Measurement of CFA-Induced Hyperalgesia and Morphine-Induced Analgesia in Rats: Dorsal vs Plantar Mechanical Stimulation of the Hindpaw

Soignier, R. Denis; Taylor, Bradley K.; Baiamonte, Brandon A.; Lee, Frank A.; Paúl, Dennis; Gould, Harry J.

doi:10.1111/j.1526-4637.2011.01066.x

Cited by 13 publications

(18 citation statements)

References 27 publications

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“…Consistent with our primary observation of distinct differences in neuropathic versus inflammatory pathophysiology between sub‐strains, is a report of strain‐related differences in sensitivity to spared nerve injury, linked to spinal cord and midbrain serotonin levels, which were largely absent in CFA‐inflamed mice (Wijnvoord et al., ). Our CFA‐induced hyperalgesia was reversed dose‐dependently by morphine in all SD sub‐strains, in general agreement with other studies (Wang et al., ; Soignier et al., ). In contrast to our CCI results, we found a subtle difference in morphine‐induced anti‐nociception between sub‐strains.…”

Section: Discussionsupporting

confidence: 93%

Vendor‐derived differences in injury‐induced pain phenotype and pharmacology of Sprague–Dawley rats: Does it matter?

Kristensen

Heegaard

Hestehave

et al. 2016

European Journal of Pain

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Section: Discussionsupporting

confidence: 93%

Vendor‐derived differences in injury‐induced pain phenotype and pharmacology of Sprague–Dawley rats: Does it matter?

Kristensen

Heegaard

Hestehave

et al. 2016

European Journal of Pain

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“…Thus, we were surprised that Crl:SD rats were paradoxically least sensitive to Randall Selitto stimulation of the hindpaw (Crl:SD<Hsd:SD<LEW<WKY=F344). Thereafter, following CFA‐injection, with the threshold difference considered as an index of mechanical hyperalgesia (Kristensen et al., ; Soignier et al., ), we observed similar responses in all strains, with the exception of WKY which developed only a modest hyperalgesia. These findings were unexpected based on (a) reports that F344 rats develop more robust hyperalgesia than LEW rats in response to acute inflammation induced by CFA (Zhang, Lao, Qiao, & Ruda, ), carrageenan (Fecho, Manning, Maixner, & Schmitt, ; Fecho & Valtschanoff, ; Juif, Anton, & Hanesch, ) or formalin (Lariviere, Sattar, & Melzack, ) (b) increased expression of formalin‐induced second phase nocifensive behaviours in WKY versus SD rats (Burke et al., ) (c) the comparable level of CFA‐induced oedema in WKY and the other strains in this study.…”

Section: Discussionsupporting

confidence: 69%

The analgesic efficacy of morphine varies with rat strain and experimental pain model: implications for target validation efforts in pain drug discovery

Hestehave

Abelson

Pedersen

et al. 2018

European Journal of Pain

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Background Translating efficacy of analgesic drugs from animal models to humans remains challenging. Reasons are multifaceted, but lack of sufficiently rigorous preclinical study design criteria and phenotypically relevant models may be partly responsible. To begin to address this fundamental issue, we assessed the analgesic efficacy of morphine in three inbred rat strains (selected based on stress reactivity and affective/pain phenotypes), and outbred Sprague Dawley ( SD ) rats supplied from two vendors. Methods Sensitivity to morphine (0.3–6.0 mg/kg, s.c.) was evaluated in the hot plate test of acute thermal nociception, the Complete Freund's Adjuvant ( CFA ) model of inflammatory‐induced mechanical hyperalgesia, and in a locomotor motility assay in male rats from the following strains; Lewis ( LEW ), Fischer (F344), Wistar Kyoto ( WKY ), and SD 's from Envigo and Charles River. Results F344 and SD rats were similarly sensitive to morphine in hot plate and CFA ‐induced inflammatory hyperalgesia (Minimum Effective Dose ( MED ) = 3.0 mg/kg). WKY rats developed a less robust mechanical hypersensitivity after CFA injection, and were less sensitive to morphine in both pain tests ( MED = 6.0 mg/kg). LEW rats were completely insensitive to morphine in the hot plate test, in contrast to the reversal of CFA ‐induced hyperalgesia ( MED = 3.0 mg/kg). All strains exhibited a dose‐dependent reduction in locomotor activity at 3.0–6.0 mg/kg. Conclusion Sensory phenotyping in response to acute thermal and inflammatory‐induced pain, and sensitivity to morphine in various inbred and outbred rat strains indicates that different pathophysiological mechanisms are engaged after injury. This could have profound implications for translating preclinical drug discovery efforts into pain patients. Significance The choice of rat strain used in preclinical pain research can profoundly affect the outcome of experiments in relation to (a) nociceptive threshold responses, and (b) efficacy to analgesic treatment, in assays of acute and tonic inflammatory nociceptive pain.

