Refining pain management in mice by comparing multimodal analgesia and NSAID monotherapy for neurosurgical procedures.
Animals
Anti-Inflammatory Agents, Non-Steroidal
/ administration & dosage
Mice
Male
Pain Management
/ methods
Female
Mice, Inbred C57BL
Pain, Postoperative
/ drug therapy
Neurosurgical Procedures
/ adverse effects
Carbazoles
/ administration & dosage
Analgesia
/ methods
Bupivacaine
/ administration & dosage
Buprenorphine
/ administration & dosage
Analgesics, Opioid
/ administration & dosage
Drug Therapy, Combination
3R
Craniotomy
Multimodal analgesia
Postsurgical pain
Severity assessment
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
12 Aug 2024
12 Aug 2024
Historique:
received:
15
03
2024
accepted:
31
07
2024
medline:
13
8
2024
pubmed:
13
8
2024
entrez:
12
8
2024
Statut:
epublish
Résumé
While neurosurgical interventions are frequently used in laboratory mice, refinement efforts to optimize analgesic management based on multimodal approaches appear to be rather limited. Therefore, we compared the efficacy and tolerability of combinations of the non-steroidal anti-inflammatory drug carprofen, a sustained-release formulation of the opioid buprenorphine, and the local anesthetic bupivacaine with carprofen monotherapy. Female and male C57BL/6J mice were subjected to isoflurane anesthesia and an intracranial electrode implant procedure. Given the multidimensional nature of postsurgical pain and distress, various physiological, behavioral, and biochemical parameters were applied for their assessment. The analysis revealed alterations in Neuro scores, home cage locomotion, body weight, nest building, mouse grimace scales, and fecal corticosterone metabolites. A composite measure scheme allowed the allocation of individual mice to severity classes. The comparison between groups failed to indicate the superiority of multimodal regimens over high-dose NSAID monotherapy. In conclusion, our findings confirmed the informative value of various parameters for assessment of pain and distress following neurosurgical procedures in mice. While all drug regimens were well tolerated in control mice, our data suggest that the total drug load should be carefully considered for perioperative management. Future studies would be of interest to assess potential synergies of drug combinations with lower doses of carprofen.
Identifiants
pubmed: 39134625
doi: 10.1038/s41598-024-69075-2
pii: 10.1038/s41598-024-69075-2
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
carprofen
FFL0D546HO
Carbazoles
0
Bupivacaine
Y8335394RO
Buprenorphine
40D3SCR4GZ
Analgesics, Opioid
0
Types de publication
Journal Article
Comparative Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
18691Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : FOR 2591, GZ: PO681/9-2
Organisme : Deutsche Forschungsgemeinschaft
ID : FOR 2591, GZ: BA5768/2-1
Organisme : Deutsche Forschungsgemeinschaft
ID : FOR 2591, GZ: TA2072/1-1
Organisme : Deutsche Forschungsgemeinschaft
ID : FOR 2591, GZ: ME3737/24-1
Informations de copyright
© 2024. The Author(s).
Références
King, H. et al. Anesthesia and analgesia for experimental craniotomy in mice and rats: A systematic scoping review comparing the years 2009 and 2019. Front. Neurosci. 17, 1143109. https://doi.org/10.3389/fnins.2023.1143109 (2023).
doi: 10.3389/fnins.2023.1143109
pubmed: 37207181
pmcid: 10188949
Cho, C. et al. Evaluating analgesic efficacy and administration route following craniotomy in mice using the grimace scale. Sci. Rep. 9, 359. https://doi.org/10.1038/s41598-018-36897-w (2019).
doi: 10.1038/s41598-018-36897-w
pubmed: 30674967
pmcid: 6344523
Gottschalk, A. et al. Prospective evaluation of pain and analgesic use following major elective intracranial surgery. J. Neurosurg. 106, 210–216. https://doi.org/10.3171/jns.2007.106.2.210 (2007).
doi: 10.3171/jns.2007.106.2.210
pubmed: 17410701
Tennant, F. The physiologic effects of pain on the endocrine system. Pain Ther. 2, 75–86. https://doi.org/10.1007/s40122-013-0015-x (2013).
doi: 10.1007/s40122-013-0015-x
pubmed: 25135146
pmcid: 4107914
DeMarco, G. J. & Nunamaker, E. A. A review of the effects of pain and analgesia on immune system function and inflammation: relevance for preclinical studies. Comp. Med. 69, 520–534. https://doi.org/10.30802/aalas-cm-19-000041 (2019).
doi: 10.30802/aalas-cm-19-000041
pubmed: 31896389
pmcid: 6935697
Jirkof, P. & Potschka, H. Experimental Design and Reproducibility in Preclinical Animal Studies (Springer International Publishing, 2021).
