Influence of acute and subchronic oral administration of dehydroepiandrosterone (DHEA) on nociceptive threshold in rats

Gąsińska, Emilia; Bujalska‐Zadrożny, Magdalena; Sar, M.; Makulska-Nowak, Helena E.

doi:10.1016/s1734-1140(12)70892-7

Cited by 9 publications

(6 citation statements)

References 21 publications

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“…In the fire fatality group, the significant β2-AR expression in the reticularis could be related to the modulation of the nociceptive function of DHEA and DHEAS [42,43], in particular in three of our subjects who died quickly from severe burns and, possibly, in intense painful conditions.…”

Section: Discussionmentioning

confidence: 99%

Post-Mortem Immunohistochemical Evidence of β2-Adrenergic Receptor Expression in the Adrenal Gland

Spagnolo

Mondello

Cardia

et al. 2019

IJMS

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The evidence from post-mortem biochemical studies conducted on cortisol and catecholamines suggest that analysis of the adrenal gland could provide useful information about its role in human pathophysiology and the stress response. Authors designed an immunohistochemical study on the expression of the adrenal β2-adrenergic receptor (β2-AR), a receptor with high-affinity for catecholamines, with the aim to show which zones it is expressed in and how its expression differs in relation to the cause of death. The immunohistochemical study was performed on adrenal glands obtained from 48 forensic autopsies of subjects that died as a result of different pathogenic mechanisms using a mouse monoclonal β2-AR antibody. The results show that immunoreactivity for β2-AR was observed in all adrenal zones. Furthermore, immunoreactivity for β2-AR has shown variation in the localization and intensity of different patterns in relation to the original cause of death. To the best of our knowledge, this is the first study that demonstrates β2-AR expression in the human cortex and provides suggestions on the possible involvement of β2-AR in human cortex hormonal stimulation. In conclusion, the authors provide a possible explanation for the observed differences in expression in relation to the cause of death.

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Section: Discussionmentioning

confidence: 99%

Post-Mortem Immunohistochemical Evidence of β2-Adrenergic Receptor Expression in the Adrenal Gland

Spagnolo

Mondello

Cardia

et al. 2019

IJMS

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“…Animal studies have shown that intrathecal treatment with bicuculline or picrotoxin, an antagonist of γ-aminobutyric acid type A receptor (GABA A -R), induces hyperalgesia [56], and the spinal application of muscimol (an agonist for GABA A -R) blocks NMDA-induced hyperalgesia [57]. Meanwhile, subchronic (5–14 days) administration of DHEA leads to an elevation in the nociceptive threshold for mechanical and thermal stimuli [27, 28] and induces a significant increase in GABA A -R δ-subunit mRNA transcription in the neurons of the ventral tegmental area [58]. In addition, a cell culture study showed that long-term treatment (72 h) with DHEA diminishes the basal transcriptional activity of glucocorticoid receptor (GR) [59].…”

Section: Discussionmentioning

confidence: 99%

The Involvement of the Hypothalamus-Pituitary-Adrenal Axis in the Development of Hyperalgesia during the Early Postoperative Period

Ahn

Park

et al. 2022

Neuroendocrinology

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Introduction: Hyperalgesia frequently occurs after surgery and is associated with adverse effects on surgical outcomes. Thus, we aimed to examine whether the hypothalamus-pituitary-adrenal (HPA) axis function after surgery is involved in the development of postoperative hyperalgesia. Methods: Surgery- and pain-related variables were measured 24 and 48 hours after the first and second total knee arthroplasties (TKAs) in postmenopausal patients undergoing one-week-interval staged bilateral TKA. Two sets of saliva samples were consecutively collected from patients before (pre-T1) and one week after (post-T1) the first TKA (n = 69). HPA axis function was analyzed in a subgroup of 20 patients with a typical cortisol awakening response (CAR) in both sets of saliva samples. Results: Surgery-related variables were comparable between the first and second TKAs. However, pain-related variables (pain ratings and the amount of opioid analgesics consumed) were greater after the second than the first TKA. Cortisol and dehydroepiandrosterone (DHEA) secretion during the post-awakening period (CARauc and Daucawk, respectively) was higher at post-T1 than at pre-T1, but the molar CARauc/Daucawk ratio was comparable between the time points examined. No relationship was observed between the pre-T1 CARauc and pain ratings after the first TKA. However, post-T1 CARauc showed a positive correlation with pain ratings after the second TKA. Postoperative pain ratings were negatively correlated with Daucawk and positively correlated with the molar CARauc/Daucawk ratio at all examined time points. Discussion/Conclusion: The results suggest that adrenocortical steroidogenic activity favoring the production of cortisol over DHEA after surgery may contribute to the development of hyperalgesia during the early postoperative period.

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“…Similar results have been observed with allopregnanolone, which has been shown to provide relief from thermal hyperalgesia evoked from diabetes in rats [ 43 ]. It is of note that intraperitoneal administration of DHEA increases the pain threshold in mice and rats [ 44 ]. The chronic analgesic effect of DHEA in that study was attributed to androgenic metabolites generated by the daily administration of DHEA, inducing a rapid pro-nociceptive action, while intrathecal administration of testosterone, an androgen deriving from DHEA, caused analgesia in neuropathic rats [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Analgesic and Anti-Inflammatory Effects of the Synthetic Neurosteroid Analogue BNN27 during CFA-Induced Hyperalgesia

et al. 2021

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Dehydroepiandrosterone (DHEA), an adrenal and neurosteroid hormone with strong neuroprotective and immunomodulatory properties, and ligand for all high-affinity neurotrophin tyrosine kinase receptors (Trk), also exerts important effects on hyperalgesia. Its synthetic, 17-spiro-epoxy analogue, BNN27, cannot be converted to estrogen or androgen as DHEA; it is a specific agonist of TrkA, the receptor of pain regulator Nerve Growth Factor (NGF), and it conserves the immunomodulatory properties of DHEA. Our study aimed to evaluate the anti-nociceptive and anti-inflammatory properties of BNN27 during Complete Freund’s Adjuvant (CFA)-induced inflammatory hyperalgesia in mice. Hyperalgesia was evaluated using the Hargreaves test. Inflammatory markers such as cytokines, NGF and opioids were measured, additionally to corticosterone and the protein kinase B (AKT) signaling pathway. We showed for the first time that treatment with BNN27 reversed hyperalgesia produced by CFA. The effect of BNN27 involved the inhibition of NGF in the dorsal root ganglia (DRG) and the increased synthesis of opioid peptides and their receptors in the inflamed paw. We also found alterations in the cytokine levels as well as in the phosphorylation of AKT2. Our findings strongly support that BNN27 represents a lead molecule for the development of analgesic and anti-inflammatory compounds with potential therapeutic applications in inflammatory hyperalgesia.

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Influence of acute and subchronic oral administration of dehydroepiandrosterone (DHEA) on nociceptive threshold in rats

Abstract: The results suggest that DHEA could be indicated as a drug to improve treatment of chronic pain disorders.

Cited by 9 publications

References 21 publications

Post-Mortem Immunohistochemical Evidence of β2-Adrenergic Receptor Expression in the Adrenal Gland

Post-Mortem Immunohistochemical Evidence of β2-Adrenergic Receptor Expression in the Adrenal Gland

The Involvement of the Hypothalamus-Pituitary-Adrenal Axis in the Development of Hyperalgesia during the Early Postoperative Period

Analgesic and Anti-Inflammatory Effects of the Synthetic Neurosteroid Analogue BNN27 during CFA-Induced Hyperalgesia

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