<p>Effect of glutaminase inhibition on cancer-induced bone pain</p>

Cancer-induced bone pain is a severe and complex pain caused by metastases to bone in cancer patients. The aim of this study was to investigate the analgesic effect of scutellarin on cancer-induced bone pain in rat models by intrathecal injection of Walker 256 carcinoma cells. Mechanical allodynia was determined by paw withdrawal threshold in response to mechanical stimulus, and thermal hyperalgesia was indicated by paw withdrawal latency in response to noxious thermal stimulus. The paw withdrawal threshold and paw withdrawal latencies were significantly decreased after inoculation of tumor cells, whereas administration of scutellarin significantly attenuated tumor cell inoculation-induced mechanical and heat hyperalgesia. Tumor cell inoculation-induced tumor growth was also significantly abrogated by scutellarin. Ca2+/calmodulin-dependent protein kinase II is a multifunctional kinase with up-regulated activity in bone pain models. The activation of Ca2+/calmodulin-dependent protein kinase II triggers phosphorylation of cAMP-response element binding protein. Scutellarin significantly reduced the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein in cancer-induced bone pain rats. Collectively, our study demonstrated that scutellarin attenuated tumor cell inoculation-induced bone pain by down-regulating the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein. The suppressive effect of scutellarin on phosphorylated-Ca2+/calmodulin-dependent protein kinase II/phosphorylated-cAMP-response element binding protein activation may serve as a novel therapeutic strategy for CIBP management.

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Targeting G-Protein Signaling for the Therapeutics of Prostate Tumor Bone Metastases and the Associated Chronic Bone Pain

10.21236/ada609444 ◽

2014 ◽

Author(s):

Songhai Chen ◽

Yuanchao Ye

Keyword(s):

Bone Metastases ◽

G Protein ◽

Bone Pain ◽

Prostate Tumor ◽

G Protein Signaling ◽

Protein Signaling

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[177Lu]Lu-DOTA-ZOL bone pain palliation in patients with skeletal metastases from various cancers: efficacy and safety results

EJNMMI Research ◽

10.1186/s13550-020-00709-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Madhav Prasad Yadav ◽

Sanjana Ballal ◽

Marian Meckel ◽

Frank Roesch ◽

Chandrasekhar Bal

Keyword(s):

Overall Survival ◽

Pain Assessment ◽

Bone Pain ◽

Performance Status ◽

Response Assessment ◽

Assessment Criteria ◽

Skeletal Metastases ◽

Efficacy And Safety ◽

Pain Palliation ◽

Global Pain

Abstract Background [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy are limited. The objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers. Methods In total, 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3–2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR 8–14 months). The primary outcome endpoint was response assessment according to the visual analogue score (VAS). Secondary endpoints included analgesic score (AS), global pain assessment score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky performance status, overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0. Results In total, 40 patients (15 males and 25 females) with a mean age of 46.6 ± 15.08 years (range 24–78 years) were treated with either 1 (N = 15) or 2 (N = 25) cycles of [177Lu]Lu-DOTA-ZOL. According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal, and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty-eight patients died and the estimated median overall survival was 13 months (95% CI 10–14 months). A significant improvement was observed in the VAS, AS, and ECOG status when compared to baseline. None of the patients experienced grade III/IV haematological, kidney, or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy. Conclusion [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.

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Bone Pain in Multiple Myeloma (BPMM)—A Protocol for a Prospective, Longitudinal, Observational Study

Cancers ◽

10.3390/cancers13071596 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1596

Author(s):

Marta Diaz-delCastillo ◽

Rebecca E. Andrews ◽

Aritri Mandal ◽

Thomas L. Andersen ◽

Andrew D. Chantry ◽

...

Keyword(s):

Quality Of Life ◽

Multiple Myeloma ◽

Observational Study ◽

Bone Turnover ◽

Bone Pain ◽

Subjective Experience ◽

Prospective Longitudinal ◽

Bone Turnover Biomarkers

Multiple myeloma (MM) is a bone marrow neoplasia that causes bone pain in 70% patients. While preclinical models of MM have suggested that both nerve sprouting and nerve injury may be causative for the pain, there is a lack of clinical data. Thus, the primary aims of this clinical study are: (1) to provide a deep characterization of the subjective experience of pain and quality of life in MM patients; (2) to investigate disturbances in the bone innervation of MM patients. Secondary aims include exploring correlations between pain and serum inflammatory and bone turnover biomarkers. In a prospective, observational study (clinicaltrials.gov: NCT04273425), patients with suspected MM requiring a diagnostic iliac crest biopsy at Sheffield Teaching Hospital (UK) are invited to participate. Consenting patients answer seven standardized questionnaires assessing pain, quality of life and catastrophizing. Bone turnover biomarkers and inflammatory cytokines are measured in fasting serum samples, and bone innervation is evaluated in diagnostic biopsies. MM patients are invited to a follow-up upon completion of first line treatment. This will be the first deep characterization of pain in MM patients and its correlation with disturbances in bone innervation. Understanding how bone turnover and inflammation correlate to pain in MM is crucial to identify novel analgesic targets for this condition.

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Effective control of bone pain by octreotide in a patient with metastatic gastrinoma

The Medical Journal of Australia ◽

10.5694/j.1326-5377.1996.tb122271.x ◽

1996 ◽

Vol 164 (12) ◽

pp. 725-727 ◽

Cited By ~ 9

Author(s):

John R Burgess ◽

Venkateswaran Parameswaran ◽

Timothy M Greenaway ◽

Joseph J Shepherd ◽

Fiona J Murton

Keyword(s):

Bone Pain ◽

Effective Control

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Pegfilgrastim-Induced Bone Pain: A Review on Incidence, Risk Factors, and Evidence-Based Management

Annals of Pharmacotherapy ◽

10.1177/1060028017706373 ◽

2017 ◽

Vol 51 (9) ◽

pp. 797-803 ◽

Cited By ~ 7

Author(s):

Donald C. Moore ◽

Annie E. Pellegrino

Keyword(s):

Risk Factors ◽

Bone Pain ◽

English Language ◽

Data Extraction ◽

Treatment Modalities ◽

Management Options ◽

Data Synthesis ◽

Pharmacological Management ◽

Study Selection ◽

Incidence Risk

Objective: To review the incidence, risk factors, and management of pegfilgrastim-induced bone pain (PIBP). Data Sources: PubMed was searched from 1980 to March 31, 2017, using the terms pegfilgrastim and bone pain. Study Selection and Data Extraction: English-language, human studies and reviews assessing the incidence, risk factors, and management of PIBP were incorporated. Data Synthesis: A total of 3 randomized, prospective studies and 2 retrospective studies evaluated pharmacological management of PIBP. Naproxen compared with placebo demonstrated a reduction in the degree, incidence, and duration of bone pain secondary to pegfilgrastim. Loratadine was not effective in reducing the incidence of bone pain prophylactically, but a retrospective study evaluating dual antihistamine blockade with loratadine and famotidine demonstrated a decreased incidence in bone pain when administered before pegfilgrastim. Conclusion: Naproxen is effective at managing PIBP. Although commonly used, antihistamines have a paucity of data supporting their use. Dose reductions of pegfilgrastim and opioids may also be potential management options; however, data supporting these treatment modalities are scarce.

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