Corticotropin-Releasing Factor in the Brain and Blocking Spinal Descending Signals Induce Hyperalgesia in the Latent Sensitization Model of Chronic Pain

Latent sensitization is a model of chronic pain in which an injury triggers a period of hyperalgesia followed by an apparent recovery, but in which pain sensitization persists but is suppressed by opioid and adrenergic receptors. One important characteristic of latent sensitization is that hyperalgesia can be triggered by acute stress. To determine whether the effect of stress is mimicked by the activation of corticotropin-releasing factor (CRF) signaling in the brain, rats with latent sensitization induced by injecting complete Freund's adjuvant (CFA, 50 μl) in one hind paw were given an intracerebroventricular (i.c.v.) injection of CRF. The i.c.v. injection of CRF (0.6 μg, 10 μl), but not saline, induced bilateral mechanical hyperalgesia in rats with latent sensitization. In contrast, CRF i.c.v. did not induce hyperalgesia in rats without latent sensitization (injected with saline in the hind paw). To determine whether descending pain inhibition mediates the suppression of hyperalgesia in latent sensitization, rats with CFA-induced latent sensitization received an intrathecal injection of lidocaine (10%, 1 μl) at the cervical-thoracic spinal cord to produce a spinal block. Lidocaine-injected rats, but not rats injected intrathecally with saline, developed bilateral mechanical hyperalgesia. Intrathecal lidocaine did not induce hyperalgesia in rats without latent sensitization (injected with saline in the hind paw). These results show that i.c.v. CRF mimicked the hyperalgesic response triggered by stress during latent sensitization, possibly by blocking inhibitory spinal descending signals that suppress hyperalgesia.