Painful dilemmas: the ethics of animal-based pain research

Magalhães-Sant’Ana, Manuel; Sandøe, Peter; Olsson, I. Anna S.

doi:10.1017/s0962728600000063

Cited by 24 publications

(2 citation statements)

References 95 publications

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“…This assessment of mechanical pain threshold provides better translation to surgical pain than alternative pain assessment techniques because this method of evoking pain more closely mimics postoperative nociception as compared with thermal or chemical sensitivity, which elicit pain through exposure of the peripheral sensory nerves. 21,24 The positive analgesic effects in the paw withdrawal study prompted the progression to examining the clinical efficacy of LHC-Bup.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Efficacy of a Long-lasting, Highly Concentrated Buprenorphine Solution in Rats

Houston

Tan

Thomas

et al. 2021

j am assoc lab anim sci

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Buprenorphine (Bup) is an opioid analgesic that is commonly used in laboratory rodents to provide postoperative analgesia. However, dosing every 4 to 6 h is necessary to maintain an analgesic plasma concentration of the drug. A long lasting, highly concentrated veterinary formulation of Bup (LHC-Bup) has been used to provide prolonged analgesia in cats and nonhuman primates. In the current study, we evaluated the duration of efficacy of LHC-Bup to determine if this formulation would provide a similarly prolonged analgesia in rats. Drug concentrations were measured after subcutaneous injection of 0.5 mg/kg LHC-Bup in both male and female rats. Plasma levels were measured at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, and 72 h. Male and female rats had peak plasma levels of LHC-Bup at 90 ng/mL and 34 ng/mL, respectively, at 15 min after administration, with a steady decrease by 24 h to 0.7 ng/mL in males and 1.3 ng/mL in females. Mechanical pain tolerance was evaluated after LHC-Bup administration using a Randall-Selitto analgesiometer to assess paw withdrawal. Male rats had a significantly longer paw withdrawal time for up to 12 h after administration, and females had longer paw withdrawal times for up to 24 h. An experimental laparotomy model was then used to assess the clinical efficacy of LHC-Bup at 0.5 mg/kg. LHC-Bup treatment was associated with a greater total distance traveled, reduced time to retrieve a food treat, and reduced grooming from 3 to 12 h after surgery as compared with saline controls. Groups receiving LHC-Bup showed coprophagy whereas other rats did not. These results suggest that administering LHC-Bup at 0.5 mg/kg provides therapeutic plasma concentrations for 12 to 24 h after administration and analgesic efficacy for at least 12 h after dosing. As such, LHC-Bup is a suitable alternative to Bup-HCl.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Efficacy of a Long-lasting, Highly Concentrated Buprenorphine Solution in Rats

Houston

Tan

Thomas

et al. 2021

j am assoc lab anim sci

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“…For this task, rodents are widely used. However, research with these models often involves invasive procedures or requires the use of anesthetics, which may introduce biases by directly or indirectly altering the physiological processes into play ( Magalhães-Sant’Ana et al . 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Distinct clusters of human pain gene orthologs in Caenorhabditis elegans regulate thermo-nociceptive sensitivity and plasticity

Jordan

Glauser

2023

Genetics

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The detection and avoidance of harmful stimuli are essential animal capabilities. The molecular and cellular mechanisms controlling nociception and its plasticity are conserved, genetically-controlled processes of broad biomedical interest given their relevance to understand and treat pain conditions that represent a major health burden. Recent genome-wide association studies (GWAS) have identified a rich set of polymorphisms related to different pain conditions and pointed to many human pain gene candidates, whose connection to the pain pathways is however often poorly understood. Here, we used a computer-assisted C. elegans thermal avoidance analysis pipeline to screen for behavioral defects in a set of 109 mutants for genes orthologous to human pain-related genes. We measured heat-evoked reversal thermo-sensitivity profiles, as well as spontaneous reversal rate, and compared naïve animals with adapted animals submitted to a series of repeated noxious heat stimuli, which in wild type causes a progressive habituation. Mutations affecting 28 genes displayed defects in at least one of the considered parameters, and could be clustered based on specific phenotypic footprints, such as high-sensitivity mutants, non-adapting mutants or mutants combining multiple defects. Collectively, our data reveal the functional architecture of a network of conserved pain-related genes in C. elegans and offer novel entry points for the characterization of poorly understood human pain genes in this genetic model.

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Veterinary Ethics and the Use of Animals in Research

Gilbert¹,

Wolfensohn²

2012

Veterinary &Amp; Animal Ethics

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Painful dilemmas: the ethics of animal-based pain research

Cited by 24 publications

References 95 publications

Pharmacokinetics and Efficacy of a Long-lasting, Highly Concentrated Buprenorphine Solution in Rats

Pharmacokinetics and Efficacy of a Long-lasting, Highly Concentrated Buprenorphine Solution in Rats

Distinct clusters of human pain gene orthologs in Caenorhabditis elegans regulate thermo-nociceptive sensitivity and plasticity

Veterinary Ethics and the Use of Animals in Research

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