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Response to Protocol Review Scenario: Request for more information

Lab Animal volume 45, pages 13–14 (2016)Cite this article

The IACUC reviewer asks a good question, but we do not feel that the contralateral leg would serve as a good control. Rats receiving surgery on both hind legs would ambulate differently from rats undergoing unilateral ligation or unilateral sham surgery, since the former would not have the option of compensating with an unaffected hind leg. This could interfere with the assessment of pain responses. Previous research indicates that “unilateral constriction of the left common sciatic nerve...gives rise to a marked increase in sensitivity to normally innocuous tactile stimuli in both the nerve-injured as well as the intact contralateral hind paws. Although less in magnitude and duration, surgery alone without nerve constriction also produces a decrease in withdrawal threshold of each of the hind paws”1. Accordingly, this study “demonstrated that the contralateral hind paw and either hind paw in sham-operated rats are inappropriate as 'controls'.”

Additionally, it is unclear which parameters Foxworthy will be monitoring to assess whether the drug treatment is effective. Will he use behavioral, biochemical or other tests? For example, if measuring serum cortisol levels as an indicator of effectiveness, Foxworthy would not be able to distinguish between the drug's effectiveness after nerve constriction and its effectiveness after sham surgery if both legs are on the same animal. If, during publication, reviewers should deem that sham surgery on the contralateral leg is not a scientifically valid control treatment, the experiment might need to be repeated using new and separate groups of rats for nerve constriction and sham surgeries, which would relegate the original group of rats to wasted animals.

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References

  1. Pitcher, G.M., Ritchie, J. & Henry, J.L. Nerve constriction in the rat: model of neuropathic, surgical and central pain. Pain, 83, 37–46 (1999).

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  2. Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals 8th edn. (National Academies Press, Washington, DC, 2011).

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Authors and Affiliations

  1. Bailey is the Director of Comparative Medicine, Attending Veterinarian and Adjunct Professor of Physiology and Loh is a Clinical Veterinarian at the National University of Singapore, Singapore.,

    Michele M. Bailey &  Michelle Loh

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  1. Michele M. Bailey
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  2. Michelle Loh
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Bailey, M., Loh, M. Response to Protocol Review Scenario: Request for more information. Lab Anim 45, 13–14 (2016). https://doi.org/10.1038/laban.903

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