MPH, Butch KuKanich DVM, PhD, John M. Sykes IV DVM. Pharmacokinetics of butorphanol delivered with an osmotic pump during a seven-day period in common peafowl (Pavo cristatus). American Journal of Veterinary Research 2015; 76(-12-):1070-1076. >>> Butorphanol; SC; Bird (peafowl); 2ML1; animal info: 14 healthy adult male common peafowl; functionality of mp verified by plasma levels; good methods (pg. 1071-1072);“Use of these osmotic pumps may provide options for avian analgesia.” pg 1070; analgesic administration to avian species; Pharmacokinetics; Dose: 247 ug/kg/h); Resultant plasma level ((mean, 106.4 ug/L; range, 61.8 to 133.0 ug/L)); Industry authored (Wildlife Conservation Society); Interesting (Plasma concentrations of butorphanol in common peafowl were maintained at or above reported efficacious analgesic concentrations; Use of these osmotic pumps may provide options for avian analgesia) pg. 1070.

12097 Mitra, A., Kotz, C.M., Kim, E.M., Grace, M.K., Kuskowski, M.A., Billington, C.J., Levine, A.S. Effects of butorphanol on feeding and neuropeptide Y in the rat. Pharmacology Biochemistry and Behavior 2012; 100(-3-):575-580. >>> Butorphanol tartrate; SC; Rat; 2ML1; Controls received mp w/ saline; animal info (Sprague Dawley, male, 302 g);"Implantation of the pumps took less than 1 min per rat, and the length of the anesthesia was approximately 5 min per rat."pg 576; functionality of mp verified via residual volume.

9568 Tian, Y.H., Lee, K.W., You, I.J., Lee, S.Y., Jang, C.G. 7-nitroindazole, nitric oxide synthase inhibitor, attenuates physical dependence on Butorphanol in rat. Synapse 2008; 62(-8-):582-589. >>> Butorphanol tartrate; nitroindazole, 7-; Saline; DMSO; CSF/CNS; Rat; 2001; Enzyme inhibitor (nitric oxide synthase, NOS); animal info (male, Sprague Dawley, 250-275 g.); pump connected to catheter after 1 week recovery period; 10% DMSO used; PE60 tubing used.

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8. Codeine

5028 Chew, M., White, J.M., Somogyi, A.A., Bochner, F., Irvine, R.J. Precipitated withdrawal following codeine administration is dependent on CYP genotype. European Journal of Pharmacology 2001; 425(--):159-164. >>> Morphine tartrate; Codeine phosphate; Saline; SC; rat; 2ML1; functionality of mp verified by plasma drug levels; dose response (graphs p. 161); dependence.

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9. F13640

9154 Deseure, K., Breand, S., Colpaert, F.C. Curative-like analgesia in a neuropathic pain model: Parametric analysis of the dose and the duration of treatment with a high-efficacy 5-HT1A receptor agonist. European Journal of Pharmacology 2007; 568(-1-3-):134-141. >>> F13640; Acetate buffer; water, sterile; SC; Rat; 2ML1; 2ML2; 2ML4; Controls received mp w/ vehicle; dose-response (fig. 2); long-term study; pumps replaced; half-life (p. 139) 2.5 hrs. in rat plasma; multiple pumps per animal (2); post op. care (Na ampicillin); animal info (male, Sprague Dawley, 220-240 g., intraorbital nerve ligation).

7885 Colpaert, F.C., Deseure, K., Stinus, L., Adriaensen, H. High-efficacy 5-hydroxytryptamine 1A receptor activation counteracts opioid hyperallodynia and affective conditioning. Journal of Pharmacology and Experimental Therapeutics 2006; 316(-2-):892-899. >>> F13640; morphine, HCl; Saline; SC; Rat; 2ML2; Controls received mp w/ vehicle; long-term study; pumps replaced every two weeks; multiple pumps per animal (2); animal info (male, Sprague-Dawley, 220-240 g); during pump replacement a new incision was made about 1 cm away from the previous incision.

