Treatment-induced pain in cancer patients


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Patrick Dougherty1
1The University of Texas MD Anderson Cancer Center, Houston, USA

Abstract

In this symposium recent findings on a key patient risk factor for chemotherapy-induced peripheral neuropathy (CIPN) and new insights to the basic mechanisms garnered from pre-clinical studies will be presented.

Patients with chronic CIPN showdepletion of skin innervation that parallels in magnitude the distribution of CIPN symptoms. Surprisingly, it was also discovered that there is a proximal to distal decrease in baseline innervation density in normal volunteers in a pattern that exactly matches that of symptoms in CIPN patients. These findings strongly suggest that baseline innervation density is a latent factor that can predict those at greatest risk for CIPN, and could be used to guide personalised treatment to avoid this complication. Data will be presented showing that patients with deficits in distal innervation density assessed using non-invasive imaging correlate to pre-treatment sensory deficits. Moreover, patients with pre-treatment sensory deficits go on to develop more spontaneous pain during chemotherapy than those who had normal sensory function.

Previous pre-clinical work has shown the involvement of an inflammatory response in CIPN. New data that will be presented in this symposium indicate that Toll-like receptor 4 (TLR4) is a key in triggering this response that leads to CIPN. TLR4 is shown to be expressed on neurons that innervate the skin and to become activated in animals treated with the chemotherapy drug paclitaxel. In addition, a TLR4 antagonist is shown to both reverse pre-established paclitaxel CIPN, and also to prevent its onset when given along with the chemotherapy drug. Even more exciting is that similar findings have been extended to the chemotherapeutics oxaliplatin and bortezomib. The findings here provide a simple unifying hypothesis for all these clinical conditions that could in turn result in a single shared medication for CIPN that would not interfere with the anti-tumour effects of the chemotherapy drugs.

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