A neuroanatomical framework for the central modulation of respiratory sensory processing and cough by the periaqueductal grey

McGovern, Alice E; Ajayi, Itopa E.; Farrell, Michael J.; Mazzone, Stuart B.

doi:10.21037/jtd.2017.08.119

Cited by 19 publications

(13 citation statements)

References 85 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is salient to note that increasing pack-years was associated with increases in thresholds to detect an urge-to-cough (i.e. less sensitivity), which supports speculation that midbrain and brainstem responses could contribute to decreased sensitivity to capsaicin challenge among smokers and may be an adaptive response in chronic coughers [7,17,37] in attempts to suppress persistent airway inputs.…”

Section: Evidence For Altered Central Inhibitory Network Activity In Smokersmentioning

confidence: 58%

Altered neural activity in brain cough suppression networks in cigarette smokers

2019

Self Cite

View full text Add to dashboard Cite

Cough is important for airway defence, and studies in healthy animals and humans have revealed multiple brain networks intimately involved in the perception of airway irritation, cough induction and cough suppression. Changes in cough sensitivity and/or the ability to suppress cough accompany pulmonary pathologies, suggesting a level of plasticity is possible in these central neural circuits. However, little is known about how persistent inputs from the lung might modify the brain processes regulating cough.In the present study, we used human functional brain imaging to investigate the central neural responses that accompany an altered cough sensitivity in cigarette smokers.In nonsmokers, inhalation of the airway irritant capsaicin induced a transient urge-to-cough associated with the activation of a distributed brain network that included sensory, prefrontal and motor cortical regions. Cigarette smokers demonstrated significantly higher thresholds for capsaicin-induced urge-to-cough, consistent with a reduced sensitivity to airway irritation. Intriguingly, this was accompanied by increased activation in brain regions known to be involved in both cough sensory processing (primary sensorimotor cortex) and cough suppression (dorsolateral prefrontal cortex and the midbrain nucleus cuneiformis). Activations in the prefrontal cortex were highest among participants with the least severe smoking behaviour, whereas those in the midbrain correlated with more severe smoking behaviour.These outcomes suggest that smoking-induced sensitisation of central cough neural circuits is offset by concurrently enhanced central suppression. Furthermore, central suppression mechanisms may evolve with the severity of smoke exposure, changing from initial prefrontal inhibition to more primitive midbrain processes as exposure increases.

show abstract

Section: Evidence For Altered Central Inhibitory Network Activity In Smokersmentioning

confidence: 58%

Altered neural activity in brain cough suppression networks in cigarette smokers

2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, several regions of the brain that may regulate cough sensitivity were identified by functional magnetic resonance imaging studies ( Ando et al., 2016 ; Bautista et al., 2019 ). Patients with cough hypersensitivity exhibited an elevated neural activity in the lateral/ventrolateral periaqueductal gray (l/vlPAG) and nucleus of the solitary tract (NTS) when exposed to nebulized capsaicin ( Ando et al., 2016 ; McGovern et al., 2017 ). In addition, it has been found that the l/vlPAG is involved in controlling the respiratory functions and that electric stimulation of periaqueductal gray decreases coughing reflexes ( Faull et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, it has been found that the l/vlPAG is involved in controlling the respiratory functions and that electric stimulation of periaqueductal gray decreases coughing reflexes ( Faull et al., 2019 ). It has been shown that l/vlPAG subpopulations and their descending pathways are critical for itch and pain processing ( Gao et al., 2019 ; Samineni et al., 2017 , 2019 ; Liu et al., 2019 ), the anatomical basis and molecular mechanisms of which are similar to that of cough processing to a certain degree, given that they can all be mediated by small-diameter sensory C-fibers, TRP (transient receptor potential) superfamily ionotropic receptors and inflammatory mediators ( Lavinka and Dong, 2013 ; McGovern et al., 2017 ; Pecova et al., 2020 ). Activation of l/vlPAG GABAergic neurons suppresses itch but facilitates pain behaviors, whereas inhibition of these neurons results in enhanced itch and decreased pain behaviors, indicating that these neurons play a role in gating itch processing and promoting pain processing ( Samineni et al., 2017 , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to the l/vlPAG, the NTS might also be involved in the modulation of cough sensitivity ( Mazzone et al., 2015 ; McGovern et al., 2017 ; Singh et al., 2020 ). The NTS receives projections from nodose sensory neurons, which primarily innervate the intrapulmonary airways ( Mazzone and Undem, 2016 ; McGovern et al., 2015a ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A descending pathway emanating from the periaqueductal gray mediates the development of cough-like hypersensitivity

et al. 2022

View full text Add to dashboard Cite

Summary Chronic cough is a common refractory symptom of various respiratory diseases. However, the neural mechanisms that modulate the cough sensitivity and mediate chronic cough remain elusive. Here, we report that GABAergic neurons in the lateral/ventrolateral periaqueductal gray (l/vlPAG) suppress cough processing via a descending pathway. We found that l/vlPAG neurons are activated by coughing-like behaviors and that tussive agent-evoked coughing-like behaviors are impaired after activation of l/vlPAG neurons. In addition, we showed that l/vlPAG neurons form inhibitory synapses with the nucleus of the solitary tract (NTS) neurons. The synaptic strength of these inhibitory projections is weaker in cough hypersensitivity model mice than in naïve mice. Important, activation of l/vlPAG GABAergic neurons projecting to the NTS decreases coughing-like behaviors. In contrast, suppressing these neurons enhances cough sensitivity. These results support the notion that l/vlPAG GABAergic neurons play important roles in cough hypersensitivity and chronic cough through disinhibition of cough processing at the medullary level.

show abstract

“…There is still quite a debate as to the potential mechanisms of action of nonpharmacological interventions for refractory chronic cough. Patients with refractory chronic cough have been shown to have increased peripheral and central sensitisation of the cough reflex as well as decreased descending inhibitory control of their cough (Ando et al 2016, McGovern et al 2017, Mazzone and Undem 2016.…”

Section: Mechanisms Of Action Of Non-pharmacological Interventionsmentioning

confidence: 99%

Non-pharmacological interventions for chronic cough: The past, present and future

Mitchell

Ellis

Ludlow³

et al. 2019

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

Non-pharmacological interventions have been explored in people with refractory chronic cough. Normally delivered by Physiotherapists and or Speech and Language Therapists, these interventions aim to educate patients about their cough, provide them with cough suppression techniques and breathing exercises, improve vocal/laryngeal hydration and psychoeducational counselling to help them gain greater control of their cough. Six key studies have been completed over the past 12 years that have consistently found non-pharmacological interventions help to improve quality of life and reduce cough frequency. Some studies also found improvements in cough reflex sensitivity and severity. Despite promising results there now needs to be further work to optimise these interventions. There is a need to standardise terminology used such as relabelling the intervention as cough control therapy and move away from uni-disciplinary terms. Standardised patient selection, including screening protocols, optimal timing and delivery of the interventions as well as the outcome measures used to evaluate interventions need further exploration.

show abstract

A neuroanatomical framework for the central modulation of respiratory sensory processing and cough by the periaqueductal grey

Cited by 19 publications

References 85 publications

Altered neural activity in brain cough suppression networks in cigarette smokers

Altered neural activity in brain cough suppression networks in cigarette smokers

A descending pathway emanating from the periaqueductal gray mediates the development of cough-like hypersensitivity

Non-pharmacological interventions for chronic cough: The past, present and future

Contact Info

Product

Resources

About