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Advances in Head and Neck Cancer Pain.

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|April 13, 2022
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Summary

Head and neck cancer (HNC) pain significantly impacts quality of life. Targeting shared mechanisms between HNC progression and pain offers new therapeutic strategies for both cancer and pain management.

Keywords:
carcinomafacial painmouth neoplasmnociceptorsperipheral nervessquamous cell

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Area of Science:

  • Oncology
  • Pain Research
  • Cancer Biology

Background:

  • Head and neck cancer (HNC) affects over 890,000 people globally, with a 50% mortality rate.
  • HNC pain, characterized by allodynia, hyperalgesia, and spontaneous pain, severely diminishes patients' quality of life.
  • Pathological features like perineural invasion and lymph node metastasis correlate with increased pain intensity.

Purpose of the Study:

  • To investigate the pathobiology of HNC pain using advanced animal models.
  • To elucidate the role of the tumor microenvironment, including glial and immune cells, in HNC pain signaling.
  • To identify molecular mediators and signaling pathways involved in the cross-talk between HNC and peripheral nerves.

Main Methods:

  • Utilized syngeneic/immunocompetent animal models and a novel mouse model of perineural invasion.
  • Examined the modulation of the tumor microenvironment by glial cells (Schwann cells) and immune cells (neutrophils).
  • Investigated the role of specific molecular mediators such as Brain-derived neurotrophic factor, tumor necrosis factor α, legumain, cathepsin S, and A disintegrin and metalloprotease 17.

Main Results:

  • Demonstrated a functional cross-activation loop between the tumor microenvironment and peripheral nerves via paracrine and autocrine signaling.
  • Identified pronociceptive and protumorigenic mediators secreted by HNC cells and involved in nerve hypersensitivity.
  • Observed a dampened endogenous antinociception system in HNC, including downregulation of resolvins and µ-opioid receptor expression.

Conclusions:

  • Pain and HNC progression share converging biological mechanisms.
  • Targeting the interplay between the tumor microenvironment and peripheral nerves presents a promising strategy for combined cancer treatment and pain management.
  • Therapeutic interventions like resolvin treatment or µ-opioid receptor gene delivery show potential for pain relief in preclinical HNC models.