Scientists who perform major survival surgery on laboratory animals face a dual welfare
and methodological challenge: how to choose surgical anesthetics and post-operative analgesics
that will best control animal suffering, knowing that both pain and the drugs that manage
pain can all affect research outcomes. Scientists who publish full descriptions of animal
procedures allow critical and systematic reviews of data, demonstrate their adherence to
animal welfare norms, and guide other scientists on how to conduct their own studies in the
field. We investigated what information on animal pain management a reasonably diligent
scientist might find in planning for a successful experiment. To explore how scientists in a
range of fields describe their management of this ethical and methodological concern, we
scored 400 scientific articles that included major animal survival surgeries as part of their
experimental methods, for the completeness of information on anesthesia and analgesia.
The 400 articles (250 accepted for publication pre-2011, and 150 in 2014–15, along with
174 articles they reference) included thoracotomies, craniotomies, gonadectomies, organ
transplants, peripheral nerve injuries, spinal laminectomies and orthopedic procedures in
dogs, primates, swine, mice, rats and other rodents. We scored articles for Publication
Completeness (PC), which was any mention of use of anesthetics or analgesics; Analgesia
Use (AU) which was any use of post-surgical analgesics, and Analgesia Completeness (a
composite score comprising intra-operative analgesia, extended post-surgical analgesia,
and use of multimodal analgesia). 338 of 400 articles were PC. 98 of these 338 were AU,
with some mention of analgesia, while 240 of 338 mentioned anesthesia only but not postsurgical
analgesia. Journals’ caliber, as measured by their 2013 Impact Factor, had no
effect on PC or AU. We found no effect of whether a journal instructs authors to consult the
ARRIVE publishing guidelines published in 2010 on PC or AC for the 150 mouse and rat
articles in our 2014–15 dataset. None of the 302 articles that were silent about analgesic
use included an explicit statement that analgesics were withheld, or a discussion of how
pain management or untreated pain might affect results. We conclude that current scientific
literature cannot be trusted to present full detail on use of animal anesthetics and analgesics.
We report that publication guidelines focus more on other potential sources of bias in
experimental results, under-appreciate the potential for pain and pain drugs to skew data,
PLOS ONE | DOI:10.1371/journal.pone.0155001 May 12, 2016 1 / 24
a11111
OPEN ACCESS
Citation: Carbone L, Austin J (2016) Pain and
Laboratory Animals: Publication Practices for Better
Data Reproducibility and Better Animal Welfare.
PLoS ONE 11(5): e0155001. doi:10.1371/journal.
pone.0155001
Editor: Chang-Qing Gao, Central South University,
CHINA
Received: December 29, 2015
Accepted: April 22, 2016
Published: May 12, 2016
Copyright: © 2016 Carbone, Austin. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
Data Availability Statement: All relevant data are
within the paper and its Supporting Information files.
Authors may be contacted for further information.
Funding: This study was funded by the United
States National Science Foundation Division of Social
and Economic Sciences. Award #1455838. The
funder had no role in study design, data collection
and analysis, decision to publish, or preparation of
the manuscript.
Competing Interests: The authors have declared
that no competing interests exist.
and thus mostly treat pain management as solely an animal welfare concern, in the jurisdiction
of animal care and use committees. At the same time, animal welfare regulations do not
include guidance on publishing animal data, even though publication is an integral part of
the cycle of research and can affect the welfare of animals in studies building on published
work, leaving it to journals and authors to voluntarily decide what details of animal use to
publish. We suggest that journals, scientists and animal welfare regulators should revise
current guidelines and regulations, on treatment of pain and on transparent reporting of
treatment of pain, to improve this dual welfare and data-quality deficiency.
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Evaluation of Candidates for Systemic Analgesia and General Anesthesia in the Emerging Model Cephalopod, Euprymna berryi
Cephalopods’ remarkable behavior and complex neurobiology make them valuable comparative model organisms, but studies aimed at enhancing welfare of captive cephalopods remain uncommon. Increasing regulation of cephalopods in research laboratories has resulted in growing interest in welfare-oriented refinements, including analgesia and anesthesia. Although general and local anesthesia in cephalopods have received limited prior study, there have been no studies of systemic analgesics in cephalopods to date. Here we show that analgesics from several different drug classes may be effective in E. berryi. Buprenorphine, ketorolac and dexmedetomidine, at doses similar to those used in fish, showed promising effects on baseline nociceptive thresholds, excitability of peripheral sensory nerves, and on behavioral responses to transient noxious stimulation. We found no evidence of positive effects of acetaminophen or ketamine administered at doses that are effective in vertebrates. Bioinformatic analyses suggested conserved candidate receptors for dexmedetomidine and ketorolac, but not buprenorphine. We also show that rapid general immersion anesthesia using a mix of MgCl2 and ethanol was successful in E. berryi at multiple age classes, similar to findings in other cephalopods. These data indicate that systemic analgesia and general anesthesia in Euprymna berryi are achievable welfare enhancing interventions, but further study and refinement is warranted.
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- NSF-PAR ID:
- 10405325
- Date Published:
- Journal Name:
- Biology
- Volume:
- 12
- Issue:
- 2
- ISSN:
- 2079-7737
- Page Range / eLocation ID:
- 201
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/biology12020201
