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Comparison of Burrowing and Stimuli-Evoked Pain Behaviors as End-Points in Rat Models of Inflammatory Pain and Peripheral Neuropathic Pain.

Muralidharan A, Kuo A, Jacob M, Lourdesamy JS, Carvalho LM, Nicholson JR, Corradini L, Smith MT - Front Behav Neurosci (2016)

Bottom Line: For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws.By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability.However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrated Preclinical Drug Development, The University of Queensland Brisbane, QLD, Australia.

ABSTRACT
Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤ 450 g of gravel on any 2 days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund's complete adjuvant (FCA) or saline, or underwent unilateral chronic constriction injury (CCI) of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA-and CCI- rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

No MeSH data available.


Related in: MedlinePlus

Experimental design and chronological order of experimental procedures and/or behavioral testing used in the rat models of (A) FCA-induced inflammatory pain and (B) CCI of the sciatic nerve model of neuropathic pain. PV, paw volume; PPT, Paw Pressure Threshold; VF, von Frey.
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Figure 1: Experimental design and chronological order of experimental procedures and/or behavioral testing used in the rat models of (A) FCA-induced inflammatory pain and (B) CCI of the sciatic nerve model of neuropathic pain. PV, paw volume; PPT, Paw Pressure Threshold; VF, von Frey.

Mentions: The timelines for assessments of burrowing behavior, mechanical hyperalgesia, hindpaw edema and/or mechanical allodynia in the FCA- and CCI-rat models used in the present study, are summarized in Figures 1A,B, respectively. The number of rats used per cohort and the number of animals excluded because they did not meet the burrowing criterion, are shown in Table 1. The general animal health (body weights), pain hypersensitivity behaviors (mechanical allodynia and mechanical hyperalgesia for CCI- and FCA-rats respectively), hindpaw volumes (FCA-rats only) and burrowing data from all rat cohorts are described in the following sections.


Comparison of Burrowing and Stimuli-Evoked Pain Behaviors as End-Points in Rat Models of Inflammatory Pain and Peripheral Neuropathic Pain.

Muralidharan A, Kuo A, Jacob M, Lourdesamy JS, Carvalho LM, Nicholson JR, Corradini L, Smith MT - Front Behav Neurosci (2016)

Experimental design and chronological order of experimental procedures and/or behavioral testing used in the rat models of (A) FCA-induced inflammatory pain and (B) CCI of the sciatic nerve model of neuropathic pain. PV, paw volume; PPT, Paw Pressure Threshold; VF, von Frey.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4862327&req=5

Figure 1: Experimental design and chronological order of experimental procedures and/or behavioral testing used in the rat models of (A) FCA-induced inflammatory pain and (B) CCI of the sciatic nerve model of neuropathic pain. PV, paw volume; PPT, Paw Pressure Threshold; VF, von Frey.
Mentions: The timelines for assessments of burrowing behavior, mechanical hyperalgesia, hindpaw edema and/or mechanical allodynia in the FCA- and CCI-rat models used in the present study, are summarized in Figures 1A,B, respectively. The number of rats used per cohort and the number of animals excluded because they did not meet the burrowing criterion, are shown in Table 1. The general animal health (body weights), pain hypersensitivity behaviors (mechanical allodynia and mechanical hyperalgesia for CCI- and FCA-rats respectively), hindpaw volumes (FCA-rats only) and burrowing data from all rat cohorts are described in the following sections.

Bottom Line: For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws.By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability.However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrated Preclinical Drug Development, The University of Queensland Brisbane, QLD, Australia.

ABSTRACT
Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤ 450 g of gravel on any 2 days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund's complete adjuvant (FCA) or saline, or underwent unilateral chronic constriction injury (CCI) of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA-and CCI- rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

No MeSH data available.


Related in: MedlinePlus