7011 Colpaert, F.C., Wu, W.P., Hao, J.X., Royer, I., Sautel, F., Wiesenfeld-Hallin, Z., Xu, X.J. High-efficacy 5-HT1A receptor activation causes a curative-like action on allodynia in rats with spinal cord injury. European Journal of Pharmacology 2004; 497(-1-):29-33. >>> F13640; SC; Rat; 2ML4; Controls received mp w/ saline; functionality of mp verified by plasma levels; long-term study; pumps replaced at day 28; 5-HT1A receptor agonist; spinal cord injury; pain.

6845 Colpaert, F.C., Tarayre, J.P., Koek, W., Pauwels, P.J., Bardin, L., Xu, X.J., Wiesenfeld-Hallin, Z., Cosi, C., Carilla-Durand, E., Assie, M.B., Vacher, B. Large-amplitude 5-HT1A receptor activation: a new mechanism of profound, central analgesia. Neuropharmacology 2002; 43(-6-):945-958. >>> F13640; morphine HCL; imipramine HCl; ketamine HCl; gabapentin; Water, double distilled; SC; Rat; 2ML2; Controls received mp w/ saline; dose-response (fig. 3); comparison of IP&SC injections vs. mp; tolerance; dependence;"Continuous F 13640 infusion uniquely produced profound analgesia in this model of severe, chronic pain."(p. 955).

6399 Wu, W.P., Hao, J.X., Xu, X.J., Wiesenfeld-Hallin, Z., Koek, W., Colpaert, F.C. The very-high-efficacy 5-HT1A receptor agonist, F 13640, preempts the development of allodynia-like behaviors in rats with spinal cord injury. European Journal of Pharmacology 2003; 478(-2-3-):131-137. >>> F13640; SC; Rat; 2ML4; Controls received mp w/ saline; functionality of mp verified by F13640 plasma levels; long-term study; pumps replaced (after 28 days).

6062 Deseure, K., Koek, W., Adriaensen, H., Colpaert, F.C. Continuous administration of the 5-hydroxytryptamine 1A agonist (3-ch loro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl]-methadone (F 13640) attenuates allodynia-like behavior in a rat model of trigeminal neuropathic pain. Journal of Pharmacology and Experimental Therapeutics 2003; 306(-2-):505-514. >>> F13640; F13714; morphine; baclofen; Saline; SC; Rat; 2ML2; Controls received mp w/ vehicle; Post Op. Care (aerosol bandage applied to protect against bacterial contamination); F13640 is a novel analgesic&5-HT1A receptor agonist; behavorial study; F13640, F13714&morphine were infused in one pump; baclofen infused in two pumps due to limited solubility.

5867 Slot, L.A.B., Koek, W., Tarayre, J.P., Colpaert, F.C. Tolerance and inverse tolerance to the hyperalgesic and analgesic actions, respectively, of the novel analgesic, F 13640. European Journal of Pharmacology 2003; 466(-3-):271-279. >>> F13640; Water, distilled; SC; Rat; 2ML2; Controls received mp w/ saline; dose-response (Fig.2; p.275); pumps replaced every week, F13640 is a novel analgesic; serotonin receptor agonist; post op. care (the site of pump emplacement was massaged daily to avoid tissue adherence).

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10. Fentanyl

16259 Anand, J. P., Boyer, B. T., Mosberg, H. I., Jutkiewicz, E. M. The behavioral effects of a mixed efficacy antinociceptive peptide, VRP26, following chronic administration in mice. Psychopharmacology (Berl) 2016; 233(-13-):2479-87. >>> VRP26, Fentanyl; Saline; SC; mice; 1007D; Controls received mp w/ vehicle; animal info (Male, female C57BL/6 wild-type, homozygous MOR knockout; 20-30 g, 8-16 wks); functionality of mp verified by in vitro testing (pg. 2481); dose-response (pg 2481); good methods (pg 2481); behavioral testing (tail suspension test, conditioned place preference and locomotor acitivities); behavioral testing (tail suspension test, conditioned place preference and locomotor acitivities); peptides; Primed for 4 hours, 37 degree Saline; antinociceptive peptide; Dose (0.3 mg/kg/day fentanyl or 10 mg/kg/day VRP26);.

13868 Mitzelfelt, J.D., Carter, C.S., Morgan, D. Thermal sensitivity across ages and during chronic fentanyl administration in rats. Psychopharmacology 2014; 231(-1-):75-84. >>> Fentanyl; Saline; SC; Rat; 2ML4; Controls received mp w/ vehicle; animal info (male, Fischer 344 x Brown Norway, 16, 20 and 24 months old); behavioral testing (temperature preference/heat and cold sensitvity, locomotor activity); Pumps removed after 4 weeks;.

11097 Yamdeu, R.S., Shaqura, M., Mousa, S.A., Schaefer, M., Droese, J. p38 Mitogen-activated Protein Kinase Activation by Nerve Growth Factor in Primary Sensory Neurons Upregulatesμ-Opioid Receptors to Enhance Opioid Responsiveness Toward Better Pain Control. Anesthesiology 2011; 114(-1-):150-161. >>> Fentanyl propionanilide; buprenorphine hydrochloride; Saline, isotonic; CSF/CNS (intrathecal); Rat; Controls received mp w/ vehicle; animal info (male Wistar, 200-250 g); pain.

11036 Mitzelfelt, J.D., DuPree, J.P., Seo, D.O., Carter, C.S., Morgan, D. Effects of chronic fentanyl administration on physical performance of aged rats. Experimental Gerontology 2011; 46(-1-):65-72. >>> Fentanyl; SC; Rat; 2ML4; Controls received mp w/ saline; animal info (male, Fisher 344 x Brown Norway, 12, 24, 30 mo old); behavioral testing (open field activity, grip strength, rotarod).

10986 Raehal, K.M., Bohn, L.M. The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics. Neuropharmacology 2011; 60(-1-):58-65. >>> Morphine; methadone; fentanyl; oxycodone; Water, sterile, distilled; SC; Mice; Animal info (male, WT, barr2-KO); dependence; wound clips used.

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11. Flupirtine

T0009 Kistler,P. Zur schmerzbekampfung im tierversuch: Eine studie zur wahl geeigneter analgetika fur die schmerzbekampfung bei versuchstieren. Dissertation, Universitat Bern, Zurich 1988; (--):-. >>> D16949; Flupirtine; Tramadol; Buprenorphine; Nalbuphine; SC; mice; rat; 2-7 weeks; German with English abstract (p. 7), pump cross-section and dimensions (pg. 94).

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12. Hydromorphone

13837 Koesters, A., Engisch, K.L., Rich, M.M., Rich, M.M. Decreased cardiac excitability secondary to reduction of sodium current may be a significant contributor to reduced contractility in a rat model of sepsis. CRITICAL CARE 2014; 18(--):U351-U357. >>> Hydromorphone; IP; Rat; Animal info (female, Wistar, adult, 250-300g); post op. care (buprenorphine 0.12 mg/kg SC injection); used 2ML size pump; pain relief;.

9397 Kumar, P., Sunkaraneni, S., Sirohi, S., Dighe, S.V., Walker, E.A., Yoburn, B.C. Hydromorphone efficacy and treatment protocol impact on tolerance and mu-opioid receptor regulation. European Journal of Pharmacology 2008; 597(-1-3-):39-45. >>> Hydromorphone; Saline; SC; Mice; 2001; Controls received inert placebo pellet; tolerance; animal info (male, Swiss Webster, 22-30 g.);"There was substantially more tolerance with infusion treatment compared to injection treatment."pg. 43.

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13. Indomethacin

15049 Na, Y.R., Yoon, Y.N., Son, D., Jung, D., Gu, G.J., Seok, S.H., Seok, S.H. Consistent Inhibition of Cyclooxygenase Drives Macrophages towards the Inflammatory Phenotype. PLoS One 2015; 10(--):U1730-U1742. >>> NA-398; SC-560; indomethacin; DMSO; SC; Mice; Controls received mp w/ vehicle; animal info (female, BALB/c); immunology;.

