Analgesic Efficacy of Bradykinin B1 Antagonists in a Murine Bone Cancer Pain Model

Sevcik, Molly A.; Ghilardi, Joseph R.; Halvorson, Kyle G.; Lindsay, Theodore H.; Kubota, Kazufumi; Mantyh, Patrick W.

doi:10.1016/j.jpain.2005.06.010

Cited by 46 publications

(24 citation statements)

References 16 publications

(15 reference statements)

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“…It has been demonstrated that both bone cancer-induced ongoing and movement-evoked nocifensive behaviors were reduced after the pharmacologic blockade of the B 1 receptor. 113 We have also shown that administration of B 1 antagonists not only reduces bone cancer-induced, pain-related behaviors but that this efficacy is retained in advanced bone cancer pain ( Table 2). 113 One important concept that has emerged over the past decade is that in addition to nerve growth factor (NGF) being able to directly activate sensory neurons that express the trkA receptor, NGF modulates expression and function of a wide variety of molecules and proteins expressed by sensory neurons that express the trkA or p75 receptor.…”

Section: Tumor-derived Products In Generation Of Bone Cancer Painmentioning

confidence: 84%

“…113 We have also shown that administration of B 1 antagonists not only reduces bone cancer-induced, pain-related behaviors but that this efficacy is retained in advanced bone cancer pain ( Table 2). 113 One important concept that has emerged over the past decade is that in addition to nerve growth factor (NGF) being able to directly activate sensory neurons that express the trkA receptor, NGF modulates expression and function of a wide variety of molecules and proteins expressed by sensory neurons that express the trkA or p75 receptor. Some of these molecules and proteins include: neurotransmitters (substance P and CGRP), receptors (bradykinin), channels (P2X3, TRPV1, ASIC-3 and sodium channels), transcription factors (ATF-3), and structural molecules (neurofilaments and the sodium channel anchoring molecule p11).…”

Section: Tumor-derived Products In Generation Of Bone Cancer Painmentioning

confidence: 84%

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Similarities and Differences in Tumor Growth, Skeletal Remodeling and Pain in an Osteolytic and Osteoblastic Model of Bone Cancer

Halvorson

Sevcik

Ghilardi³

et al. 2006

The Clinical Journal of Pain

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More than 1.3 million cases of cancer will be diagnosed in 2006 in the United States alone, and 90% of patients with advanced cancer will experience significant, life-altering cancer-induced pain. Bone cancer pain is the most common pain in patients with advanced cancer as most common tumors including breast, prostate, and lung have a remarkable affinity to metastasize to bone. Once tumors metastasize to bone they are a major cause of morbidity and mortality as the tumor induces significant skeletal remodeling, pain and anemia, which reduce the survival and quality of life of the patient. Currently, the factors that drive cancer pain are poorly understood; however, several recently introduced models of cancer pain are not only providing insight into the mechanisms that drive bone cancer pain but are guiding the development of novel mechanism-based therapies to treat the pain and skeletal remodeling that accompanies metatstatic bone cancer. As analgesics can also influence disease progression, findings from these studies may lead to therapies that have the potential to improve the quality of life and survival of patients with skeletal malignancies.

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Section: Tumor-derived Products In Generation Of Bone Cancer Painmentioning

confidence: 84%

Section: Tumor-derived Products In Generation Of Bone Cancer Painmentioning

confidence: 84%

Similarities and Differences in Tumor Growth, Skeletal Remodeling and Pain in an Osteolytic and Osteoblastic Model of Bone Cancer

Halvorson

Sevcik

Ghilardi³

et al. 2006

The Clinical Journal of Pain

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“…The nocifensive behavior and edema induced by scorpion venom injection into rat hindpaw was reduced by either B 2 or B 1 receptor antagonist given 30 min prior to toxin into the paw (572). In a murine model of bone cancer pain, selective antagonism of the B 1 receptor resulted in a diminishment of nociceptive behavior (651). Spontaneous licking observed from day 18 after inoculation of melanoma cells into hindpaws of mice was reduced by local injection of either a B 2 or B 1 receptor antagonist (216).…”

Section: A) Role Of Bradykinin Receptors In Nocifensive Behavior In-mentioning

confidence: 98%

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pethő

Reeh

2012

Physiological Reviews

234

200

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Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation or excitation by these substances of nociceptive nerve endings or fibers implicates generation of action potentials which then travel to the central nervous system and may induce pain sensation. Sensitization of nociceptors refers to their increased responsiveness to either thermal, mechanical, or chemical stimuli that may be translated to corresponding hyperalgesias. This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons. Manifestations, receptor molecules, and intracellular signaling mechanisms of the effects of these mediators are discussed in detail. With regard to signaling, most data reported have been obtained from transfected nonneuronal cells and somata of cultured sensory neurons as these structures are more accessible to direct study of sensory and signal transduction. The peripheral processes of sensory neurons, where painful stimuli actually affect the nociceptors in vivo, show marked differences with respect to biophysics, ultrastructure, and equipment with receptors and ion channels compared with cellular models. Therefore, an effort was made to highlight signaling mechanisms for which supporting data from molecular, cellular, and behavioral models are consistent with findings that reflect properties of peripheral nociceptive nerve endings. Identified molecular elements of these signaling pathways may serve as validated targets for development of novel types of analgesic drugs.

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“…Moreover, pharmacologic blockade of the B 1 R is effective in reducing pain-related behaviors at both early and advanced stages of bone cancer [12]. Studies performed by our group [13] and by Esseghir et al [14] have described the expression of the B 1 R in human breast tumors.…”

Section: Introductionmentioning

confidence: 98%

Stimulation of the bradykinin B1 receptor induces the proliferation of estrogen-sensitive breast cancer cells and activates the ERK1/2 signaling pathway

Molina

Matus

Astroza

et al. 2009

Breast Cancer Res Treat

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Kinin peptides exert multiple biological effects by binding to two types of G protein-coupled receptors known as B 1 (B 1 R) and B 2 receptors. Expression of the B 1 R in human breast cancer was recently reported, but up to now the consequences of its stimulation are unknown. Our aims were (1) to investigate the capacity of B 1 R to trigger cell proliferation in breast cancer cells, (2) to explore some of the downstream events occurring after B 1 R stimulation that may be linked to cell proliferation, and (3) to determine whether human breast tumors express potentially active B 1 R assessed by the binding of a radiolabeled agonist. Breast cancer cells expressed both the mRNA and the immunoreactive protein of B 1 R that once stimulated triggered cell proliferation at nanomolar concentrations of the ligand. Inhibitor studies suggested that the proliferative effects depend on the activity of epidermal growth factor receptor and subsequent ERK1/2 mitogenactivated protein kinases phosphorylation. B 1 R binding sites, were detected in 3/4 fibroadenomas, in 4/4 ductal carcinomas in situ and in 11/13 invasive ductal carcinomas. The B 1 R-epidermal growth factor receptor crosstalk may be a key interaction that maintains tumor growth, and antagonism of B 1 R may be a valuable alternative for the treatment of breast cancer.

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Analgesic Efficacy of Bradykinin B1 Antagonists in a Murine Bone Cancer Pain Model

Cited by 46 publications

References 16 publications

Similarities and Differences in Tumor Growth, Skeletal Remodeling and Pain in an Osteolytic and Osteoblastic Model of Bone Cancer

Similarities and Differences in Tumor Growth, Skeletal Remodeling and Pain in an Osteolytic and Osteoblastic Model of Bone Cancer

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Stimulation of the bradykinin B1 receptor induces the proliferation of estrogen-sensitive breast cancer cells and activates the ERK1/2 signaling pathway

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