Multiple sclerosis drug may relieve chemo pain

Researchers have discovered a molecular pathway linked to a painful side effect of chemotherapy and found that a multiple sclerosis drug may be able to block it.
The discovery was made by Saint Louis University professor of pharmacological and physiological sciences Daniela Salvemini.
"The chemotherapy drug paclitaxel is widely used to treat many forms of cancer, including breast, ovarian and lung cancers," said Salvemini.
"Though it is highly effective, the medication, like many other chemotherapy drugs, frequently is accompanied by a debilitating side effect called chemotherapy induced peripheral neuropathy, or CIPN," said Salvemini.
CIPN 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.

Symptoms may resolve within weeks or months of stopping the chemotherapy treatment or may last for years.

In addition to causing patients suffering, CIPN is often a limiting factor when it comes to treatment.
Physicians estimate that CIPN can occur in 30 to 90 per cent of patients treated with taxanes (the class of drugs that includes paclitaxel) and combination chemotherapies.
Researchers studied the drug paclitaxel, which is also known as Taxol.
They discovered that the pain pathway (the series of interactions between molecular-level components) is dependent on activation of sphingosine 1-phosphate receptor subtype 1 (S1PR1) in the central nervous system by engaging a series of damaging neuro-inflammatory processes leading to pain.

By inhibiting this molecule, they found that they could block and reverse paclitaxel-induced neuropathic pain without interfering with the drug's anticancer effects.
This finding is particularly encouraging because a drug that modulates S1PR1 is already on the market. A medication called FTY720 (Gilenya) is FDA-approved as a therapy for multiple sclerosis.
When Salvemini tested this drug in her lab, she found that the S1PR1 modulator weakened the neuroinflammatory processes, which in turn blocked and reversed neuropathic pain without altering the anticancer properties of paclitaxel.
Further, the beneficial effects of FTY720 were not restricted to paclitaxel but also extended to another chemotherapeutic agent, the platinum based drug oxaliplatin which is widely used for metastatic colon cancer and other gastrointestinal cancers.

While clinical trials will be necessary to determine the safety and efficacy of the drug in treating CIPN, researchers are hopeful that they may be able not only to relieve cancer patients of debilitating pain, but also save more lives by permitting the administration of larger, potentially more effective doses of chemotherapy drugs.
The study was published in the Journal of Biological Chemistry.