Limbic and HPA axis function in an animal model of chronic neuropathic pain

Physiol Behav. 2006 Jun 15;88(1-2):67-76. doi: 10.1016/j.physbeh.2006.03.012. Epub 2006 May 2.


Chronic pain can be considered a form of chronic stress, and chronic pain patients often have disturbances of the hypothalamic-pituitary-adrenal (HPA) axis, including abnormal cortisol levels. In addition, chronic pain patients have an increased incidence of depression and anxiety, stress-related disorders that are frequently accompanied by disturbances in the limbic system (e.g. hippocampus and amygdala) and the HPA axis. Despite the fact that the literature supports a strong link between chronic pain, stress disorders, and limbic dysfunction, the mechanisms underlying the effects of chronic pain on the HPA axis and limbic system are not understood. The current study employs a rodent neuropathic pain model (chronic constriction injury (CCI) of the sciatic nerve) to assess the long-term impact of chronic pain on the HPA axis and limbic system. Adult male rats received CCI or sham surgery; nociceptive behavioral testing confirmed CCI-induced neuropathic pain. Tests of HPA axis function at 13-23 days postsurgery demonstrated that CCI did not affect indices of basal or restraint stress-induced HPA axis activity. CCI increased the expression of corticotrophin releasing hormone mRNA in the central amygdala, and not the paraventricular nucleus of the hypothalamus or the bed nucleus of the stria terminalis. Moreover, glucocorticoid receptor mRNA expression in CCI rats was increased in the medial and central amygdala, unaffected in the paraventricular nucleus, and decreased in the hippocampus. These results suggest that increased nociceptive sensitivity during chronic pain is associated with alterations in the limbic system, but is dissociated from HPA axis activation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Autoradiography / methods
  • Behavior, Animal
  • Body Weight / physiology
  • Chronic Disease
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation / physiology
  • Glucocorticoids / blood
  • Hypothalamo-Hypophyseal System / physiopathology*
  • In Situ Hybridization / methods
  • Limbic System / physiopathology*
  • Male
  • Pain Measurement / methods
  • Pituitary-Adrenal System / physiopathology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Sciatica / blood
  • Sciatica / physiopathology*
  • Time Factors


  • Glucocorticoids
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone