Experimental neuropathy increases limbic forebrain CRF

Eur J Pain. 2012 Jan;16(1):61-71. doi: 10.1016/j.ejpain.2011.05.016.


Neuropathic pain is often accompanied by stress, anxiety and depression. Although there is evidence for involvement of corticotropin-releasing factor (CRF), the detailed neuronal basis of these pain-related mood alterations is unknown. This study shows that peripheral mononeuropathy was accompanied by changes in limbic forebrain CRF, but did not lead to changes in the functioning of the hypothalamo-pituitary-adrenal axis and the midbrain Edinger-Westphal centrally projecting (EWcp) neuron population, which play main roles in the organism's response to acute pain. Twenty-four days after chronic constriction injury (CCI) of the rat sciatic nerve, the oval bed nucleus of the stria terminalis (BSTov) contained substantially more Crf mRNA as did the central amygdala (CeA), which, in addition, possessed more CRF. In contrast, Crf mRNA and CRF contents of the hypothalamic paraventricular nucleus (PVN) were unaffected by CCI. Similarly, EWcp neurons, producing the CRF family member urocortin 1 (Ucn1) and constitutively activated by various stressors including acute pain, did not show an effect of CCI on Ucn1 mRNA or Ucn1. Also, the immediate early gene products cFos and deltaFosB in the EWcp were unaffected by CCI. These results indicate that neuropathic pain does not act via the HPA-axis or the EWcp, but includes a main role of Crf in the limbic system, which is in clear contrast to stressors like acute and chronic pain, which primarily act on the PVN and the EWcp.

MeSH terms

  • Amygdala / metabolism
  • Amygdala / pathology
  • Animals
  • Body Weight / physiology
  • Constriction, Pathologic / metabolism
  • Constriction, Pathologic / pathology
  • Corticotropin-Releasing Hormone / metabolism*
  • Hyperalgesia / metabolism
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • In Situ Hybridization
  • Limbic System / metabolism*
  • Limbic System / pathology
  • Male
  • Neuralgia / metabolism*
  • Neuralgia / pathology
  • Pain Measurement
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Neuropathy / metabolism
  • Sciatic Neuropathy / pathology
  • Septal Nuclei / metabolism
  • Septal Nuclei / pathology
  • Tissue Fixation
  • Urocortins / biosynthesis
  • Urocortins / genetics
  • Weight Gain / physiology


  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Urocortins
  • Corticotropin-Releasing Hormone