Foley, P. L., Kendall, L. V. & Turner, P. V. Clinical management of pain in rodents. Comp. Med. 69, 468–489. https://doi.org/10.30802/aalas-cm-19-000048 (2019).
doi: 10.30802/aalas-cm-19-000048
pubmed: 31822323
pmcid: 6935704
Flecknell, P. Rodent analgesia: Assessment and therapeutics. Vet. J. 232, 70–77. https://doi.org/10.1016/j.tvjl.2017.12.017 (2018).
doi: 10.1016/j.tvjl.2017.12.017
pubmed: 29428096
Matsumiya, L. C. et al. Using the Mouse Grimace Scale to reevaluate the efficacy of postoperative analgesics in laboratory mice. J. Am. Assoc. Lab. Anim. Sci. 51, 42–49 (2012).
pubmed: 22330867
pmcid: 3276965
Miller, A. L., Wright-Williams, S. L., Flecknell, P. A. & Roughan, J. V. A comparison of abdominal and scrotal approach methods of vasectomy and the influence of analgesic treatment in laboratory mice. Lab. Anim. 46, 304–310. https://doi.org/10.1258/la.2012.012078 (2012).
doi: 10.1258/la.2012.012078
pubmed: 23097564
Wright-Williams, S. L., Courade, J. P., Richardson, C. A., Roughan, J. V. & Flecknell, P. A. Effects of vasectomy surgery and meloxicam treatment on faecal corticosterone levels and behaviour in two strains of laboratory mouse. Pain 130, 108–118. https://doi.org/10.1016/j.pain.2006.11.003 (2007).
doi: 10.1016/j.pain.2006.11.003
pubmed: 17196337
Jirkof, P., Tourvieille, A., Cinelli, P. & Arras, M. Buprenorphine for pain relief in mice: Repeated injections vs sustained-release depot formulation. Lab. Anim. 49, 177–187. https://doi.org/10.1177/0023677214562849 (2015).
doi: 10.1177/0023677214562849
pubmed: 25488320
Kendall, L. V. et al. Pharmacokinetics of sustained-release analgesics in mice. J. Am. Assoc. Lab. Anim. Sci. 53, 478–484 (2014).
pubmed: 25255070
pmcid: 4181689
Clark, T. S., Clark, D. D. & Hoyt, R. F. Jr. Pharmacokinetic comparison of sustained-release and standard buprenorphine in mice. J. Am. Assoc. Lab. Anim. Sci. 53, 387–391 (2014).
pubmed: 25199095
pmcid: 4113239
Drude, S. et al. Side effects of control treatment can conceal experimental data when studying stress responses to injection and psychological stress in mice. Lab. Anim. (NY) 40, 119–128. https://doi.org/10.1038/laban0411-119 (2011).
doi: 10.1038/laban0411-119
pubmed: 21427691
Schreiner, V. et al. Design and in vivo evaluation of a microparticulate depot formulation of buprenorphine for veterinary use. Sci. Rep. 10, 17295. https://doi.org/10.1038/s41598-020-74230-6 (2020).
doi: 10.1038/s41598-020-74230-6
pubmed: 33057103
pmcid: 7560740
Wolter, A. et al. A buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72 h in mouse femoral fracture models. Sci. Rep. 13, 3824. https://doi.org/10.1038/s41598-023-30641-9 (2023).
doi: 10.1038/s41598-023-30641-9
pubmed: 36882427
pmcid: 9992384
Jirkof, P. et al. Burrowing behavior as an indicator of post-laparotomy pain in mice. Front. Behav. Neurosci. 4, 165. https://doi.org/10.3389/fnbeh.2010.00165 (2010).
