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A method to enhance the magnitude of tactile hypersensitivity following spinal nerve ligation in rats.
J Neurosci Methods. 2014 Aug 15; 233:50-3.JN

Abstract

BACKGROUND

The rat L5/L6 spinal nerve ligation model (SNL) has been widely used to investigate putative analgesics. Pursuit of novel therapies in preclinical settings requires models with consistent and reproducible phenotypes.

NEW METHOD

We assessed the effects of repetitive stimulation of the hindpaws of SNL and Sham surgery rats during the 2 weeks immediately after surgery on the overall rate of achieving tactile hypersensitivity, as well as the magnitude of the hypersensitivity compared to unprimed rats. Beginning on day 2 post-surgery, and continuing on alternate days for a total of seven sessions, animals underwent light brushing/tapping (termed priming) of the hindpaws ipsilateral and contralateral to surgery.

RESULTS

Priming the ipsilateral hindpaw enhanced the magnitude of tactile hypersensitivity such that the baseline withdrawal threshold (BWT) for primed SNL animals was significantly lower than unprimed SNL animals over post-surgical days 15-29. BWT was not different between primed and unprimed Sham rats. The percentage of SNL primed animals meeting the a priori criterion for tactile hypersensitivity of paw withdrawal threshold less than 2.0 grams was 98.9%±1.1%.

COMPARISON WITH EXISTING METHOD

SNL rats that did not receive stimulation (unprimed) showed significantly higher baseline hypersensitivity when evaluated on days 15-29, exemplified by only 34.5%±7.2% meeting the established <2.0g criterion.

CONCLUSION

Our data indicate that tactile priming during the 2 weeks immediately after SNL surgery enhances the magnitude of tactile hypersensitivity in the SNL model, and provide an optimized assay for evaluating putative analgesics.

Authors+Show Affiliations

Neuroscience Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: simmons-rma@lilly.com.Neuroscience Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: forster_beth_marie@lilly.com.Neuroscience Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: guo_wenhong@lilly.com.Neuroscience Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: knopp_kelly_l@lilly.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24928434

Citation

Simmons, Rosa Maria A., et al. "A Method to Enhance the Magnitude of Tactile Hypersensitivity Following Spinal Nerve Ligation in Rats." Journal of Neuroscience Methods, vol. 233, 2014, pp. 50-3.
Simmons RM, Forster B, Guo W, et al. A method to enhance the magnitude of tactile hypersensitivity following spinal nerve ligation in rats. J Neurosci Methods. 2014;233:50-3.
Simmons, R. M., Forster, B., Guo, W., & Knopp, K. L. (2014). A method to enhance the magnitude of tactile hypersensitivity following spinal nerve ligation in rats. Journal of Neuroscience Methods, 233, 50-3. https://doi.org/10.1016/j.jneumeth.2014.06.001
Simmons RM, et al. A Method to Enhance the Magnitude of Tactile Hypersensitivity Following Spinal Nerve Ligation in Rats. J Neurosci Methods. 2014 Aug 15;233:50-3. PubMed PMID: 24928434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A method to enhance the magnitude of tactile hypersensitivity following spinal nerve ligation in rats. AU - Simmons,Rosa Maria A, AU - Forster,Beth, AU - Guo,Wenhong, AU - Knopp,Kelly L, Y1 - 2014/06/10/ PY - 2013/12/04/received PY - 2014/05/30/revised PY - 2014/06/03/accepted PY - 2014/6/15/entrez PY - 2014/6/15/pubmed PY - 2015/3/31/medline KW - Behavioral test KW - Gabapentin KW - Priming KW - Spinal nerve ligation KW - Tactile hypersensitivity SP - 50 EP - 3 JF - Journal of neuroscience methods JO - J Neurosci Methods VL - 233 N2 - BACKGROUND: The rat L5/L6 spinal nerve ligation model (SNL) has been widely used to investigate putative analgesics. Pursuit of novel therapies in preclinical settings requires models with consistent and reproducible phenotypes. NEW METHOD: We assessed the effects of repetitive stimulation of the hindpaws of SNL and Sham surgery rats during the 2 weeks immediately after surgery on the overall rate of achieving tactile hypersensitivity, as well as the magnitude of the hypersensitivity compared to unprimed rats. Beginning on day 2 post-surgery, and continuing on alternate days for a total of seven sessions, animals underwent light brushing/tapping (termed priming) of the hindpaws ipsilateral and contralateral to surgery. RESULTS: Priming the ipsilateral hindpaw enhanced the magnitude of tactile hypersensitivity such that the baseline withdrawal threshold (BWT) for primed SNL animals was significantly lower than unprimed SNL animals over post-surgical days 15-29. BWT was not different between primed and unprimed Sham rats. The percentage of SNL primed animals meeting the a priori criterion for tactile hypersensitivity of paw withdrawal threshold less than 2.0 grams was 98.9%±1.1%. COMPARISON WITH EXISTING METHOD: SNL rats that did not receive stimulation (unprimed) showed significantly higher baseline hypersensitivity when evaluated on days 15-29, exemplified by only 34.5%±7.2% meeting the established <2.0g criterion. CONCLUSION: Our data indicate that tactile priming during the 2 weeks immediately after SNL surgery enhances the magnitude of tactile hypersensitivity in the SNL model, and provide an optimized assay for evaluating putative analgesics. SN - 1872-678X UR - https://www.unboundmedicine.com/medline/citation/24928434/A_method_to_enhance_the_magnitude_of_tactile_hypersensitivity_following_spinal_nerve_ligation_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-0270(14)00207-6 DB - PRIME DP - Unbound Medicine ER -