Amiloride modulation of carbon dioxide hypersensitivity and thermal nociceptive hypersensitivity induced by interference with early maternal environment

Battaglia, Marco; Rossignol, Orlane; Bachand, Karine; D’Amato, Francesca R.

doi:10.1177/0269881118784872

Cited by 18 publications

(38 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A clinical implication of the environmental covariation is that some early‐life adversities (You, Albu, Lisenbardt, & Meagher, 2018) could increase liability to both anxiety and pain. Preclinical, genetically‐informed models of co‐occurring anxiety, pain, and early‐life adversities are beginning to provide leads about etiological mechanisms including gene‐environment interplay (Cittaro et al, 2016; Giannese et al, 2018), and new somatic treatments (Battaglia, Rossignol, Bachand, D'Amato, & De Koninck, 2019) that may constitute alternatives to current conceptualizations and treatments.…”

Section: Discussionmentioning

confidence: 99%

Trajectories of pain and anxiety in a longitudinal cohort of adolescent twins

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Trajectories of pain and anxiety in a longitudinal cohort of adolescent twins

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…In a series of comparative human and preclinical studies of responses to CO 2 (an unconditioned stimulus that evokes panic-like responses in humans at risk for panic disorder and hyperventilation in rodents) [5][6][7][8][9][10], we reported that life adversities enhance the liability to anxiety and pain through the enrichment of acid-sensing ion channel (ASIC) genes -1 and -2 [11][12][13]. Coherent with these findings, ASIC-antagonist amiloride normalizes the enhanced anxious and nociceptive responses that are proper of mice exposed to early disrupted maternal care and the nociceptive responses of rats that underwent prenatal maternal stress [12,14]. In a series of randomized human clinical trials, amiloride was shown to be safe and effective in humans for the treatment of cystic fibrosis following inhalational administration [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Stability of extemporaneously compounded amiloride nasal spray

et al. 2020

Self Cite

View full text Add to dashboard Cite

Anxiety disorders (AD) are the most common mental conditions affecting an estimated 40 million adults in the United States. Amiloride, a diuretic agent, has shown efficacy in reducing anxious responses in preclinical models by inhibiting the acid-sensing ion channels (ASIC). By delivering amiloride via nasal route, rapid onset of action can be achieved due to direct "nose-to-brain" access. Therefore, this study reports the formulation, physical, chemical, and microbiological stability of an extemporaneously prepared amiloride 2 mg/mL nasal spray. The amiloride nasal spray was prepared by adding 100 mg of amiloride hydrochloride to 50 mL of sterile water for injection in a sterile reagent bottle. A stability-indicating high-performance liquid chromatography (HPLC) method was developed and validated. Forceddegradation studies were performed to confirm the ability of the HPLC method to identify the degradation products from amiloride distinctively. The physical stability of the amiloride nasal spray was assessed by pH, clarity, and viscosity assessments. For chemical stability studies, samples of nasal sprays stored at room temperature were collected at time-points 0, 3 hr., 24 hr., and 7 days and were assayed in triplicate using the stability-indicating HPLC method. Microbiological stability of the nasal spray solution was evaluated for up to 7 days based on the sterility test outlined in United States Pharmacopoeia (USP) chapter 71. The stability-indicating HPLC method identified the degradation products of amiloride without interference from amiloride. All tested solutions retained over 90% of the initial amiloride concentration for the 7-day study period. There were no changes in color, pH, and viscosity in any sample. The nasal spray solutions were sterile for up to 7 days in all samples tested. An extemporaneously prepared nasal spray solution of amiloride hydrochloride (2 mg/mL) was physically, chemically, and microbiologically stable for 7 days when stored at room temperature.

show abstract

“…This is a combined chemoreceptive/nociceptive stress-induced molecular modification that has been observed in the medulla oblongata where the protection centers around the response to CO 2 -induced cerebral acidosis that leads to ACIS1-protective modification in respiration and nociception. Where epigenetically predisposed GAD and panic disorders are correlated with elevated CO 2 levels as induced in utero or as the result of ELF-associated choking or suffocation, the blockade of the ACIS1 gene with amiloride may be considered as a potential pharmacotherapeutic intervention [29]. The key point derived from this study is that environmental stress induces a neuroepigenomic response that may instantiate pCO 2 levels and reconditioning toward psychiatric conditions (e.g., GAD) in adults.…”

Section: Epigenetics Of the Early Uterine Environment And Potential Fmentioning

confidence: 94%

“…Such early life adversities (ELFs) as maternal stress during pregnancy have been correlated to both anxiety disorders and the potential for the experience of pain throughout life. A recent paper has linked animal model carbon dioxide exposure and subsequent hypersensitivity to ELF-associated anxiety [29]. In this study, mice were cross-fostered in an atmosphere enriched to 6% CO 2 in the presence or absence of an acid channel ion sensing 1 gene (ACIS1) blockade drug called amiloride.…”

Section: Epigenetics Of the Early Uterine Environment And Potential Fmentioning

confidence: 99%

The Diaeventology of Anxiety Disorders

Guerra¹

2019

Anxiety Disorders - From Childhood to Adulthood

View full text Add to dashboard Cite

Anxiety is a crippling neuropsychiatric condition that encompasses a complex endophenotypic network of genetic, immunological, epigenetic, and metabolic mechanisms, interacting with the environment. A new approach to complex biological systems, including mental states and their neurological correlates, is diaeventology, a paradigm that exposes the event ontologies of these biomolecular/cellular mechanisms. General anxiety disorder has been studied in subclinical and clinical research settings where evidence is obtained for a longitudinal patterning of chronic and episodic and often increasingly stressful life events that provide the etiology and development of the pathology. Early events that involve brain oxygen deprivation coupled with carbon dioxide abundance are linked to biochemical and epigenetic processes associated with anxiety instantiation. A verified analysis of the current evidence suggests a neuroimmune mechanism that aligns with stress pathophysiology and epigenetic re-tailoring of key genomic loci that inappropriately compensate and misdirect biological defense mechanisms toward central nervous system dysfunction presenting as anxiety disorders.

show abstract

Amiloride modulation of carbon dioxide hypersensitivity and thermal nociceptive hypersensitivity induced by interference with early maternal environment

Cited by 18 publications

References 57 publications

Trajectories of pain and anxiety in a longitudinal cohort of adolescent twins

Trajectories of pain and anxiety in a longitudinal cohort of adolescent twins

Stability of extemporaneously compounded amiloride nasal spray

The Diaeventology of Anxiety Disorders

Contact Info

Product

Resources

About