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| In pediatric cough management, neuromodulators act on specific pathways, including sensory nerves and the cough reflex arc, offering potential for targeted therapies. This review aims to examine the rationale for using neuromodulators in the management of cough in children. |
| What Are Neuromodulators? |
| Neuromodulators are endogenous chemicals that regulate neurons or synapses in the nervous system. Unlike neurotransmitters that induce direct responses at the synapse, neuromodulators modify intrinsic neuronal properties, synaptic transmission strength, and overall circuit dynamics. Examples include monoamines (dopamine, serotonin), neuropeptides (substance P, oxytocin), and cytokines. |
| Neuromodulator Drugs |
 |
| The major classes of neuromodulators for cough in pediatrics. |
|
| Pharmacological Neuromodulators |
| Drug |
How It Works |
Efficacy |
Safety |
Dextromethorphan
(DXM) |
Modulates the central cough reflex by binding to NMDA receptors and other key brain sites. |
Reduced total coughs by 21.0% and daytime cough frequency by 25.5%; no effect on nighttime cough. |
Generally well-tolerated but not recommended by the American Academy of Pediatrics or the ACCP. |
| Levodropropizine |
Targets peripheral sensory nerves, inhibiting neuropeptides like substance P and bradykinin. |
Effectively reduces cough frequency and severity in children and adolescents with acute post-viral cough. |
Well-tolerated with minimal side effects. |
| Local Anesthetics (e.g., Lidocaine) |
Blocks voltage-gated sodium channels on sensory nerve fibers, reducing excitability. |
Significant reduction in sufentanil-induced cough (SIC) severity in pediatric studies. |
Serum levels >5 mg/L can cause tremors, hallucinations, and cardiac complications. |
| H1 Antihistamines (e.g., Loratadine) |
Blocks histamine H1 receptors, reducing allergic inflammation and cough reflex sensitivity. |
| • |
Loratadine: Reduced ocular/nasal symptoms and cough frequency in allergic cough and rhinoconjunctivitis. |
| • |
Montelukast + Loratadine/Budesonide: Effective in managing cough variant asthma, improving lung function and reducing inflammation. |
|
First-generation drugs cause sedation; second-generation drugs have a rare risk of QT prolongation. |
| loperastine |
Acts on the brainstem's cough center with antihistaminic properties. |
Significant reduction in nighttime cough frequency, improving sleep for children and caregivers (effective in children 2+ years old). |
Mild side effects like drowsiness and dry mouth. |
|
| Natural Neuromodulators |
Natural
Remedy |
How It Works |
Efficacy |
Safety |
| Honey |
Honey’s viscosity stimulates saliva production, reducing cough receptor sensitivity and suppressing the urge to cough. |
Clinical trials demonstrated significant reductions in cough severity and caregiver stress compared to diphenhydramine and placebo. A systematic review confirmed honey’s superiority over OTC cough suppressants. |
Safe for children over one year; contraindicated in infants due to the risk of botulism. |
| Ginger |
Contains bioactive compounds like gingerols that modulate inflammation and neural pathways. |
No pediatric-specific trials conducted. |
Limited safety data; not specifically recommended for pediatric use due to lack of evidence. |
| Licorice Root |
Bioactive compounds reduce cough reflex sensitivity and enhance mucus clearance. |
Studies in mice and combination therapies in pediatric asthma show reduced cough frequency and severity. |
The EMA advises against use in children under 18 due to limited safety data. |
| Thyme (Thymus vulgaris) |
Thymol and carvacrol reduce inflammation and modulate the cough reflex. |
RCTs in children with asthma exacerbations showed significant reductions in activity-induced cough and improved lung function (e.g., FEV1). |
Not recommended by EMA for children under 18 due to limited safety data. |
|
| Conclusion |
| Neuromodulators—both pharmacological and natural—offer a promising shift in pediatric cough care, addressing both acute and chronic cases. While honey emerges as the most supported natural remedy, drugs like levodropropizine lead the way among pharmacological options, offering superior efficacy and safety. |
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| GGI-CO-A1-AQS-300033085-DVC-B25-0246 |
| For the use of a Registered Medical Practitioner, Hospital or Laboratory only. |
| Reference: |
| Foti Randazzese S, Toscano F, Gambadauro A, et al. Neuromodulators in Acute and Chronic Cough in Children: An Update from the Literature. Int J Mol Sci. 2024;25(20):11229. Published 2024 Oct 18. doi:10.3390/ijms252011229. Click here to view the original article |
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