4929 Babin, M.C., Ricketts, K., Skvorak, J.P., Gazaway, M., Mitcheltree, L.W., Casillas, R.P. Systemic administration of candidate antivesicants to protect against topically applied suitor mustard in the mouse ear vesicant model (MEVM ).. Journal of Applied Toxicology 2000; 20(--):S141-S144. >>> Hydrocortisone; indomethacin; olvanil; PEG 200; SC; mice; Controls received mp w/ vehicle; toxicology.

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14. Ketorolac

9053 Scarlett, J.M., Jobst, E.E., Enriori, P.J., Bowe, D.D., Batra, A.K., Grant, W.F., Cowley, M.A., Marks, D.L. Regulation of central melanocortin signaling by interleukin-1beta. Endocrinology 2007; 148(-9-):4217-4225. >>> Ketorolac; Saline, sterile; SC; Mice; 1007D; Controls received mp w/ vehicle; animal info (male, C57BL/6J, 4-5 wks old).

5217 Southall, M.D., Bolyard, L.A., Vasko, M.R. Twenty-four hour exposure to prostaglandin downregulates prostanoid receptor binding but does not alter PGE(2)-mediated sensitization of rat sensory neurons. Pain 2002; 96(--):285-296. >>> Ketorolac tromethamine; Saline; CSF/CNS (intrathecal); rat; 2001; controls received mp w/ vehicle; ketorolac is an NSAID sold as Toradol; cannula patency verfied by saline injection.

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15. Levorphanol

2501 Teskey, G.C., Kavaliers, M. Modifications of social conflict-induced analgesic and activity responses in male mice receiving chronic opioid agonist and antagonist treatments. Pharmacol. Biochem. Behav 1991; 38(--):485-493. >>> Levorphanol tartrate; Naltrexone HCl; U-50,488H; ICI-154,129; Saline; IP; mice; 2001; functionality of mp verified by measuring residual pump volume; tolerance.

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16. Lofentanil

S0190 Cowan,A., August,D., Harp,J.R., Carlsson,C., Smith,D.S. Acute physical dependence in rats: a comparison of fentanyl, lofentanil and sufentanil. Fed.Proc. 1982; 41(-4-):1220-. >>> Lofentanil; Fentanyl; Sufentanil; SC; rat; 2001; 6 hours; no comment posted.

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17. Meperidine

3663 Paronis, C.A., Holtzman, S.G. Sensitization and tolerance to the discriminative stimulus effects of mu-opioid agonists. Psychopharmacology 1994; 114(--):601-610. >>> Naloxone HCl; Morphine sulfate; Meperidine HCl; Fentanyl citrate; Saline; SC; rat; 2ML1; controls received sham pumps; tolerance.

2469 Paronis, C.A., Holtzman, S.G. Development of tolerance to the analgesic activity of mu agonists after continuous infusion of morphine, meperidine or fentanyl in rats. J. Pharmacol. Exp. Ther 1992; 262(-1-):1-9. >>> Morphine; Meperidine; Fentanyl; Saline; SC; rat; 2ML1; tolerance.

588 Schmidt, W.K., Tam, S.W., Shotzberger, G.S., Smith Jr, D.H., Clark, R., Vernier, V.G. Nalbuphine. Drug Alcohol Depend 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

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18. Methadone

15771 Rob Hill, Abi Lyndon, Sarah Withey, Joanne Roberts, Yvonne Kershaw, John MacLachlan, Anne Lingford-Hughes, Eamonn Kelly, Chris Bailey, Matthew Hickman, Graeme Henderson. Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine. Neuropsychopharmacology 2016; 41(--):762-773. >>> Buprenorphine; methadone; Saline; SC; Mice; Controls received mp w/ vehicle; animal info (male, CD-1, 30g); behavioral testing (tail flick latencies, mouse locomotion); dependence; Dose (Buprenorphine 5 mg/kg/day; methadone 60 mg/kg/day);.

