Neuronal aldosterone elicits a distinct genomic response in pain signaling molecules contributing to inflammatory pain

Shaqura, Mohammed; Li, Li; Mohamed, Doaa M.; Li, Xiongjuan; Treskatsch, Sascha; Buhrmann, Constanze; Shakibaei, Mehdi; Beyer, Antje; Mousa, Shaaban A.; Schäfer, Michael

doi:10.1186/s12974-020-01864-8

Cited by 10 publications

(9 citation statements)

References 40 publications

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“…However, in CP/CPPS patients, higher NIH-CPSI total and pain domain scores (indicating worse symptom severity) were associated with greater aldosterone levels [ 64 ]. Prior mouse studies demonstrated that aldosterone production leads to hypersensitivity and likely contributes to pain signaling [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Hypertension and urologic chronic pelvic pain syndrome: An analysis of MAPP-I data

Conic,

Vasilopoulos,

Devulapally

et al. 2024

BMC Urol

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Background Urologic chronic pelvic pain syndrome (UCPPS), which includes interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis (CP/CPPS), is associated with increased voiding frequency, nocturia, and chronic pelvic pain. The cause of these diseases is unknown and likely involves many different mechanisms. Dysregulated renin-angiotensin-aldosterone-system (RAAS) signaling is a potential pathologic mechanism for IC/BPS and CP/CPPS. Many angiotensin receptor downstream signaling factors, including oxidative stress, fibrosis, mast cell recruitment, and increased inflammatory mediators, are present in the bladders of IC/BPS patients and prostates of CP/CPPS patients. Therefore, we aimed to test the hypothesis that UCPPS patients have dysregulated angiotensin signaling, resulting in increased hypertension compared to controls. Secondly, we evaluated symptom severity in patients with and without hypertension and antihypertensive medication use. Methods Data from UCPPS patients (n = 424), fibromyalgia or irritable bowel syndrome (positive controls, n = 200), and healthy controls (n = 415) were obtained from the NIDDK Multidisciplinary Approach to the Study of Chronic Pelvic Pain I (MAPP-I). Diagnosis of hypertension, current antihypertensive medications, pain severity, and urinary symptom severity were analyzed using chi-square test and t-test. Results The combination of diagnosis and antihypertensive medications use was highest in the UCPPS group (n = 74, 18%), followed by positive (n = 34, 17%) and healthy controls (n = 48, 12%, p = 0.04). There were no differences in symptom severity based on hypertension in UCPPS and CP/CPPS; however, IC/BPS had worse ICSI (p = 0.031), AUA-SI (p = 0.04), and BPI pain severity (0.02). Patients (n = 7) with a hypertension diagnosis not on antihypertensive medications reported the greatest severity of pain and urinary symptoms. Conclusion This pattern of findings suggests that there may be a relationship between hypertension and UCPPS. Treating hypertension among these patients may result in reduced pain and symptom severity. Further investigation on the relationship between hypertension, antihypertensive medication use, and UCPPS and the role of angiotensin signaling in UCPPS conditions is needed.

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Section: Discussionmentioning

confidence: 99%

Hypertension and urologic chronic pelvic pain syndrome: An analysis of MAPP-I data

Conic,

Vasilopoulos,

Devulapally

et al. 2024

BMC Urol

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“…The Western blot bands specific for CRF-R1 (56 kDa) or CRF-R2 (38 kDa) according to their data sheet were quantified by Java Image processing and analysis software (ImageJ, open-source image software downloaded from the web#) [ 30 , 31 ].…”

Section: Methodsmentioning

confidence: 99%

Functional and Anatomical Characterization of Corticotropin-Releasing Factor Receptor Subtypes of the Rat Spinal Cord Involved in Somatic Pain Relief

