Abstract
The corticotropin-releasing factor (CRF) is involved in somatic pain regulation and may produce an analgesic effect in humans and animals, although the mechanisms of the CRF-induced analgesia remain unclear. CRF action is mediated by the CRF receptors of subtypes 1 and 2 (CRF-R1 and CRF-R2, respectively). Activation of the hypothalamic –pituitary –adrenocortical axis (HPA) is provided by CRF-R1; but CRF-R2 are also involved in the regulation of the HPA axis, and, respectively, glucocorticoids, the end hormones of the HPA axis, also participate in somatic pain regulation. Additionally, opioids may contribute to the CRF-induced analgesia. This article serves as an overview of the role of CRF-R1 and CRF-R2, as well as glucocorticoid and opioid receptors in peripheral CRF-induced analgesia in conscious rats, while we focused on the data obtained under normal (non-pathological) conditions including results of our studies in rats. The involvement of CRF-R1 and CRF-R2, glucocorticoids and opioid receptors was studied under the same experimental conditions following pretreatment with appropriate antagonists: NBI 27914, astressin2-B, naltrexone and RU 38486, respectively. Somatic pain sensitivity was measured by the tail flick latencies induced by thermal stimulus (tail flick test). Peripheral administration of the CRF caused both an increase in the tail flick latencies (analgesic effect) and plasma corticosterone levels. Pretreatment with NBI 27914, astressin2-B, naltrexone or RU 38486 attenuated the peripheral CRF-induced analgesia. The results obtained suggest that the peripheral CRF-induced analgesic effect may be mediated through the involvement of CRF-R1 and CRF-R2 as well as opioid and glucocorticoid receptors, including CRF-R2 and opioid receptors within periaqueductal gray matter of the midbrain.
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Abbreviations
- CRF:
-
Corticotropin-releasing factor
- CRF-R1:
-
Corticotropin-releasing factor receptor of subtype 1
- CRF-R2:
-
Corticotropin-releasing factor receptor of subtype 2
- DRN:
-
Dorsal raphe nucleus
- GABA:
-
Gamma-aminobutyric acid
- GRs:
-
Glucocorticoid receptors
- HPA:
-
Hypothalamic –pituitary –adrenocortical axis
- 5-HT:
-
Serotonin
- LC:
-
Locus coeruleus
- MRs:
-
Mineralocorticoid receptors
- PAGM:
-
Periaqueductal gray matter of the midbrain
- SIA:
-
Stress-induced analgesia
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This study was supported by Russian Science Foundation (RSF) N 14-15-00790.
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Yarushkina, N.I., Filaretova, L.P. The peripheral corticotropin-releasing factor (CRF)-induced analgesic effect on somatic pain sensitivity in conscious rats: involving CRF, opioid and glucocorticoid receptors. Inflammopharmacol 26, 305–318 (2018). https://doi.org/10.1007/s10787-018-0445-5
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DOI: https://doi.org/10.1007/s10787-018-0445-5