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dc.contributor.authorHavelin, Joshua
dc.contributor.authorImbert, Ian
dc.contributor.authorSukhtankar, Devki
dc.contributor.authorRemeniuk, Bethany
dc.contributor.authorPelletier, Ian
dc.contributor.authorGentry, Jonathan
dc.contributor.authorOkun, Alec
dc.contributor.authorTiutan, Timothy
dc.contributor.authorPorreca, Frank
dc.contributor.authorKing, Tamara E.
dc.date.accessioned2017-07-06T22:37:47Z
dc.date.available2017-07-06T22:37:47Z
dc.date.issued2017-05-17
dc.identifier.citationMediation of Movement-Induced Breakthrough Cancer Pain by IB4-Binding Nociceptors in Rats 2017, 37 (20):5111 The Journal of Neuroscienceen
dc.identifier.issn0270-6474
dc.identifier.issn1529-2401
dc.identifier.pmid28438966
dc.identifier.doi10.1523/JNEUROSCI.1212-16.2017
dc.identifier.urihttp://hdl.handle.net/10150/624635
dc.description.abstractCancer-induced bone pain is characterized by moderate to severe ongoing pain that commonly requires the use of opiates. Even when ongoing pain is well controlled, patients can suffer breakthrough pain (BTP), episodic severe pain that "breaks through" the medication. We developed a novel model of cancer-induced BTP using female rats with mammary adenocarcinoma cells sealed within the tibia. We demonstrated previously that rats with bone cancer learn to prefer a context paired with saphenous nerve block to elicit pain relief (i.e., conditioned place preference, CPP), revealing the presence of ongoing pain. Treatment with systemic morphine abolished CPP to saphenous nerve block, demonstrating control of ongoing pain. Here, we show that pairing BTP induced by experimenter-induced movement of the tumor-bearing hindlimb with a context produces conditioned place avoidance (CPA) in rats treated with morphine to control ongoing pain, consistent with clinical observation of BTP. Preventing movement-induced afferent input by saphenous nerve block before, but not after, hindlimb movement blocked movement-induced BTP. Ablation of isolectin B4 (IB4)-binding, but not TRPV1(+), sensory afferents eliminated movement-induced BTP, suggesting that input from IB4-binding fibers mediates BTP. Identification of potential molecular targets specific to this population of fibers may allow for the development of peripherally restricted analgesics that control BTP and improve quality of life in patients with skeletal metastases.
dc.description.sponsorshipNational Institutes of Health (National Cancer Institute) [T32CA009213]; National Institutes on Drug Abuse [DA034975]; National Institute of General Medical Sciences [P20GM103643]en
dc.language.isoenen
dc.publisherSOC NEUROSCIENCEen
dc.relation.urlhttp://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.1212-16.2017en
dc.rightsCopyright © 2017 the authors.en
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectbreakthrough painen
dc.subjectc-fiberen
dc.subjectcancer painen
dc.subjectIB4en
dc.subjectnonpeptidergicen
dc.subjectpeptidergicen
dc.titleMediation of Movement-Induced Breakthrough Cancer Pain by IB4-Binding Nociceptors in Ratsen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Coll Med, Dept Pharmacolen
dc.contributor.departmentUniv Arizona, Arizona Canc Ctr, Dept Canc Biolen
dc.identifier.journalThe Journal of Neuroscienceen
dc.description.note6 month embargo; Published: 17 May 2017.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2017-11-18T00:00:00Z
html.description.abstractCancer-induced bone pain is characterized by moderate to severe ongoing pain that commonly requires the use of opiates. Even when ongoing pain is well controlled, patients can suffer breakthrough pain (BTP), episodic severe pain that "breaks through" the medication. We developed a novel model of cancer-induced BTP using female rats with mammary adenocarcinoma cells sealed within the tibia. We demonstrated previously that rats with bone cancer learn to prefer a context paired with saphenous nerve block to elicit pain relief (i.e., conditioned place preference, CPP), revealing the presence of ongoing pain. Treatment with systemic morphine abolished CPP to saphenous nerve block, demonstrating control of ongoing pain. Here, we show that pairing BTP induced by experimenter-induced movement of the tumor-bearing hindlimb with a context produces conditioned place avoidance (CPA) in rats treated with morphine to control ongoing pain, consistent with clinical observation of BTP. Preventing movement-induced afferent input by saphenous nerve block before, but not after, hindlimb movement blocked movement-induced BTP. Ablation of isolectin B4 (IB4)-binding, but not TRPV1(+), sensory afferents eliminated movement-induced BTP, suggesting that input from IB4-binding fibers mediates BTP. Identification of potential molecular targets specific to this population of fibers may allow for the development of peripherally restricted analgesics that control BTP and improve quality of life in patients with skeletal metastases.


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