14452 Vestal-Laborde, A.A., Eschenroeder, A.C., Bigbee, J.W., Robinson, S.E., Sato-Bigbee, C., Sato-Bigbee, C. The Opioid System and Brain Development: Effects of Methadone on the Oligodendrocyte Lineage and the Early Stages of Myelination. Developmental Neuroscience 2014; 36(--):409-421. >>> Methadone; Saline; SC; Rat (pregnant); 2ML4; Controls received mp w/ vehicle; animal info (female, Pregnant, Sprague Dawley, GD7); teratology; dependence;.

13924 Schreiber, S., Barak, Y., Hostovsky, A., Baratz-Goldstein, R., Volis, I., Rubovitch, V., Pick, C.G. Interaction of Different Antidepressants with Acute and Chronic Methadone in Mice, and Possible Clinical Implications. Journal of Molecular Neuroscience 2014; 52(-4-):598-604. >>> Methadone; SC; Mice; 1007D; Animal info (male, ICR, 25-35g); behavioral testing (hot plate); dependence;.

10986 Raehal, K.M., Bohn, L.M. The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics. Neuropharmacology 2011; 60(-1-):58-65. >>> Morphine; methadone; fentanyl; oxycodone; Water, sterile, distilled; SC; Mice; Animal info (male, WT, barr2-KO); dependence; wound clips used.

10943 Quillinan, N., Lau, E.K., Virk, M., von Zastrow, M., Williams, J.T. Recovery from mu-Opioid Receptor Desensitization after Chronic Treatment with Morphine and Methadone. Journal of Neuroscience 2011; 31(-12-):4434-4443. >>> Morphine; methadone; Water; SC; Rat; 2ML1; 2001; Controls received mp w/ vehicle; tolerance; animal info (adult (150-250 g, male, Sprague Dawley).

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19. Morphine

16353 Gong, K., Bhargava, A., Jasmin, L. GluN2B N-methyl-D-aspartate receptor and excitatory amino acid transporter 3 are upregulated in primary sensory neurons after 7 days of morphine administration in rats: implication for opiate-induced hyperalgesia. Pain 2016; 157(-1-):147-58. >>> Morphine; Ro 25-6981; Saline; SC; Rat; 2ML1; Controls received mp w/ vehicle; animal info (Male Sprague-dawley rats, 220-250 g); functionality of mp verified by behavioral tests; good methods (pg. 148); post op. care (opiate administration using pumps); behavioral testing (Hargreaves plantar test); Dependence/tolerance induced; Opiate use; Dose ( 15 mg/ml Morphine, 5 mg/kg Ro 25-6981);.

16138 Nardelli, P., Vincent, J. A., Powers, R., Cope, T. C., Rich, M. M. Reduced motor neuron excitability is an important contributor to weakness in a rat model of sepsis. Exp Neurol 2016; 282(--):1-8. >>> Oxymorphine; IP; Rat; post op. care (buprenorphine SC 0.12 mg/kg; 5 ml SC saline; Baytril SC 10 mg/kg Q12H); used 2ML size; pumps used for continuous pain relief in rat sepsis model; Dose (30 ug/kg/h);.

16076 Zadina, J. E., Nilges, M. R., Morgenweck, J., Zhang, X., Hackler, L., Fasold, M. B. Endomorphin analog analgesics with reduced abuse liability, respiratory depression, motor impairment, tolerance, and glial activation relative to morphine. Neuropharmacology 2016; 105(--):215-27. >>> Morphine; endomorphine analog; Saline; CSF/CNS (intrathecal); rat; 2001; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 250-400g); half-life (p. 219); behavioral testing (tail flick test; rotarod testing); stability verified by (internal testing; stability>1 year at 37C); pumps primed in 37C saline for 16 hours; used PE-8 IT catheter; Dose (2 ug/hr morphine; 0.056-0.075 ug/hr analog);.

