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Neuroscientist. 2014 Oct;20(5):546-62. doi: 10.1177/1073858414525828. Epub 2014 Mar 24.

The neurobiology of cancer pain.

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Department of Oral Maxillofacial Surgery, New York University College of Dentistry, New York, NY, USA Department of Neuroscience & Physiology, New York University School of Medicine, New York, NY, USA Bluestone Center for Clinical Research, New York University, NY, USA


The global burden of cancer pain is enormous and opioids, despite their side effects, remain the primary therapeutic approach. The cause of cancer pain is unknown. Mechanisms driving cancer pain differ from those mechanisms responsible for inflammatory and neuropathic pain. The prevailing hypothesis put forward to explain cancer pain posits that cancers generate and secrete mediators which sensitize and activate primary afferent nociceptors in the cancer microenvironment. Moreover, cancers induce neurochemical reorganization of the spinal cord, which contributes to spontaneous activity and enhanced responsiveness. The purpose of this review, which covers clinical and preclinical studies, is to highlight those peripheral and central mechanisms responsible for cancer pain. The challenges facing neuroscientists and clinicians studying and ultimately treating cancer pain are discussed.


cancer; cancer pain; pain; sensory system; tumor

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