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“…These anti‐hyperalgesic effects were not due to general behavioural inhibition because within the dose ranges studied, all three drugs do not alter the general locomotor activity (Thorn et al ., ). Similarly, morphine also dose‐dependently attenuated the mechanical and thermal hyperalgesia (Figure ), consistent with the literature (Nagakura et al ., ; Soignier et al ., ). Von Frey filament stimulation does not induce physiological nociception in rats, although a reflexive paw withdrawal can usually be provoked when a large enough pressure is applied to the paw.…”

Section: Discussionmentioning

confidence: 97%

Antihyperalgesic effects of imidazoline I₂ receptor ligands in rat models of inflammatory and neuropathic pain

Thorn

Qiu

et al. 2014

British J Pharmacology

103

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A new imidazoline I2 receptor ligand, CR4056, is effective for chronic inflammatory pain and diabetic neuropathy. However, it is unclear whether other I2 receptor ligands have similar effects and whether antinociceptive tolerance develops with repeated treatment. EXPERIMENTAL APPROACHThe Von Frey filament test was used to measure mechanical hyperalgesia and the plantar test to measure thermal hyperalgesia in rats injected with complete Freund's adjuvant (CFA) treatment or had undergone surgery to induce chronic constriction injury (CCI), models of inflammatory pain and peripheral neuropathic pain respectively. The effects of morphine and I2 receptor ligands, 2-BFI, BU224, tracizoline and CR4056, 3.2-32 mg·kg −1 , i.p., on hyperalgesia or affective pain (as measured by a place escape/avoidance paradigm) were studied in separate experiments. KEY RESULTSMorphine and the I2 receptor ligands (2-BFI, BU224 and tracizoline) all dose-dependently attenuated mechanical and thermal hyperalgesia in CFA-treated rats. The anti-hyperalgesic effects of 2-BFI in CFA-treated and CCI rats were attenuated by the I2 receptor antagonist idazoxan. The combination of 2-BFI and morphine produced additive effects against mechanical hyperalgesia in CFA-treated rats. Repeated treatment (daily for 7-9 days) with 2-BFI or CR4056 did not produce antinociceptive tolerance in CFA-treated or CCI rats. Morphine and the I2 receptor ligands (2-BFI, BU224 and CR4056) were all effective at attenuating place escape/avoidance behaviour in CFA-treated rats. CONCLUSIONS AND IMPLICATIONSImidazoline I2 receptor ligands have antihyperalgesic effects in rat models of inflammatory and neuropathic pain and may represent a new class of pharmacotherapeutics for the management of chronic pain. Abbreviations

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Measurement of CFA-Induced Hyperalgesia and Morphine-Induced Analgesia in Rats: Dorsal vs Plantar Mechanical Stimulation of the Hindpaw

Abstract: Reliable and sensitive assessment of animal pain behaviors is critical to translational pain research. This study demonstrates the importance of using proper test protocols in animal studies and its implication in preclinical screening of potential analgesics.

Cited by 13 publications

References 27 publications

Vendor‐derived differences in injury‐induced pain phenotype and pharmacology of Sprague–Dawley rats: Does it matter?

Vendor‐derived differences in injury‐induced pain phenotype and pharmacology of Sprague–Dawley rats: Does it matter?

The analgesic efficacy of morphine varies with rat strain and experimental pain model: implications for target validation efforts in pain drug discovery

Antihyperalgesic effects of imidazoline I₂ receptor ligands in rat models of inflammatory and neuropathic pain

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Measurement of CFA-Induced Hyperalgesia and Morphine-Induced Analgesia in Rats: Dorsal vs Plantar Mechanical Stimulation of the Hindpaw

Abstract: Reliable and sensitive assessment of animal pain behaviors is critical to translational pain research. This study demonstrates the importance of using proper test protocols in animal studies and its implication in preclinical screening of potential analgesics.

Cited by 13 publications

References 27 publications

Vendor‐derived differences in injury‐induced pain phenotype and pharmacology of Sprague–Dawley rats: Does it matter?

Vendor‐derived differences in injury‐induced pain phenotype and pharmacology of Sprague–Dawley rats: Does it matter?

The analgesic efficacy of morphine varies with rat strain and experimental pain model: implications for target validation efforts in pain drug discovery

Antihyperalgesic effects of imidazoline I2 receptor ligands in rat models of inflammatory and neuropathic pain

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Antihyperalgesic effects of imidazoline I₂ receptor ligands in rat models of inflammatory and neuropathic pain