doi: 10.3389/fnbeh.2010.00165
pubmed: 21031028
pmcid: 2965018
Jirkof, P. et al. Assessment of postsurgical distress and pain in laboratory mice by nest complexity scoring. Lab. Anim. 47, 153–161. https://doi.org/10.1177/0023677213475603 (2013).
doi: 10.1177/0023677213475603
pubmed: 23563122
Glasenapp, A., Bankstahl, J. P., Bähre, H., Glage, S. & Bankstahl, M. Subcutaneous and orally self-administered high-dose carprofen in male and female mice: pharmacokinetics, tolerability and impact on cage-side pain indicators. Biorxiv https://doi.org/10.1101/2023.06.03.543582 (2023).
doi: 10.1101/2023.06.03.543582
Aulehner, K. et al. Grimace scale, burrowing, and nest building for the assessment of post-surgical pain in mice and rats-A systematic review. Front Vet. Sci. https://doi.org/10.3389/fvets.2022.930005 (2022).
doi: 10.3389/fvets.2022.930005
pubmed: 36277074
pmcid: 9583882
Turner, P. V., Pang, D. S. & Lofgren, J. L. A review of pain assessment methods in laboratory rodents. Comp. Med. 69, 451–467. https://doi.org/10.30802/aalas-cm-19-000042 (2019).
doi: 10.30802/aalas-cm-19-000042
pubmed: 31896391
pmcid: 6935698
Tappe-Theodor, A., King, T. & Morgan, M. M. Pros and cons of clinically relevant methods to assess pain in rodents. Neurosci. Biobehav. Rev. 100, 335–343. https://doi.org/10.1016/j.neubiorev.2019.03.009 (2019).
doi: 10.1016/j.neubiorev.2019.03.009
pubmed: 30885811
pmcid: 6528820
Langford, D. J. et al. Coding of facial expressions of pain in the laboratory mouse. Nat. Methods 7, 447–449. https://doi.org/10.1038/nmeth.1455 (2010).
doi: 10.1038/nmeth.1455
pubmed: 20453868
Lees, P., Landoni, M. F., Giraudel, J. & Toutain, P. L. Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest. J. Vet. Pharmacol. Ther. 27, 479–490. https://doi.org/10.1111/j.1365-2885.2004.00617.x (2004).
doi: 10.1111/j.1365-2885.2004.00617.x
pubmed: 15601442
van Dijk, R. M. et al. Design of composite measure schemes for comparative severity assessment in animal-based neuroscience research: A case study focussed on rat epilepsy models. PLoS One 15, e0230141. https://doi.org/10.1371/journal.pone.0230141 (2020).
doi: 10.1371/journal.pone.0230141
pubmed: 32413036
pmcid: 7228039
Reiber, M. et al. Evidence-based comparative severity assessment in young and adult mice. PLoS One 18, e0285429. https://doi.org/10.1371/journal.pone.0285429 (2023).
doi: 10.1371/journal.pone.0285429
pubmed: 37862304
pmcid: 10588901
Whittaker, A. L., Liu, Y. & Barker, T. H. Methods Used and Application of the Mouse Grimace Scale in Biomedical Research 10 Years on: A Scoping Review. Animals (Basel) https://doi.org/10.3390/ani11030673 (2021).
doi: 10.3390/ani11030673
pubmed: 34359180
Evangelista, M. C., Monteiro, B. P. & Steagall, P. V. Measurement properties of grimace scales for pain assessment in nonhuman mammals: a systematic review. Pain 163, e697–e714. https://doi.org/10.1097/j.pain.0000000000002474 (2022).
doi: 10.1097/j.pain.0000000000002474
pubmed: 34510132
Hohlbaum, K., Corte, G. M., Humpenöder, M., Merle, R. & Thöne-Reineke, C. Reliability of the Mouse Grimace Scale in C57BL/6JRj Mice. Animals (Basel) https://doi.org/10.3390/ani10091648 (2020).
doi: 10.3390/ani10091648
pubmed: 32937881
Mota-Rojas, D. et al. The Utility of Grimace Scales for Practical Pain Assessment in Laboratory Animals. Animals (Basel) https://doi.org/10.3390/ani10101838 (2020).
