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Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain.
Brain Res. 2007 Nov 14; 1180:7-19.BR

Abstract

Pain associated with cancer, particularly when tumors metastasize to bone, is often severe and debilitating. Better understanding of the neurobiological mechanisms underlying cancer pain will likely lead to the development of more effective treatments. The aim of this study was to characterize changes in response properties of nociceptive dorsal horn neurons following implantation of fibrosarcoma cells into and around the calcaneus bone, an established model of cancer pain. Extracellular electrophysiological recordings were made from wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons in mice with tumor-evoked hyperalgesia and control mice. WDR and HT neurons were examined for ongoing activity and responses to mechanical, heat, and cold stimuli applied to the plantar surface of the hind paw. Behavioral experiments showed that mice exhibited hyperalgesia to mechanical and heat stimuli applied to their tumor-bearing hind paw. WDR, but not HT, nociceptive dorsal horn neurons in tumor-bearing mice exhibited sensitization to mechanical, heat, and cold stimuli and may contribute to tumor-evoked hyperalgesia. Specifically, the proportion of WDR neurons that exhibited ongoing activity and their evoked discharge rates were greater in tumor-bearing than in control mice. In addition, WDR neurons exhibited lower response thresholds for mechanical and heat stimuli, and increased responses to suprathreshold mechanical, heat, and cold stimuli. Our findings show that sensitization of WDR neurons contributes to cancer pain and supports the notion that the mechanisms underlying cancer pain differ from those that contribute to inflammatory and neuropathic pain.

Authors+Show Affiliations

Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, 17-252 Moos Tower, 515 Delaware St., S.E., Minneapolis, Minnesota 55455, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17935703

Citation

Khasabov, Sergey G., et al. "Tumor-evoked Hyperalgesia and Sensitization of Nociceptive Dorsal Horn Neurons in a Murine Model of Cancer Pain." Brain Research, vol. 1180, 2007, pp. 7-19.
Khasabov SG, Hamamoto DT, Harding-Rose C, et al. Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain. Brain Res. 2007;1180:7-19.
Khasabov, S. G., Hamamoto, D. T., Harding-Rose, C., & Simone, D. A. (2007). Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain. Brain Research, 1180, 7-19.
Khasabov SG, et al. Tumor-evoked Hyperalgesia and Sensitization of Nociceptive Dorsal Horn Neurons in a Murine Model of Cancer Pain. Brain Res. 2007 Nov 14;1180:7-19. PubMed PMID: 17935703.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain. AU - Khasabov,Sergey G, AU - Hamamoto,Darryl T, AU - Harding-Rose,Catherine, AU - Simone,Donald A, Y1 - 2007/09/14/ PY - 2007/07/12/received PY - 2007/08/20/revised PY - 2007/08/24/accepted PY - 2007/10/16/pubmed PY - 2008/2/6/medline PY - 2007/10/16/entrez SP - 7 EP - 19 JF - Brain research JO - Brain Res VL - 1180 N2 - Pain associated with cancer, particularly when tumors metastasize to bone, is often severe and debilitating. Better understanding of the neurobiological mechanisms underlying cancer pain will likely lead to the development of more effective treatments. The aim of this study was to characterize changes in response properties of nociceptive dorsal horn neurons following implantation of fibrosarcoma cells into and around the calcaneus bone, an established model of cancer pain. Extracellular electrophysiological recordings were made from wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons in mice with tumor-evoked hyperalgesia and control mice. WDR and HT neurons were examined for ongoing activity and responses to mechanical, heat, and cold stimuli applied to the plantar surface of the hind paw. Behavioral experiments showed that mice exhibited hyperalgesia to mechanical and heat stimuli applied to their tumor-bearing hind paw. WDR, but not HT, nociceptive dorsal horn neurons in tumor-bearing mice exhibited sensitization to mechanical, heat, and cold stimuli and may contribute to tumor-evoked hyperalgesia. Specifically, the proportion of WDR neurons that exhibited ongoing activity and their evoked discharge rates were greater in tumor-bearing than in control mice. In addition, WDR neurons exhibited lower response thresholds for mechanical and heat stimuli, and increased responses to suprathreshold mechanical, heat, and cold stimuli. Our findings show that sensitization of WDR neurons contributes to cancer pain and supports the notion that the mechanisms underlying cancer pain differ from those that contribute to inflammatory and neuropathic pain. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/17935703/Tumor_evoked_hyperalgesia_and_sensitization_of_nociceptive_dorsal_horn_neurons_in_a_murine_model_of_cancer_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(07)02078-1 DB - PRIME DP - Unbound Medicine ER -