16047 Tsai, R. Y., Wang, J. C., Chou, K. Y., Wong, C. S., Cherng, C. H. Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression. J Formos Med Assoc 2016; 115(-6-):445-54. >>> Morphine; CSF/CNS (intrathecal); Rat; Controls received mp w/ saline; animal info (male, Wistar); behavioral testing (tail-flick); Dose (15 ug/h);.

16033 Rakesh Kumar,, K. H. Reeta,, Subrata Basu Ray. Chronic Spinal Infusion of Loperamide Alleviates Postsurgical Pain in Rats. Indian Journal of Experimental Biology 2014; 52(--):317-322. >>> loperamide; morphine; PEG, saline, ethanol; CSF/CNS (intrathecal); rat; 2ML2; Controls received mp w/ vehicle; animal info (adult male Sprague-dawley rats, 275-350 g); dose-response (pg 319, 320); good methods (pg. 317-318); post op. care (neomycin ointment and perioperative ketoprofen [3 mg/kg, im] given); behavioral testing (stepping placing, righting reflex, and Hargreaves paw withdrawal test); delayed delivery (lynch coil filled with saline used to delay administration of drug by 3 days; ); Dose: Morphine and Loperamide ( 0.5,1, and 2 uL/hr).

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20. Nalbuphine

9203 Jang, S., Kim, H., Kim, D., Jeong, M.W., Ma, T., Kim, S., Ho, I.K., Oh, S. Attenuation of morphine tolerance and withdrawal syndrome by coadministration of nalbuphine. ARCHIVES OF PHARMACAL RESEARCH 2006; 29(-8-):677-684. >>> Morphine chloride; nalbuphine HCl; Saline; CSF/CNS; Rat; 2001; Controls received mp w/ vehicle; comparison of IP injections vs. mp; tolerance; dependence; animal info (male, Sprague Dawley, 220-240 g.).

588 Schmidt, W.K., Tam, S.W., Shotzberger, G.S., Smith Jr, D.H., Clark, R., Vernier, V.G. Nalbuphine. Drug Alcohol Depend 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

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21. Naproxen

15192 Baj-Rossi, C., Jost, T.R., Cavallini, A., Grassi, F., De Micheli, G., Carrara, S. Continuous monitoring of Naproxen by a cytochrome P450-based electrochemical sensor. BIOSENSORS&BIOELECTRONICS 2014; 53(-;-):283-287. >>> Naproxen; Methanol; In Vitro; 1002; Functionality of mp verified by naproxen levels measured with sensors;.

14565 Rosa, A.C., Pini, A., Lucarini, L., Lanzi, C., Veglia, E., Thurmond, R.L., Stark, H., Masini, E., Masini, E. Prevention of Bleomycin-Induced Lung Inflammation and Fibrosis in Mice by Naproxen and JNJ7777120 Treatment. Journal of Pharmacology and Experimental Therapeutics 2014; 351(--):308-316. >>> JNJ7777120; naproxen; SC; Mice; 1004; Control animals received mp w/ vehicle; animal info (male, C57BL/6, ~2 mo old, 25-30 g); infusion rate listed as 0.11 ul/hr; JNJ7777120 also known as (1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine), is a selective H4R antagonist; one group received combination of JNJ7777120 and naproxen.

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22. Normorphine

173 Schulz, R., Wuster, M. Are there sybtypes (isoreceptors) of multiple opiate receptors in the mouse vas deferens. Eur. J. Pharmacol 1981; 76(--):61-66. >>> Endorphin, a-neo-; DsThr; Dynorphin; Enkephalin analog DADLE; FK-33824; MR-2034; MRZ; Normorphine; Sufentanil; Water; SC; mice; 2001; peptides; MRZ is 5,9-dimethyl,2'S-5,9-dimethyl-2'-hydroxy-2-(2-methoxy-propyl)-6,7-benzomorphan, a kappa opioid agonist.

