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

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.

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S186 INVOLVEMENT OF KAPPA AND DELTA OPIOID RECEPTORS IN THE ANTINOCICEPTIVE EFFECT OF CROTALPHINE IN A BONE CANCER PAIN MODEL

European Journal of Pain Supplements ◽

10.1016/s1754-3207(11)70761-1 ◽

2011 ◽

Vol 5 (1) ◽

pp. 221

Author(s):

V.P. Gutierrez ◽

P. Brigatte ◽

V.O. Zambelli ◽

G. Picolo ◽

J.S.D. Carvalho ◽

...

Keyword(s):

Cancer Pain ◽

Opioid Receptors ◽

Antinociceptive Effect ◽

Bone Cancer ◽

Bone Cancer Pain ◽

Pain Model ◽

Delta Opioid Receptors

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Intrathecal Substance P-Saporin in the Dog

Anesthesiology ◽

10.1097/aln.0b013e3182a95188 ◽

2013 ◽

Vol 119 (5) ◽

pp. 1178-1185 ◽

Cited By ~ 33

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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The antinociceptive effect of systemic administration of a combination of low-dose tramadol and dexmedetomidine in a rat model of bone cancer pain

European Journal of Anaesthesiology ◽

10.1097/eja.0b013e3283624a0f ◽

2014 ◽

Vol 31 (1) ◽

pp. 30-34 ◽

Cited By ~ 4

Author(s):

Xiaomin Yuan ◽

Jingxiang Wu ◽

Qiong Wang ◽

Meiying Xu

Keyword(s):

Cancer Pain ◽

Rat Model ◽

Low Dose ◽

Antinociceptive Effect ◽

Bone Cancer ◽

Systemic Administration ◽

Bone Cancer Pain

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

Frontiers in Neuroscience ◽

10.3389/fnins.2021.696861 ◽

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.

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