Scientists turn off chemo pain in laboratory

[Schallen]

Scientists have successfully turned off the excruciating pain that often accompanies a colorectal cancer drug in an animal model.

Chemotherapy induced neuropathic pain (CINP) is a debilitating side effect that can appear as tingling or numbness in the hands and feet, shooting or burning pain in the limbs, or can feel like hot or cold temperature extremes.

In addition to causing patients suffering, CINP is often a limiting factor when it comes to treatment.
"Thanks to the increased efficacy of cancer treatment, there are nearly 14 million cancer survivors in the US," said Daniela Salvemini, a professor at Saint Louis University in the US.

"Many of these survivors suffer from long-term side effects of CINP, for which there are no proven strategies for prevention or treatment," said Salvemini.

Researchers found that the pain pathway associated with this drug was driven by increased expression of an enzyme, adenosine kinase, in astrocytes (a type of central nervous system cell) and decreased adenosine signalling at a key receptor, A3AR.

Researchers found that the pain pathway associated with this drug was driven by increased expression of an enzyme, adenosine kinase, in astrocytes (a type of central nervous system cell) and decreased adenosine signalling at a key receptor, A3AR.

By supplementing this signalling with A3AR agonists, the researchers were able to block the development of CINP without interfering with the anticancer properties of platinum based drugs.

These findings advance researchers' understanding of pain pathways and provide new information about how drugs may be able to treat chemotherapy pain.
Existing A3AR agonists currently are being studied in advanced clinical trials as novel anticancer agents, researchers said.

The research makes a strong case for evaluating those drugs for use together with oxaliplatin to limit CINP while treating cancer.

By supplementing this signalling with A3AR agonists, the researchers were able to block the development of CINP without interfering with the anticancer properties of platinum based drugs.

These findings advance researchers' understanding of pain pathways and provide new information about how drugs may be able to treat chemotherapy pain.
Existing A3AR agonists currently are being studied in advanced clinical trials as novel anticancer agents, researchers said.

The research makes a strong case for evaluating those drugs for use together with oxaliplatin to limit CINP while treating cancer.

http://www.dnaindia.com/health/report-s ... ry-2598324

[NHMike]

I am not familiar with this source. Do you have the base research papers for the article?

[retiredteacher]

Couple more articles:
https://www.slu.edu/news/2018/march/che ... search.php

https://www.eurekalert.org/pub_releases ... 032618.php

[NHMike]

Couple more articles:
https://www.slu.edu/news/2018/march/che ... search.php

https://www.eurekalert.org/pub_releases ... 032618.php

Thanks for the articles. The research paper is paywalled so I'll ask my son if he can get it for me.

[O Stoma Mia]

. The research paper is paywalled so I'll ask my son if he can get it for me.

Here is the Abstract from the paywalled research article:

ABSTRACT - - Development of chemotherapy-induced neuropathic pain (CINP) compromises the use of chemotherapy and greatly impacts thousands of lives. Unfortunately, there are no Food and Drug Administration–approved drugs to prevent or treat CINP. Neuropathological changes within CNS, including neuroinflammation and increased neuronal excitability, are driven by alterations in neuro-glia communication; but, the molecular signaling pathways remain largely unexplored. Adenosine is a potent neuroprotective purine nucleoside released to counteract the consequences of these neuropathological changes. Adenosine signaling at its adenosine receptors (ARs) is dictated by adenosine kinase (ADK) in astrocytes, which provides a cellular sink for the removal of extracellular adenosine. We now demonstrate that chemotherapy (oxaliplatin) in rodents caused ADK overexpression in reactive astrocytes and reduced adenosine signaling at the A3AR subtype (A3AR) within the spinal cord. Dysregulation of ADK and A3AR signaling was associated with increased proinflammatory and neuroexcitatory interleukin-1β expression and activation of nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome, but not putative oxaliplatin-associated GSK3β transcriptional regulation. Intrathecal administration of the highly selective A3AR agonist MRS5698 attenuated IL-1β production and increased the expression of potent anti-inflammatory and neuroprotective IL-10. The effects of MRS5698 were blocked by attenuating IL-10 signaling in rats with intrathecal neutralizing IL-10 antibody and in IL-10−/− knockout mice. These findings provide new molecular insights implicating astrocyte-based ADK-adenosine axis and nucleotide-binding oligomerization domain-like receptor protein 3 in the development of CINP and IL-10 in the mechanism of action of A3AR agonists. These findings strengthen the pharmacological rationale for clinical evaluation of A3AR agonists already in advanced clinical trials as anticancer agents as an adjunct to chemotherapy.

Reference: Chemotherapy-induced pain is promoted by enhanced spinal adenosine kinase levels through astrocyte-dependent mechanisms.
Wahlman, Carriea; Doyle, Timothy, M., Little, Joshua, W.; Luongo, Livioc; Janes, Kalia; Chen, Zhoumoua; Esposito, Emanuelad; Tosh, Dilip, K.; Cuzzocrea, Salvatored; Jacobson, Kenneth, A.; Salvemini, Danielaa,*, PAIN, February 6, 2018
© 2018 International Association for the Study of Pain