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

Abstract

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 CRF 9-41 (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 CRF9-41 in three different doses or injected with α-helical CRF 9-41 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 CRF 9-41 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 CRF 9-41 did not cause any modification on the index of analgesia in the hot plate test but did reduce innate fear behavior [1].

Corticotropin-Releasing Factor Mediates Pain-Induced Anxiety through the ERK1/2 Signaling Cascade in Locus Coeruleus Neurons

“…Similarly, we did not find a significant effect of the α-CRF antagonist in control noninflamed animals. Overall, the effects in the ipsilateral paw and on anxiety-like behavior in MA rats are consistent with studies showing that administration of the α-helical CRF receptor antagonist to the basolateral or central nuclei of the amygdala has no effect on the nociceptive threshold but that it reduced innate fear behavior ( Donatti and Leite-Panissi, 2013 ). Nevertheless, the lack of changes in nociception might be related to the use of a broad-spectrum CRF antagonist that blocks nonspecifically the signaling of CRF1 and CRF2 receptors.…”

Avaliação da sensibilidade nociceptiva e do comportamento emocional após estresse agudo e crônico em ratos com inflamação persistente nas ATMs e o possível envolvimento de receptores para CRF

“…Corroborando essas afirmações, estudo de Ji e Neugebauer (2008) utilizando baixas concentrações de CRF (0,01 a 1 µM) no CEA, as quais levam a ativação de receptores CRF 1, verificou efeitos facilitatórios na dor, enquanto que altas concentrações de CRF (10 µM) causam ativação de receptores CRF 2 levando aos efeitos inibitórios na dor. Da mesma forma, estudo prévio de nosso laboratório em que se verificou o efeito da administração de CRF no CEA e no núcleo basolateral da amígdala (BLA) demonstrou que na dose de 1,0 µg/0,2 µL ocorreu aumento do IAPQ (DONATTI e LEITE-PANISSI, 2013) No presente trabalho a administração de 1,0 µg/0,2 µL de agonista CRF no CEA promoveu aumento do IAPQ, entretanto, não podemos afirmar se por ativação de receptores CRF 1 ou CRF 2 , desde que o CRF tem atuação em ambos receptores.. Os mecanismos facilitatórios e inibitórios ainda necessitam de maiores investigações para serem completamente entendidos, mas acredita-se que o efeito da ativação de receptores CRF será determinado pela relativa dominância entre esses mecanismos opostos. Estudo de Ji e Neugebauer (2008) demonstrou que administração de alta concentração de CRF (10 µM) no CEA produziu inibição da resposta eletrofisiológica de neurônios dessa região após a estimulação nociva da articulação do joelho de ratos.…”