Activation of the corticotropin-releasing factor receptor from the basolateral or central amygdala modulates nociception in guinea pigs

Corticotropin-releasing factor (CRF) is a peptide that is released from the hypothalamus into widespread areas of the brain. Evidence has suggested that CRF is involved as a neuromodulator outside of the hypothalamic-pituitary-adrenal axis, playing an important role in fear, anxiety, depression and pain modulation. Our previous report demonstrated that CRF receptor activation in basolateral (BLA) or central nuclei of the amygdala (CeA) produces innate fear in guinea pigs. Inhibition of these receptors via administration of α-helical CRF9-41 (a nonspecific antagonist) into the CeA or BLA decreased innate fear behavior [1]. Additionally, there is strong evidence that emotional behavior and nociception can be modulated simultaneously. The present study was conducted to investigate the involvement of the CRF receptors of the BLA or CeA in nociception in guinea pigs. Guinea pigs were treated with CRF and α-helical CRF>9-41> in three different doses or injected with α-helical CRF9-41 preceded by CRF into the BLA or CeA, and they were evaluated using the hot plate test. Our findings indicated that activation of CRF receptors in the BLA and in the CeA promoted antinociception, and this effect was reversed by preadministration of α-helical CRF9-41 in the same area. The treatment with α-helical CRF>9-41> per se into the BLA and CeA did not alter nociception. Thus, nociception modulation occurs in a phasic manner, whereas defensive behavior can occur tonically because the α-helical CRF9-41 did not cause any modification on the index of analgesia in the hot plate test but did reduce innate fear behavior [1].