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

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

Research output: Contribution to journalArticle

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

Fingerprint

Analgesia
Hypersensitivity
Neurons
Mouth Neoplasms
Opioid Receptors
Neoplasms
Hot Temperature
Hyperalgesia
Opioid Analgesics
Pain
Nociceptors
Pharmacology
Cancer Pain

Keywords

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

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology

Cite this

Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity. / Ye, Yi; Dang, Dongmin; Viet, Chi T.; Dolan, John C.; Schmidt, Brian.

In: Journal of Pain, Vol. 13, No. 6, 06.2012, p. 524-531.

Research output: Contribution to journalArticle

Ye, Yi ; Dang, Dongmin ; Viet, Chi T. ; Dolan, John C. ; Schmidt, Brian. / Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity. In: Journal of Pain. 2012 ; Vol. 13, No. 6. pp. 524-531.
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