Experimental neuropathy increases limbic forebrain CRF

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 E dinger– W estphal 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 .