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Functional interactions between tumor and peripheral nerve: morphology, algogen identification, and behavioral characterization of a new murine model of cancer pain.
J Neurosci. 2001 Dec 01; 21(23):9355-66.JN

Abstract

This paper describes a model of tumor-induced bone destruction and hyperalgesia produced by implantation of fibrosarcoma cells into the mouse calcaneus bone. Histological examination indicates that tumor cells adhere to the bone edge as early as post-implantation day (PID) 3, but osteolysis does not begin until PID 6, correlating with the development of hyperalgesia. C3H/He mice exhibit a reproducible hyperalgesia to mechanical and cold stimuli between PID 6 and 16. These behaviors are present but significantly reduced with subcutaneous implantation that does not involve bone. Systemic administration of morphine (ED(50) 9.0 mg/kg) dose-dependently attenuated the mechanical hyperalgesia. In contrast, bone destruction and hypersensitivity were not evident in mice implanted with melanoma tumors or a paraffin mass of similar size. A novel microperfusion technique was used to identify elevated levels of the putative algogen endothelin (ET) in perfusates collected from the tumor sites of hyperalgesic mice between PID 7 and 12. Increased ET was evident in microperfusates from fibrosarcoma tumor-implanted mice but not from melanoma tumor-implanted mice, which are not hyperalgesic. Intraplantar injection of ET-1 in naive and, to a greater extent, fibrosarcoma tumor-bearing mice produced spontaneous pain behaviors, suggesting that ET-1 activates primary afferent fibers. Intraplantar but not systemic injection of the ET-A receptor antagonist BQ-123 partially blocked tumor-associated mechanical hyperalgesia, indicating that ET-1 contributes to tumor-induced nociception. This model provides a unique approach for quantifying the behavioral, biochemical, and electrophysiological consequences of tumor-nerve interactions.

Authors+Show Affiliations

Departments of Pharmacology, University of Minnesota Schools of Medicine and Veterinary Medicine, Minneapolis, Minnesota 55455, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11717369

Citation

Wacnik, P W., et al. "Functional Interactions Between Tumor and Peripheral Nerve: Morphology, Algogen Identification, and Behavioral Characterization of a New Murine Model of Cancer Pain." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 21, no. 23, 2001, pp. 9355-66.
Wacnik PW, Eikmeier LJ, Ruggles TR, et al. Functional interactions between tumor and peripheral nerve: morphology, algogen identification, and behavioral characterization of a new murine model of cancer pain. J Neurosci. 2001;21(23):9355-66.
Wacnik, P. W., Eikmeier, L. J., Ruggles, T. R., Ramnaraine, M. L., Walcheck, B. K., Beitz, A. J., & Wilcox, G. L. (2001). Functional interactions between tumor and peripheral nerve: morphology, algogen identification, and behavioral characterization of a new murine model of cancer pain. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 21(23), 9355-66.
Wacnik PW, et al. Functional Interactions Between Tumor and Peripheral Nerve: Morphology, Algogen Identification, and Behavioral Characterization of a New Murine Model of Cancer Pain. J Neurosci. 2001 Dec 1;21(23):9355-66. PubMed PMID: 11717369.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional interactions between tumor and peripheral nerve: morphology, algogen identification, and behavioral characterization of a new murine model of cancer pain. AU - Wacnik,P W, AU - Eikmeier,L J, AU - Ruggles,T R, AU - Ramnaraine,M L, AU - Walcheck,B K, AU - Beitz,A J, AU - Wilcox,G L, PY - 2001/11/22/pubmed PY - 2002/1/12/medline PY - 2001/11/22/entrez SP - 9355 EP - 66 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 21 IS - 23 N2 - This paper describes a model of tumor-induced bone destruction and hyperalgesia produced by implantation of fibrosarcoma cells into the mouse calcaneus bone. Histological examination indicates that tumor cells adhere to the bone edge as early as post-implantation day (PID) 3, but osteolysis does not begin until PID 6, correlating with the development of hyperalgesia. C3H/He mice exhibit a reproducible hyperalgesia to mechanical and cold stimuli between PID 6 and 16. These behaviors are present but significantly reduced with subcutaneous implantation that does not involve bone. Systemic administration of morphine (ED(50) 9.0 mg/kg) dose-dependently attenuated the mechanical hyperalgesia. In contrast, bone destruction and hypersensitivity were not evident in mice implanted with melanoma tumors or a paraffin mass of similar size. A novel microperfusion technique was used to identify elevated levels of the putative algogen endothelin (ET) in perfusates collected from the tumor sites of hyperalgesic mice between PID 7 and 12. Increased ET was evident in microperfusates from fibrosarcoma tumor-implanted mice but not from melanoma tumor-implanted mice, which are not hyperalgesic. Intraplantar injection of ET-1 in naive and, to a greater extent, fibrosarcoma tumor-bearing mice produced spontaneous pain behaviors, suggesting that ET-1 activates primary afferent fibers. Intraplantar but not systemic injection of the ET-A receptor antagonist BQ-123 partially blocked tumor-associated mechanical hyperalgesia, indicating that ET-1 contributes to tumor-induced nociception. This model provides a unique approach for quantifying the behavioral, biochemical, and electrophysiological consequences of tumor-nerve interactions. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/11717369/Functional_interactions_between_tumor_and_peripheral_nerve:_morphology_algogen_identification_and_behavioral_characterization_of_a_new_murine_model_of_cancer_pain_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=11717369 DB - PRIME DP - Unbound Medicine ER -