170 Schulz, R., Wuster, M., Rubini, P., Herz, A. Functional opiate receptors in the guinea-pig ileum: their differentiation by means of selective tolerance development. J. Pharmacol. Exp. Ther 1981; 219(-2-):547-550. >>> DsThr; Enkephalin agonist DADL; Fentanyl; FK-33824; MR-2034; MRZ; Normorphine; Water; SC; guinea-pig; 2001; peptides.

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23. Oxymorphone

9831 Novak, K.R., Nardelli, P., Cope, T.C., Filatov, G., Glass, J.D., Khan, J., Rich, M.M. Inactivation of sodium channels underlies reversible neuropathy during critical illness in rats. Journal of Clinical Investigation 2009; 119(-5-):1150-1158. >>> Oxymorphone; IM (abdominal); Rat; Post op. care (buprenorphine); animal info (female, Wistar, 250-300g).

5003 Gillingham, M.B., Clark, M.D., Dahly, E.M., Krugner-Higby, L.A., Ney, D.M. A comparison of two opioid analgesics for relief of visceral pain induced by intestinal resection in rats. CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE 2001; 40(-1-):21-26. >>> Oxymorphone HCl; IP; rat; functionality of mp verified by pain relief indicators - posture, physical condition, behavior; comparison of iv infusions vs mp; compared bolus iv infusion, continuous iv infusion, osmotic pump..

588 Schmidt, W.K., Tam, S.W., Shotzberger, G.S., Smith Jr, D.H., Clark, R., Vernier, V.G. Nalbuphine. Drug Alcohol Depend 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

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24. Pentazocine

3567 Bergeron, R., de Montigny, C., Debonnel, G. Effect of short-term and long-term treatments with sigma ligands on the N-methyl-D-aspartate response in the CA(3) region of the rat dorsal hippocampus. Br. J. Pharmacol 1997; 120(--):1351-1359. >>> Haloperidol; JO-1784; Pentazocine; DTG; SC; rat; controls received mp w/saline; DTG is di(2-tolyl)guanidin.

1907 Weissman, A.D., De Souza, E.B. Chronic treatment of rats with the specific sigma ligand D-pentazocine fails to modulate dopamine D2 and sigma binding in brain. Eur. J. Pharmacol 1991; 195(--):163-165. >>> Pentazocine, d-; Saline; SC; rat; 2ML4; no comment posted.

588 Schmidt, W.K., Tam, S.W., Shotzberger, G.S., Smith Jr, D.H., Clark, R., Vernier, V.G. Nalbuphine. Drug Alcohol Depend 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

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25. Propoxyphene

588 Schmidt, W.K., Tam, S.W., Shotzberger, G.S., Smith Jr, D.H., Clark, R., Vernier, V.G. Nalbuphine. Drug Alcohol Depend 1985; 14(--):339-362. >>> Ethylketocyclazocine; Heroin; Meperidine; Oxymorphone; Pentazocine; Propoxyphene; Bremazocine; Buprenorphine; Butorphanol; Methadone; Morphine; Nalbuphine; U-50,488H; SC; mice; comparison of sc morphine pellets vs. mp infusion; comparison of agents effects; controls received unspecified placebo infusion.

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26. Sodium Salicylate

4940 Yuan, M, Konstantopoulos, N, Lee, J, Hansen, L, Li, Z.-W, Karin, M, Shoelson, S.E. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkb. Science 2001; 293(--):1673-1677. >>> Acetylsalicylic acid; salicylate, sodium; SC; Rat; mice; 2002; 2ML2; Controls received mp w/ vehicle; 2ML2 used in rats, 2002 used in mice; acetylsalicylic acid also called aspirin: dose was 120 mg/kg/day; diabetes (type II).

3658 Gordon, C.J. Pharmacological analysis of diisopropyl fluorophosphate: effects on core temperature, heart rate, and motor activity in the unrestrained rat. Pharmacol. Biochem. Behav 1996; 55(-2-):185-194. >>> Scopolamine; Methylscopolamine nitrate; Salicylate, sodium; SC; rat; 2002; temperatures were taken with radiotelemetry.

