The role of corticotropin-releasing factor in pain and analgesia.

Corticotropin-releasing factor (CRF) is a peptide that is released from the hypothalamus and in widespread areas of the brain following exposure to stressors. It is considered to be a mediator of many of the effects of stress, and its analgesic properties have been demonstrated in many studies. However, for primarily methodological reasons, the effects of CRF in the central nervous system have been neglected whereas the peripheral effects of CRF have been overemphasized. We present evidence that: (1) CRF can act at all levels of the neuraxis to produce analgesia; (2) the release of beta-endorphin does not explain the analgesia following intravenous or intracranial CRF administration; (3) inflammation must be present for local CRF to evoke analgesia and (4) the analgesic effects of CRF show specificity for prolonged pain. These findings suggest that CRF may have a significant role in chronic pain syndromes associated with hypothalamic-pituitary-adrenal axis abnormalities. Furthermore, CRF may represent a new class of analgesics that merits further study. Implications for the relationship between stress and pain are discussed.