doi: 10.3390/ani10101838
pubmed: 33333890
Roughan, J. V. & Sevenoaks, T. Welfare and Scientific Considerations of Tattooing and Ear Tagging for Mouse Identification. J. Am. Assoc. Lab. Anim. Sci. 58, 142–153. https://doi.org/10.30802/aalas-jaalas-18-000057 (2019).
doi: 10.30802/aalas-jaalas-18-000057
pubmed: 30813985
pmcid: 6433351
Swan, J. et al. Decreased levels of discomfort in repeatedly handled mice during experimental procedures, assessed by facial expressions. Front. Behav. Neurosci. 17, 1109886. https://doi.org/10.3389/fnbeh.2023.1109886 (2023).
doi: 10.3389/fnbeh.2023.1109886
pubmed: 36873771
pmcid: 9978997
Defensor, E. B., Corley, M. J., Blanchard, R. J. & Blanchard, D. C. Facial expressions of mice in aggressive and fearful contexts. Physiol. Behav. 107, 680–685. https://doi.org/10.1016/j.physbeh.2012.03.024 (2012).
doi: 10.1016/j.physbeh.2012.03.024
pubmed: 22484562
Miller, A., Kitson, G., Skalkoyannis, B. & Leach, M. The effect of isoflurane anaesthesia and buprenorphine on the mouse grimace scale and behaviour in CBA and DBA/2 mice. Appl. Anim. Behav. Sci. 172, 58–62. https://doi.org/10.1016/j.applanim.2015.08.038 (2015).
doi: 10.1016/j.applanim.2015.08.038
pubmed: 26937061
pmcid: 4768077
Hohlbaum, K. et al. Severity classification of repeated isoflurane anesthesia in C57BL/6JRj mice-Assessing the degree of distress. PLoS One https://doi.org/10.1371/journal.pone.0179588 (2017).
doi: 10.1371/journal.pone.0179588
pubmed: 28617851
pmcid: 5472303
Durst, M. S., Arras, M., Palme, R., Talbot, S. R. & Jirkof, P. Lidocaine and bupivacaine as part of multimodal pain management in a C57BL/6J laparotomy mouse model. Sci. Rep. 11, 10918. https://doi.org/10.1038/s41598-021-90331-2 (2021).
doi: 10.1038/s41598-021-90331-2
pubmed: 34035397
pmcid: 8149411
Adamson, T. W. et al. Assessment of carprofen and buprenorphine on recovery of mice after surgical removal of the mammary fat pad. J. Am. Assoc. Lab. Anim. Sci. 49, 610–616 (2010).
pubmed: 20858363
pmcid: 2949431
Boldt, L. et al. Toward evidence-based severity assessment in mouse models with repeated seizures: I. Electrical kindling. Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2020.107689 (2021).
doi: 10.1016/j.yebeh.2020.107689
pubmed: 33418481
Reiber, M. et al. Development of behavioral patterns in young C57BL/6J mice: a home cage-based study. Sci. Rep. 12, 2550. https://doi.org/10.1038/s41598-022-06395-1 (2022).
doi: 10.1038/s41598-022-06395-1
pubmed: 35169182
pmcid: 8847349
Shepherd, A. J., Cloud, M. E., Cao, Y. Q. & Mohapatra, D. P. Deficits in Burrowing Behaviors Are Associated With Mouse Models of Neuropathic but Not Inflammatory Pain or Migraine. Front. Behav. Neurosci. 12, 124. https://doi.org/10.3389/fnbeh.2018.00124 (2018).
doi: 10.3389/fnbeh.2018.00124
pubmed: 30002622
pmcid: 6031738
Jirkof, P. et al. Administration of Tramadol or Buprenorphine via the drinking water for post-operative analgesia in a mouse-osteotomy model. Sci. Rep. 9, 10749. https://doi.org/10.1038/s41598-019-47186-5 (2019).
doi: 10.1038/s41598-019-47186-5
pubmed: 31341225
pmcid: 6656891
Talbot, S. R. et al. Defining body-weight reduction as a humane endpoint: a critical appraisal. Lab. Anim. 54, 99–110. https://doi.org/10.1177/0023677219883319 (2020).
doi: 10.1177/0023677219883319
pubmed: 31665969
Roughan, J. V., Bertrand, H. G. & Isles, H. M. Meloxicam prevents COX-2-mediated post-surgical inflammation but not pain following laparotomy in mice. Eur. J. Pain 20, 231–240. https://doi.org/10.1002/ejp.712 (2016).
doi: 10.1002/ejp.712
pubmed: 25908253
Zechner, D. et al. Generalizability, Robustness and Replicability When Evaluating Wellbeing of Laboratory Mice with Various Methods. Animals (Basel) https://doi.org/10.3390/ani12212927 (2022).
doi: 10.3390/ani12212927
pubmed: 36359051
Palme, R. Non-invasive measurement of glucocorticoids: Advances and problems. Physiol. Behav. 199, 229–243. https://doi.org/10.1016/j.physbeh.2018.11.021 (2019).
doi: 10.1016/j.physbeh.2018.11.021
pubmed: 30468744
Iyengar, S., Kim, H. S. & Wood, P. L. μ-, δ-, κ-and ϵ-Opioid receptor modulation of the hypothalamic-pituitary-adrenocortical (HPA) axis: Subchronic tolerance studies of endogenous opioid peptides. Brain Res. 435, 220–226 (1987).
doi: 10.1016/0006-8993(87)91604-0
pubmed: 2892574
Cusack, B. & Buggy, D. J. Anaesthesia, analgesia, and the surgical stress response. BJA Educ. 20, 321–328. https://doi.org/10.1016/j.bjae.2020.04.006 (2020).
doi: 10.1016/j.bjae.2020.04.006
pubmed: 33456967
pmcid: 7807970
Arras, M. et al. Schmerztherapie bei Versuchstieren: Fachinformation aus dem Ausschuss für Anästhesie der GV-SOLAS in Zusammenarbeit mit dem Arbeitskreis 4 in der TVT. Schmerztherapie bei Versuchstieren, (2020).
Ingrao, J. C. et al. Aqueous stability and oral pharmacokinetics of meloxicam and carprofen in male C57BL/6 mice. J. Am. Assoc. Lab. Anim. Sci. 52, 553–559 (2013).
pubmed: 24041210
pmcid: 3784660
Grant, G. J. et al. DRV liposomal bupivacaine: preparation, characterization, and in vivo evaluation in mice. Pharm. Res. 18, 336–343. https://doi.org/10.1023/a:1011059131348 (2001).
doi: 10.1023/a:1011059131348
pubmed: 11442274
Huss, M. K. & Pacharinsak, C. A review of long-acting parenteral analgesics for mice and rats. J. Am. Assoc. Lab. Anim. Sci. 61, 595–602. https://doi.org/10.30802/aalas-jaalas-22-000061 (2022).
doi: 10.30802/aalas-jaalas-22-000061
pubmed: 36379476
pmcid: 9732779
Healy, J. R. et al. Evaluation of an improved sustained-release buprenorphine formulation for use in mice. Am. J. Vet. Res. 75, 619–625. https://doi.org/10.2460/ajvr.75.7.619 (2014).
doi: 10.2460/ajvr.75.7.619
pubmed: 24959727
Percie du Sert, N. et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS. Biol. 18, e3000410. https://doi.org/10.1371/journal.pbio.3000410 (2020).
doi: 10.1371/journal.pbio.3000410
pubmed: 32663219
pmcid: 7360023
Mähler Convenor, M. et al. FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units. Lab. Anim. 48, 178–192. https://doi.org/10.1177/0023677213516312 (2014).
doi: 10.1177/0023677213516312
pubmed: 24496575
R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, Austria, 2022).
Ernst, L. et al. Improvement of the Mouse Grimace Scale set-up for implementing a semi-automated Mouse Grimace Scale scoring (Part 1). Lab. Anim. 54, 83–91. https://doi.org/10.1177/0023677219881655 (2020).
doi: 10.1177/0023677219881655
pubmed: 31648592
Ernst, L. et al. Semi-automated generation of pictures for the Mouse Grimace Scale: A multi-laboratory analysis (Part 2). Lab. Anim. 54, 92–98. https://doi.org/10.1177/0023677219881664 (2020).
doi: 10.1177/0023677219881664
pubmed: 31660777
R package 'corrplot': Visualization of a Correlation Matrix v. Version 0.92 (2021).
ggplot2: Elegant Graphics for Data Analysis (Springer-Verlag New York, 2016).