Prevention of granulocyte-colony stimulating factor (G-CSF) induced bone pain using double histamine blockade

Gavioli, Elizabeth Marie; Abrams, Misty

doi:10.1007/s00520-016-3465-y

Cited by 32 publications

(30 citation statements)

References 8 publications

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“…sensory neurons that detect noxious stimuli in bone). Agents that have been reported to sensitize bone nociceptors include bradykinin, endothelins, epidermal growth factor, glial cell line‐derived neurotrophic factor, histamine, nerve growth factor (NGF), prostaglandins, tumour necrosis factor and vascular endothelial growth factor . Probably the best studied factor that has been examined in bone pain in both preclinical and human clinical studies is NGF.…”

Section: Sensitization Of Nociceptors Innervating Bonementioning

confidence: 99%

Mechanisms that drive bone pain across the lifespan

Mantyh

2018

Brit J Clinical Pharma

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Disorders of the skeleton are frequently accompanied by bone pain and a decline in the functional status of the patient. Bone pain occurs following a variety of injuries and diseases including bone fracture, osteoarthritis, low back pain, orthopedic surgery, fibrous dysplasia, rare bone diseases, sickle cell disease and bone cancer. In the past 2 decades, significant progress has been made in understanding the unique population of sensory and sympathetic nerves that innervate bone and the mechanisms that drive bone pain. Following physical injury of bone, mechanotranducers expressed by sensory nerve fibres that innervate bone are activated and sensitized so that even normally non-noxious loading or movement of bone is now being perceived as noxious. Injury of the bone also causes release of factors that; directly excite and sensitize sensory nerve fibres, upregulate proalgesic neurotransmitters, receptors and ion channels expressed by sensory neurons, induce ectopic sprouting of sensory and sympathetic nerve fibres resulting in a hyper-innervation of bone, and central sensitization in the brain that amplifies pain. Many of these mechanisms appear to be involved in driving both nonmalignant and malignant bone pain. Results from human clinical trials suggest that mechanism-based therapies that attenuate one type of bone pain are often effective in attenuating pain in other seemingly unrelated bone diseases. Understanding the specific mechanisms that drive bone pain in different diseases and developing mechanism-based therapies to control this pain has the potential to fundamentally change the quality of life and functional status of patients suffering from bone pain.

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Section: Sensitization Of Nociceptors Innervating Bonementioning

confidence: 99%

Mechanisms that drive bone pain across the lifespan

Mantyh

2018

Brit J Clinical Pharma

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“…HF51116 interrupts the SDF-1α/CXCR4 axis to mobilize more HSCs than is achieved using G-CSF alone. G-CSF shows inter-individual variability and causes bone pain due to its toxic side effects on the BM microenvironment (38,39), and it also require a 4-day standard treatment, which might be too long a treatment duration. The stronger HSC-mobilization activity of HF51116 provides the possibility of reducing the combinatory dose of G-CSF.…”

Section: Discussionmentioning

confidence: 99%

A Novel Small Molecule CXCR4 Antagonist Potently Mobilizes Hematopoietic Stem Cells in Mice and Monkeys

Fang

Mao

et al. 2020

Preprint

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Background Hematopoietic stem cell (HSC) transplantation is an effective treatment strategy for many types of diseases. Peripheral blood (PB) is the most commonly used source of bone marrow (BM)-derived stem cells for current HSC transplantation. However, PB usually contains very few HSCs under normal conditions, as these cells are normally retained within the BM. This retention depends on the interaction between the CXC chemokine receptor 4 (CXCR4) expressed on the HSCs and its natural chemokine ligand, stromal cell-derived factor (SDF)-1α (also named CXCL12) present in the BM stromal microenvironment. In clinical practice, blocking this interaction with a CXCR4 antagonist can induce the rapid mobilization of HSCs from the BM into the PB.Methods C3H/HEJ, DBA/2, CD45.1+, CD45.2+ mice and monkeys were employed in colony-forming unit (CFU) assays, flow cytometry assays, and competitive/non-competitive transplantation assays, to assess the short-term mobilization efficacy of HF51116 and the long-term repopulating (LTR) ability of HSCs. Kinetics of different blood cells and the concentration of HF51116 in PB were also explored by blood routine examinations and pharmacokinetic assays. Results In this paper, we report that a novel small molecule CXCR4 antagonist, HF51116, which was designed and synthesized by our laboratory, can rapidly and potently mobilize HSCs from BM to PB in mice and monkeys. HF51116 not only mobilized HSCs when used alone but also synergized with the mobilizing effects of granulocyte-colony stimulating factor (G-CSF) after co-administration. Following mobilization by HF51116 and G-CSF, the long-term repopulating (LTR) and self-renewing HSCs were sufficiently engrafted in primary and secondary lethally irradiated mice and were able to rescue and support long-term mouse survival. In monkeys, HF51116 exhibited strong HSC mobilization activity and quickly reached the highest in vivo blood drug concentration. Conclusions These results demonstrate that HF51116 is a new promising stem cell mobilizer which specifically targets CXCR4 and merits further preclinical and clinical studies.

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“…The mechanisms of bone pain secondary to G-CSF are not fully known but recent studies have been reported to range from 19 % to 59 %. Bone pain develops in patients treated with pegfi lgrastim and fi lgrastim (2,7,8,11,20,21). On account of bone pain is a well-known complication of G-CSF, pain is treated with drugs (8,9,11,20,21,22).…”

Section: Discussionmentioning

confidence: 99%

“…The most commonly used G-CSF preparations in Turkey and worldwide are fi lgrastim and lenograstim (6). Patients may experience adverse effects including headache, bone pain, myalgia and arthralgia related to G-CSF which are usually managed using pharmacological agents (3,(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%