Chronic neuropathic pain-like behavior correlates with IL-1β expression and disrupts cytokine interactions in the hippocampus

Adriana Del Rey*, Hau Jie Yau, Anke Randolf, Maria V. Centeno, Johannes Wildmann, Marco Martina, Hugo O. Besedovsky, A. Vania Apkarian

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


We have proposed that neuropathic pain engages emotional learning, suggesting the involvement of the hippocampus. Because cytokines in the periphery contribute to induction and maintenance of neuropathic pain but might also participate centrally, we used 2 neuropathic pain models, chronic constriction injury (CCI) and spared nerve injury (SNI), to investigate the temporal profile of hippocampal cytokine gene expression in 2 rat strains that show different postinjury behavioral threshold sensitivities. SNI induced long-lasting allodynia in both strains, while CCI induced allodynia with time-dependent recovery in Sprague Dawley (SD) and no allodynia in Wistar Kyoto (WK) rats. In WK rats, only SNI induced sustained upregulation of hippocampal interleukin (IL)-1β, while IL-6 expression was transiently increased and no significant changes in IL-1ra expression were detected. Conversely, in SD rats, SNI resulted in sustained and robust increased hippocampal IL-1β expression, which was only transient in rats with CCI. In this strain, IL-6 expression was not affected in any of the 2 injury models and IL-1ra expression was significantly increased in rats with SNI or CCI at late phases. We found that the degree and development of neuropathic pain depend on the specific nerve injury model and rat strain; that hippocampal IL-1β mRNA levels correlate with neuropathic pain behavior; that, in contrast to sham-operated animals, there are no correlations between hippocampal IL-1β and IL-1ra or IL-6 in neuropathic rats; and that alterations in cytokine expression are restricted to the hippocampus contralateral to the injury side, again implying that the observed changes reflect nociception.

Original languageEnglish (US)
Pages (from-to)2827-2835
Number of pages9
Issue number12
StatePublished - Dec 2011


  • Cytokines
  • Hippocampus
  • IL-1
  • IL-1ra
  • Lateralization
  • Neuropathic pain

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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