scholarly journals Curcumin Exerts Antinociceptive Effects in Cancer-Induced Bone Pain via an Endogenous Opioid Mechanism

2021 ◽  
Vol 15 ◽  
Author(s):  
Guanghai Zhao ◽  
Yongqiang Shi ◽  
Chaoyang Gong ◽  
Taicong Liu ◽  
Wei Nan ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Bone Pain ◽  
Antinociceptive Effect ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Drg Neurons ◽  
Advanced Cancer Patients ◽  
Endogenous Opioid ◽  
Analgesic Effects ◽  
Antinociceptive Effects

Cancer pain is one of the main complications in advanced cancer patients, and its management is still challenging. Therefore, there is an urgent need to develop novel pharmacotherapy for cancer pain. Several natural products have attracted the interest of researchers. In previous studies, curcumin has proved to exhibit antitumor, antiviral, antioxidant, anti-inflammatory, and analgesic effects. However, the analgesic mechanism of curcumin has not been elucidated. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of curcumin in cancer-induced bone pain. Our results showed that consecutive curcumin treatment (30, 60, 120 mg/kg, i.p., twice daily for 11 days) produced significant analgesic activity, but had no effect on the progress of the bone cancer pain. Notably, pretreatment with naloxone, a non-selective opioid receptor antagonist, markedly reversed the antinociceptive effect induced by curcumin. Moreover, in primary cultured rat dorsal root ganglion (DRG) neurons, curcumin significantly up-regulated the expression of proopiomelanocortin (Pomc) and promoted the release of β-endorphin and enkephalin. Furthermore, pretreatment with the antiserum of β-endorphin or enkephalin markedly attenuated curcumin-induced analgesia in cancer-induced bone pain. Our present study, for the first time, showed that curcumin attenuates cancer-induced bone pain. The results also suggested that stimulation of expression of DRG neurons β-endorphin and enkephalin mediates the antinociceptive effect of curcumin in pain hypersensitivity conditions.

scholarly journals The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat

2018 ◽  
Vol 71 (5) ◽  
pp. 816-825 ◽  
Author(s):  
Sebastian Lux ◽  
Nicolas Lobos ◽  
Carolyne Lespay‐Rebolledo ◽  
Edison Salas‐Huenuleo ◽  
Marcelo J. Kogan ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Antinociceptive Effect ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Silent Information Regulator 1

scholarly journals Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Mao-yin Zhang ◽  
Yue-peng Liu ◽  
Lian-yi Zhang ◽  
Dong-mei Yue ◽  
Dun-yi Qi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cancer Pain ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Bone Cancer ◽  
Microglial Cells ◽  
Bone Cancer Pain ◽  
Enzyme Linked Immunosorbent Assay ◽  
Analgesic Effects ◽  
Before And After

Objective. The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI).Methods. Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg) were administrated intragastrically at early phase of postoperation (before pain appearance) and later phase of postoperation (after pain appearance), respectively. The concentrations of TNF-α, IL-1β, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment.Results. TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-αand IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1βincrease.Conclusion. This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase.

Analgesic effects of neurotensin agonists in a rat bone cancer pain model

2016 ◽  
Author(s):  
Louis Dore-Savard ◽  
Pascal Tetreault ◽  
Melisange Roux ◽  
Marylie Martel ◽  
Myriam Lemire ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Weight Bearing ◽  
Bone Cancer ◽  
Opioid Analgesics ◽  
Bone Cancer Pain ◽  
Intractable Pain ◽  
Analgesic Effects ◽  
Selective Agonist ◽  
Neurotensin Receptors ◽  
Pain Models

Bone metastases are a source of intractable pain, resistant to conventional opioid and non-opioid analgesics. The neurotensin system represents a potential pathway toward bone cancer pain (BCP) relieve via the inhibition of its receptors NTS1 and NTS2. Capitalizing on our recent results using neurotensin analogs in inflammatory and neuropathic pain models, we here show, for the first time, a potential role for neurotensin receptors agonists in the treatment of BCP. The novel non-selective agonist JMV-2009 (300 μg/kg) reversed mechanical allodynia in our rodent BCP model at both early and late stages of the disease. The NTS2-selective agonist JMV-431 (90 μg/kg), in addition to anti-allodynia, also had an effect on weight bearing deficits. In parallel, we tested proven analgesics from several classes to put the effect of neurotensin analogs in perspective and found that morphine (3 mg/kg), tramadol (15 mg/kg) and amitriptyline (10 mg/kg) had mild effects on BCP while the cannabinoid nabilone (1 mg/kg) significantly reversed both allodynia and weight bearing deficits. Taken together, our results affirm the potential of the modulation of the neurotensin system for the development of new analgesics for the treatment of bone cancer pain.

scholarly journals Preconditioning with hydrogen sulfide prevents bone cancer pain in rats through a proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway

2017 ◽  
Vol 243 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Li Zhuang ◽  
Ke Li ◽  
Gaowei Wang ◽  
Tao Shou ◽  
Chunlin Gao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cancer Pain ◽  
Rat Model ◽  
Mechanical Allodynia ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Kinase Pathway

Bone cancer pain (BCP) is a severe type of hyperpathic pain occurring with primary bone tumors or advanced cancers which metastasize to bones. BCP can detrimentally reduce quality of life and presents a challenge to modern medicine. Studies have shown that exogenous H2S may act as a neuroprotectant to protect against some diseases in central nervous system. The preset study aimed to investigate the antinociceptive effect of H2S in BCP. We first measured the changes of serum H2S in patients with BCP and analyzed the relationship between them, then investigated the effect of H2S preconditioning on BCP, and explored the mechanism in rat model. Our results revealed that serum H2S level was negatively correlated with pain scores. In the rat model of BCP, preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. The mechanism of H2S preconditioning may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. Impact statement Bone cancer pain (BCP) significantly decreases the life quality of patients or their life expectancy and causes a severe health burden to the society. However, as the exact mechanism of BCP is still poorly understood, no effective treatment has been developed yet. There are some pain medicines now, but they have some inevitable side effects. Additional therapeutic strategies are urgently needed. First, we revealed that preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. Second, the mechanism of H2S preconditioning was elucidated. It may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. This novel finding may significantly help us to understand the difference between the roles of endogenous H2S and exogenous H2S in the development of BCP and present us a new strategy of pain management.

Analgesic effects of microRNA‐129‐5p against bone cancer pain through the EphB1/EphrinB2 signaling pathway in mice

2018 ◽  
Vol 120 (3) ◽  
pp. 2876-2885 ◽  
Author(s):  
Shao‐Nan Yu ◽  
Gui‐Feng Liu ◽  
Long‐Yun Li ◽  
Guo‐Qing Zhao ◽  
Lin Liu ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Signaling Pathway ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Analgesic Effects

Analgesic effects of a soy-containing diet in three murine bone cancer pain models

2004 ◽  
Vol 5 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Chengshui Zhao ◽  
Paul W Wacnik ◽  
Jill M Tall ◽  
David C Johns ◽  
George L Wilcox ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Analgesic Effects ◽  
Pain Models

scholarly journals Analgesic effects of adenylyl cyclase inhibitor NB001 on bone cancer pain in a mouse model

2016 ◽  
Vol 12 ◽  
pp. 174480691665240 ◽  
Author(s):  
Wen-bo Kang ◽  
Qi Yang ◽  
Yan-yan Guo ◽  
Lu Wang ◽  
Dong-sheng Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cancer Pain ◽  
Adenylyl Cyclase ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Analgesic Effects ◽  
Adenylyl Cyclase Inhibitor

scholarly journals Intrathecal Substance P-Saporin in the Dog

2013 ◽  
Vol 119 (5) ◽  
pp. 1178-1185 ◽  
Author(s):  
Dorothy Cimino Brown ◽  
Kimberly Agnello
Keyword(s):  
Substance P ◽  
Cancer Pain ◽  
Antinociceptive Effect ◽  
Intrathecal Injection ◽  
Bone Cancer ◽  
Standard Of Care ◽  
Bone Cancer Pain ◽  
Controlled Study ◽  
Control Group ◽  
Analgesic Therapy

Abstract Background: Substance P-saporin (SP-SAP), a chemical conjugate of substance P and a recombinant version of the ribosome-inactivating protein, saporin, when administered intrathecally, acts as a targeted neurotoxin producing selective destruction of superficial neurokinin-1 receptor–bearing cells in the spinal dorsal horn. The goal of this study was to provide proof-of-concept data that a single intrathecal injection of SP-SAP could safely provide effective pain relief in spontaneous bone cancer pain in companion (pet) dogs. Methods: In a single-blind, controlled study, 70 companion dogs with bone cancer pain were randomized to standard-of-care analgesic therapy alone (control, n = 35) or intrathecal SP-SAP (20–60 µg) in addition to standard-of-care analgesic therapy (n = 35). Activity, pain scores, and videography data were collected at baseline, 2 weeks postrandomization, and then monthly until death. Results: Although the efficacy results at the 2-week postrandomization point were equivocal, the outcomes evaluated beyond 2 weeks revealed a positive effect of SP-SAP on chronic pain management. Significantly, more dogs in the control group (74%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization than dogs that were treated with SP-SAP (24%; P < 0.001); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with SP-SAP (P < 0.01). Conclusion: Intrathecal administration of SP-SAP in dogs with bone cancer produces a time-dependent antinociceptive effect with no evidence of development of deafferentation pain syndrome which can be seen with neurolytic therapies.

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