et al. 2021

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Corticotropin-releasing factor (CRF) orchestrates our body’s response to stressful stimuli. Pain is often stressful and counterbalanced by activation of CRF receptors along the nociceptive pathway, although the involvement of the CRF receptor subtypes 1 and/or 2 (CRF-R1 and CRF-R2, respectively) in CRF-induced analgesia remains controversial. Thus, the aim of the present study was to examine CRF-R1 and CRF-R2 expression within the spinal cord of rats with Freund’s complete adjuvant-induced unilateral inflammation of the hind paw using reverse transcriptase polymerase chain reaction, Western blot, radioligand binding, and immunofluorescence confocal analysis. Moreover, the antinociceptive effects of intrathecal (i.t.) CRF were measured by paw pressure algesiometer and their possible antagonism by selective antagonists for CRF-R1 and/or CRF-R2 as well as for opioid receptors. Our results demonstrated a preference for the expression of CRF-R2 over CRF-R1 mRNA, protein, binding sites and immunoreactivity in the dorsal horn of the rat spinal cord. Consistently, CRF as well as CRF-R2 agonists elicited potent dose-dependent antinociceptive effects which were antagonized by the i.t. CRF-R2 selective antagonist K41498, but not by the CRF-R1 selective antagonist NBI35965. In addition, i.t. applied opioid antagonist naloxone dose-dependently abolished the i.t. CRF- as well as CRF-R2 agonist-elicited inhibition of somatic pain. Importantly, double immunofluorescence confocal microscopy of the spinal dorsal horn showed CRF-R2 on enkephalin (ENK)-containing inhibitory interneurons in close opposition of incoming mu-opioid receptor-immunoreactive nociceptive neurons. CRF-R2 was, however, not seen on pre- or on postsynaptic sensory neurons of the spinal cord. Taken together, these findings suggest that i.t. CRF or CRF-R2 agonists inhibit somatic inflammatory pain predominantly through CRF-R2 receptors located on spinal enkephalinergic inhibitory interneurons which finally results in endogenous opioid-mediated pain inhibition.

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“…The Western blot bands speci c for CRF-R1 (56 kDa) or CRF-R2 (38 kDa) according to their data sheet were quanti ed by Java Image processing and analysis software (ImageJ, open-source image software downloaded from the web# [28,29].…”

Section: Western Blotmentioning

confidence: 99%

Functional and anatomical characterization of corticotropin-releasing factor receptor subtypes of the rat spinal cord involved in somatic pain relief

Mousa

Shaqura

Khalefa

et al. 2021

Preprint

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Corticotropin-releasing factor (CRF) orchestrates our body’s response to stressful stimuli. Pain is often stressful and counterbalanced by activation of CRF receptors along the nociceptive pathway although the involvement of the CRF receptor subtypes 1 and/or 2 (CRF-R1 and CRF-R2, respectively) in CRF-induced analgesia remains controversial. This study examined CRF-R1 and CRF-R2 expression within the spinal cord of rats with Freund’s complete adjuvant-induced hindpaw inflammation using reverse transcriptase polymerase chain reaction, Western blot, radioligand binding, and immunofluorescence confocal analysis. Moreover, paw pressure algesiometry examined antinociceptive effects of intrathecal (i.t.) CRF and their possible antagonism through CRF-R1 and/or CRF-R2 selective antagonists as well as the opioid receptor antagonist naloxone. Our results demonstrated predominantly CRF-R2 mRNA, protein, binding sites and immunoreactivity in the dorsal horn of the rat spinal cord. Consistently, CRF as well as CRF-R2 agonist elicited potent, dose-dependent anti-nociceptive effects which were antagonized selectively by i.t. CRF-R2 (K41498) antagonist but not by CRF-R1 (NBI35965) antagonist. Moreover, the opioid antagonist naloxone dose-dependently reversed the i.t. CRF- as well as CRF-R2 agonist-elicited inhibition of somatic pain. Supporting these findings, double immunofluorescence confocal microscopy showed CRF-R2 on enkephalin (ENK)-containing inhibitory interneurons in close opposition of incoming mu-opioid receptor-immunoreactive nociceptive neurons. CRF-R2 was, however, not seen on pre- or on postsynaptic sensory neurons of the spinal cord. Taken together, these findings suggest that i.t. CRF or CRF-R2 agonist inhibit inflammatory somatic pain, occurring predominantly through CRF-R2 receptors located on spinal enkephalinergic inhibitory interneurons, which results in endogenous opioid-mediated pain inhibition.

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Neuronal aldosterone elicits a distinct genomic response in pain signaling molecules contributing to inflammatory pain

Cited by 10 publications

References 40 publications

Hypertension and urologic chronic pelvic pain syndrome: An analysis of MAPP-I data

Hypertension and urologic chronic pelvic pain syndrome: An analysis of MAPP-I data

Functional and Anatomical Characterization of Corticotropin-Releasing Factor Receptor Subtypes of the Rat Spinal Cord Involved in Somatic Pain Relief

Functional and anatomical characterization of corticotropin-releasing factor receptor subtypes of the rat spinal cord involved in somatic pain relief

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