BDNF parabrachio-amygdaloid pathway in morphine-induced analgesia

Maysa Sarhan, Sophie Anne Pawlowski, Florent Barthas, Ipek Yalcin, Jennifer Kaufling, Hugues Dardente, Venetia Zachariou, Ralph Joseph Dileone, Michel Barrot, Pierre Veinante

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

In addition to its neurotrophic role, brain-derived neurotrophic factor (BDNF) is involved in a wide array of functions, including anxiety and pain. The central amygdaloid nucleus (CeA) contains a high concentration of BDNF in terminals, originating from the pontine parabrachial nucleus. Since the spino-parabrachio-amygdaloid neural pathway is known to convey nociceptive information, we hypothesized a possible involvement of BDNF in supraspinal pain-related processes. To test this hypothesis, we generated localized deletion of BDNF in the parabrachial nucleus using local bilateral injections of adeno-associated viruses in adult floxed-BDNF mice. Basal thresholds of thermal and mechanical nociceptive responses were not altered by BDNF loss and no behavioural deficit was noticed in anxiety and motor tests. However, BDNF-deleted animals displayed a major decrease in the analgesic effect of morphine. In addition, intra-CeA injections of the BDNF scavenger TrkB-Fc in control mice also decreased morphine-induced analgesia. Finally, the number of c-Fos immunoreactive nuclei after acute morphine injection was decreased by 45% in the extended amygdala of BDNF-deleted animals. The absence of BDNF in the parabrachial nucleus thus altered the parabrachio-amygdaloid pathway. Overall, our study provides evidence that BDNF produced in the parabrachial nucleus modulates the functions of the parabrachio-amygdaloid pathway in opiate analgesia.

Original languageEnglish
Pages (from-to)1649-1660
Number of pages12
JournalInternational Journal of Neuropsychopharmacology
Volume16
Issue number7
DOIs
StatePublished - Aug 2013

Keywords

  • Brain-derived neurotrophic factor
  • extended amygdala
  • morphine
  • pain
  • parabrachio-amygdaloid pathway

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