The Role of Corticotropin-Releasing Hormone at Peripheral Nociceptors: Implications for Pain Modulation

Peripheral nociceptors and their synaptic partners utilize neuropeptides for signal transmission. Such communication tunes the excitatory and inhibitory function of nociceptor-based circuits, eventually contributing to pain modulation. Corticotropin-releasing hormone (CRH) is the initiator hormone for the conventional hypothalamic-pituitary-adrenal axis, preparing our body for stress insults. Although knowledge of the expression and functional profiles of CRH and its receptors and the outcomes of their interactions has been actively accumulating for many brain regions, those for nociceptors are still under gradual investigation. Currently, based on the evidence of their expressions in nociceptors and their neighboring components, several hypotheses for possible pain modulations are emerging. Here we overview the historical attention to CRH and its receptors on the peripheral nociception and the recent increases in information regarding their roles in tuning pain signals. We also briefly contemplate the possibility that the stress-response paradigm can be locally intrapolated into intercellular communication that is driven by nociceptor neurons. Such endeavors may contribute to a more precise view of local peptidergic mechanisms of peripheral pain modulation.

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Hypothalamic-pituitary-adrenal axis stress test in patients with early RA: role of corticotropin-releasing hormone promoter polymorphisms

Annals of the Rheumatic Diseases ◽

10.1136/ard.2011.151340 ◽

2011 ◽

Vol 70 (11) ◽

pp. 2058-2059 ◽

Cited By ~ 2

Author(s):

O. Malysheva ◽

U. Wagner ◽

M. Wahle ◽

M. Pierer ◽

U. Wagner ◽

...

Keyword(s):

Stress Test ◽

Hypothalamic Pituitary Adrenal Axis ◽

Corticotropin Releasing Hormone ◽

Promoter Polymorphisms ◽

Hypothalamic Pituitary Adrenal ◽

Releasing Hormone ◽

Adrenal Axis ◽

Early Ra ◽

Pituitary Adrenal Axis

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The role of the corticotropin-releasing hormone and its receptors in the regulation of stress response

Vavilov Journal of Genetics and Breeding ◽

10.18699/vj21.025 ◽

2021 ◽

Vol 25 (2) ◽

pp. 216-223

Author(s):

E. V. Sukhareva

Keyword(s):

Stress Response ◽

Mental Disorders ◽

Brain Regions ◽

Hypothalamic Nucleus ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone ◽

Brain Functions ◽

Increased Risk ◽

Mediator Systems

Stress is an essential part of everyday life. The neuropeptide corticotropin-releasing hormone (CRH, also called CRF and corticoliberin) plays a key role in the integration of neuroendocrine, autonomic and behavioral responses to stress. The activation of the hypothalamic-pituitary-adrenal axis (HPA axis) by neurons of the paraventricular hypothalamic nucleus (PVN), the primary site of synthesis CRH, triggers stress reactions. In addition to the hypothalamus, CRH is widespread in extrahypothalamic brain structures, where it functions as a neuromodulator for coordination and interaction between the humoral and behavioral aspects of a stress response. The axons of neurons expressing CRH are directed to various structures of the brain, where the neuropeptide interacts with specific receptors (CRHR1, CRHR2) and can affect various mediator systems that work together to transmit signals to different brain regions to cause many reactions to stress. Moreover, the effect of stress on brain functions varies from behavioral adaptation to increased survival and increased risk of developing mental disorders. Disturbances of the CRH system regulation are directly related to such disorders: mental pathologies (depression, anxiety, addictions), deviations of neuroendocrinological functions, inflammation, as well as the onset and development of neurodegenerative diseases such as Alzheimer’s disease. In addition, the role of CRH as a regulator of the neurons structure in the areas of the developing and mature brain has been established. To date, studies have been conducted in which CRHR1 is a target for antidepressants, which are, in fact, antagonists of this receptor. In this regard, the study of the participation of the CRH system and its receptors in negative effects on hormone-dependent systems, as well as the possibility of preventing them, is a promising task of modern physiological genetics. In this review, attention will be paid to the role of CRH in the regulation of response to stress, as well as to the involvement of extrahypothalamic CRH in pathophysiology and the correction of mental disorders.

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Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test

Acta Endocrinologica ◽

10.1530/eje.0.1420280 ◽

2000 ◽

Vol 142 (3) ◽

pp. 280-285 ◽

Cited By ~ 26

Author(s):

B Meczekalski ◽

A Tonetti ◽

P Monteleone ◽

F Bernardi ◽

S Luisi ◽

...

Keyword(s):

Body Weight ◽

Corticotropin Releasing Hormone ◽

Hypothalamic Amenorrhea ◽

Releasing Hormone ◽

Normal Body ◽

Adrenal Axis ◽

Normal Body Weight ◽

Cortisol Responses ◽

Pituitary Adrenal Axis

OBJECTIVE: Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. DESIGN: We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. METHODS: We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. RESULTS: Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). CONCLUSIONS: In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

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