1661 Bergman, K., Cekan, E., Slanina, P., Gabrielsson, J., Hellenas, K.-E. Effects of dietary sodium selenite supplementation on salicylate-induced embryo- and fetotoxicity in the rat. Toxicology 1990; 61(--):135-146. >>> Salicylate, sodium; Water; IV; rat; 2ML1; teratology.

826 Gabrielsson, J., Paalzow, L., Larsson, S., Blomquist, I. Constant rate of infusion - improvement of tests for teratogenicity and embryotoxicity. Life Sci 1985; 37(-24-):2275-2282. >>> Salicylate, sodium; IV (jugular); rat (pregnant); 2ML1; comparison of iv bolus injection vs. mp infusion; controls received mp; mp infusion during two periods of gestation; dose-response; teratology; embryotoxicity; study to determine effects on offspring.

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27. Sufentanil

4838 Diaz, A, Florez, J., Pazos, A, Hurle, M.A. Opioid tolerance and supersensitivity induce regional changes in the autoradiographic density of dihydropyridine-sensitive calcium channels in the rat central nervous system.. Pain 2000; 86(--):227-235. >>> Sufentanil citrate; Nimodipine;; Saline; Ethanol; Propylene glycol; Water;; SC;; rat;; 2001;; Controls received mp w/ vehicle; tolerance; Group 1 received vehicle alone, Group 2 received chronic sufentanil, Group 3 received sufentanil&nimodipine, Group 4 received nimodipine alone; Nimodipine is a CA2+ antagonist opioid; sufentanil citrate was diluted in saline; nimodipine was diluted in 10% ethanol / 20% propylene glycol / 70% water.

4837 Diaz, A, Pazos, A, Florez, J., Hurle, M.A. Autoradiographic mapping of m-opioid receptors during opiate tolerance and supersensitivity in the rat central nervous system.. Nauyn-Schmiedeberg's Arch Pharmacol 2000; 362(--):101-109. >>> Sufentanil citrate; Nimodipine;; Saline; Ethanol; Propylene glycol; Water;; SC;; rat;; 2001;; Controls received mp w/ vehicle; tolerance; Group 1 received sufentanil, Group 2 received sufentanil&nimodipine, Group 3 received nimodipine, Group 4 received vehicle; Nimodipine is a Ca channel blocker; sufentanil was diluted in saline; nimodipine was diluted in 10% ethanol / 20% propylene glycol / 70% water;.

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28. Tramadol

5059 Tsai, Y.C., Sung, Y.H., Chang, P.J., Kang, F.C., Chu, K.S. Tramadol relieves thermal hyperalgesia in rats with chronic constriction injury of the sciatic nerve. FUNDAMENTAL&CLINICAL PHARMACOLOGY 2000; 14(--):335-340. >>> Tramadol; Saline; SC; rat; 2ML1; controls received mp w/ vehicle; functionality of mp verified by paw withdrawal latency (analgesia index); dose-response (graph p. 337); comparison of sc injection vs. mp; analgesia..

4959 Tsai, Y.C., Won, S.J. Effects of tramadol on T lymphocyte proliferation and natural killer cell activity in rats with sciatic constriction injury. Pain 2001; 92(--):63-69. >>> Tramadol; Saline; SC; rat; 2ML1; Controls received mp w/ vehicle; comparison of sc injections vs. mp; immunology; multiple pumps per animal (2) used in high-dose groups; nociception; tramadol is a centrally acting analgesic..

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29. Zomepirac

S0199 Cowan,A., Tortella,F.C., Gmerek,D.E. EEG and behavioral studies with zomepirac sodium in rats. Pain 1981; 11(-1-):194-. >>> Zomepirac, sodium; Water; CSF/CNS; SC; rat; 2001; no duration posted; 7 days icv, 3 days sc.

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“Pump implantation and subsequent infusion of either A-CSF or PAI-1 did not impair the mice’s ability to perform a previously learned motor task.” Seeds et al., The Journal of Neuroscience 2003;23(19):7368-7375.