What pain tells us about cancer

Schmidt, Brian L.

doi:10.1097/j.pain.0000000000000099

Cited by 27 publications

(22 citation statements)

References 29 publications

(33 reference statements)

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“…Sensory innervation is reported to be favored over sympathetic innervation in HNSCC 41 , pancreatic cancer 48 and painful non-malignant conditions 49 . Increased density of innervation is associated with pain, lymph node metastasis and poor prognosis in a number of cancer types 6,8 . Nine pain and metastasis genes have roles in axonogenesis and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Oncogenes overexpressed in metastatic oral cancers from patients with pain: potential pain mediators released in exosomes

Bhattacharya

Veeramachaneni

Dolgalev

et al. 2020

Sci Rep

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Oral cancer patients experience pain at the site of the primary cancer. Patients with metastatic oral cancers report greater pain. Lack of pain identifies patients at low risk of metastasis with sensitivity = 0.94 and negative predictive value = 0.89. In the same cohort, sensitivity and negative predictive value of depth of invasion, currently the best predictor, were 0.95 and 0.92, respectively. Cancer pain is attributed to cancer-derived mediators that sensitize neurons and is associated with increased neuronal density. We hypothesized that pain mediators would be overexpressed in metastatic cancers from patients reporting high pain. We identified 40 genes overexpressed in metastatic cancers from patients reporting high pain (n = 5) compared to N0 cancers (n = 10) and normal tissue (n = 5). The genes are enriched for functions in extracellular matrix organization and angiogenesis. They have oncogenic and neuronal functions and are reported in exosomes. Hierarchical clustering according to expression of neurotrophic and axon guidance genes also separated cancers according to pain and nodal status. Depletion of exosomes from cancer cell line supernatant reduced nociceptive behavior in a paw withdrawal assay, supporting a role for exosomes in cancer pain. The identified genes and exosomes are potential therapeutic targets for stopping cancer and attenuating pain.

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Section: Discussionmentioning

confidence: 99%

“…Oral cancer pain is attributed to sensitization or activation of primary afferent neurons by mediators released from the cancer and microenvironment. Cancers also induce sprouting of sensory and sympathetic nerves into the microenvironment 6,8 . We reported previously that patients with metastatic (N+) cancers experienced greater pain 9 .…”

mentioning

confidence: 99%

Oncogenes overexpressed in metastatic oral cancers from patients with pain: potential pain mediators released in exosomes

Bhattacharya

Veeramachaneni

Dolgalev

et al. 2020

Sci Rep

Self Cite

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“…The brain is not only the central hub for neural communications in the body, but it also integrates signals from the outside world. On the one hand, cancer-associated pain is the illustration that neuronal information from tumors can travel to the brain (56). On the other hand, external stimuli and psychosocial interactions are functionally integrated at the cortical level and result in both rapid and chronic adaptive changes in the functioning of the autonomic, sensory, and motor nervous systems.…”

Section: A Higher Regulation Level Of Cancer Developmentmentioning

confidence: 99%

Tumor Neurobiology and the War of Nerves in Cancer

et al. 2019

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Nerves are emerging regulators of cancer progression. Cancer cells induce the outgrowth of nerves in the tumor microenvironment through the release of neurotrophic factors, and in return nerves liberate neurotransmitters that activate cancer growth and dissemination. Although sympathetic nerves drive tumor angiogenesis via the liberation of noradrenaline, sensory and parasympathetic nerves stimulate cancer stem cells. Interestingly, recent evidence indicates that parasympathetic nerves can eventually inhibit tumor progression, suggesting a yin-yang type of regulation of cancer by nerves. From a broader perspective, the question of a higher level of control of cancer development by the central nervous system should be raised. Signifi cance:Nerves are emerging regulators of cancer initiation, progression, and metastasis. Here, we review the evidence to date and explore the basic and clinical ramifi cations of these fi ndings.

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“…As a result, CP is increasingly seen as a unique entity different from other pain states 14 . Focusing on the treatment of CP and its underlying pathophysiology, argues Schmidt, may lead to a new breakthrough in not only the treatment of pain but also novel approaches to the treatment of cancer itself.…”

Section: New Insights Into the Neurobiology Of Cancer Pain: Cancer Pamentioning

confidence: 99%

Recent advances in understanding and managing cancer pain

Chwistek

2017

F1000Res

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Cancer pain remains a significant clinical problem worldwide. Causes of cancer pain are multifactorial and complex and are likely to vary with an array of tumor-related and host-related factors and processes. Pathophysiology is poorly understood; however, new laboratory research points to cross-talk between cancer cells and host’s immune and neural systems as an important potential mechanism that may be broadly relevant to many cancer pain syndromes. Opioids remain the most effective pharmaceuticals used in the treatment of cancer pain. However, their role has been evolving due to emerging awareness of risks of chronic opioid therapy. Despite extensive research efforts, no new class of analgesics has been developed. However, many potential therapeutic targets that may lead to the establishment of new pharmaceuticals have been identified in recent years. It is also expected that the role of non-pharmacological modalities of treatment will grow in prominence. Specifically, neuromodulation, a rapidly expanding field, may play a major role in the treatment of neuropathic cancer pain provided that further technological progress permits the development of non-invasive and inexpensive neuromodulation techniques.

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What pain tells us about cancer

Cited by 27 publications

References 29 publications

Oncogenes overexpressed in metastatic oral cancers from patients with pain: potential pain mediators released in exosomes

Oncogenes overexpressed in metastatic oral cancers from patients with pain: potential pain mediators released in exosomes

Tumor Neurobiology and the War of Nerves in Cancer

Recent advances in understanding and managing cancer pain

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