Русский 
English Corticotropin-releasing factor (CRF) as a mediator of pain response to stressor: involvement of CRF receptors of subtype 2, opioid receptors and glucocorticoid receptors in CRF-induced analgesic effect in rats
Background
Corticotropin-releasing factor (CRF) is expressed throughout the central nervous system and in peripheral tissues and coordinates a wide range of stress-induced response. Analgesia is one of the characteristics of stress reaction and CRF is involved in providing of stress-induced analgesia (SIA). Exogenous CRF produces analgesic effect in animals and humans. Periaqueductal gray matter of the midbrain (PAGM) plays a key role in generation of SIA. СRF action is mediated by CRF receptors of subtype 1 and 2 (CRF-R1 and CRF-R2 receptors). Both CRF-R1 and CRF-R2 are expressed within PAGM. CRF through CRF-R1 stimulates the ACTH/β endorphin release and, ACTH, in turn, stimulates glucocorticoid production.
Aims
The aim of the study was to investigate the involvement of CRF-R1 and CRF-R2 receptors and opioid and glucocorticoid receptors in analgesic effect caused by central or peripheral CRF administration in conscious rats.
Methods
CRF was administered intra-PAGM (0.7 mkg/rat) or intraperitoneally (40 mkg/kg). The involvement of CRF-R1 and CRF-R2 receptors, opioid receptors and glucocorticoid receptors was studied by antagonists of these receptors: NBI 27914, astressin2 β, naltrexone and RU 38486, respectively. The antagonists were administered centrally or peripherally before CRF injection. Somatic pain sensitivity was evaluated by tail flick latency (tail flick test). The experiments were performed according to the Declaration of Helsinki.
Results
Both peripheral and central CRF administration caused an increase in tail flick latencies (analgesic effect). CRF-induced analgesia was accompanied by an elevation of plasma corticosterone levels. Peripheral administration of NBI 271914 (5 mg/kg, i.p.), astressin2 β (200 mkg/kg, s.c.), naltrexone (1 mg/kg, i.p.) or RU 38486 (20 mg/kg, s.c.) attenuated the analgesia caused by peripheral CRF. In addition, RU 38486 or NBI 271914 by itself led to inhibition of somatic pain sensitivity. Intra-PAGM (1 mkg/rat) administration of naltrexone or astressin2 β attenuated the central as well as peripheral CRF-induced analgesia.
Conclusions
The data obtained suggest that CRF-R1 and CRF-R2, opioid receptors and glucocorticoid receptors are involved in CRF-induced analgesia and one of the mechanisms of CRF-induced analgesic effect on somatic pain sensitivity may be mediated through opioid and CRF-R2 receptors within PAGM. The study was supported by grant of Russian Science Foundation (RSF) № 19-15-00430.