Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity

Yi Ye, Dongmin Dang, Chi T. Viet, John C. Dolan, Brian L. Schmidt

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer patients often suffer from pain and most will be prescribed μ-opioids. μ-opioids are not satisfactory in treating cancer pain and are associated with multiple debilitating side effects. Recent studies show that μ and δ opioid receptors are separately expressed on IB4 (-) and IB4 (+) neurons, which control thermal and mechanical pain, respectively. In this study we investigated IB4 (+) and IB4 (-) neurons in mechanical and thermal hypersensitivity in an orthotopic mouse oral cancer model. We used a δ opioid receptor agonist and a P2X 3 antagonist to target IB4 (+) neurons and to demonstrate that this subset plays a key role in cancer-induced mechanical allodynia, but not in thermal hyperalgesia. Moreover, selective removal of IB4 (+) neurons using IB4-saporin impacts cancer-induced mechanical but not thermal hypersensitivity. Our results demonstrate that peripherally administered pharmacological agents targeting IB4 (+) neurons, such as a selective δ-opioid receptor agonist or P2X 3 antagonist, might be useful in treating oral cancer pain. Perspective: To clarify the mechanisms of oral cancer pain, we examined the differential role of IB4 (+) and IB4 (-) neurons. Characterization of these 2 subsets of putative nociceptors is important for further development of effective clinical cancer pain relief.

Original languageEnglish (US)
Pages (from-to)524-531
Number of pages8
JournalJournal of Pain
Volume13
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • NGF
  • cancer pain
  • isolectin B4
  • δ-opioid receptor (DOR)
  • μ-opioid receptor (MOR)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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