Combined laryngeal inflammation and trauma mediate long-lasting immunoreactivity response in the brainstem sensory nuclei in the rat

Abstract

Somatosensory feedback from the larynx plays a critical role in regulation of normal upper airway functions, such as breathing, deglutition, and voice production, while altered laryngeal sensory feedback is known to elicit a variety of pathological reflex responses, including persistent coughing, dysphonia, and laryngospasm. Despite its clinical impact, the central mechanisms underlying the development of pathological laryngeal responses remain poorly understood. We examined the effects of persistent vocal fold (VF) inflammation and trauma, as frequent causes of long-lasting modulation of laryngeal sensory feedback, on brainstem immunoreactivity in the rat. Combined VF inflammation and trauma were induced by injection of lipopolysaccharide (LPS) solution and compared to VF trauma alone from injection of vehicle solution and to controls without any VF manipulations. Using a c-fos marker, we found significantly increased Fos-like immunoreactivity (FLI) in the bilateral intermediate/parvicellular reticular formation (IRF/PCRF) with a trend in the left solitary tract nucleus (NTS) only in animals with combined LPS-induced VF inflammation and trauma. Further, FLI in the right NTS was significantly correlated with the severity of LPS-induced VF changes. However, increased brainstem FLI response was not associated with FLI changes in the first-order neurons of the laryngeal afferents located in the nodose and jugular ganglia in either group. Our data indicate that complex VF alterations (i.e., inflammation/trauma vs. trauma alone) may cause prolonged excitability of the brainstem nuclei receiving a direct sensory input from the larynx, which, in turn, may lead to (mal)plastic changes within the laryngeal central sensory control.

Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer

“…Persistent or uncontrolled pain can result from neuropathic sensory dysfunction. In the rat injury model, Simonyan et al [70] showed that acute inflammation and trauma to vocal folds can elicit immunoreactive effects to sensory nuclei in the brain stem. Thus, injuries to glottis could upregulate central sensory response, promoting long-term hyper-excitability.…”

Herbs for Voice Database: Developing a Rational Approach to the Study of Herbal Remedies Used in Voice Care

“…Laryngeal somatosensory feedback plays an important role in regulation of normal upper airway functions, like voice production, and altered sensory feedback from the larynx is known to be involved in a variety of pathological reflex responses including dysphonia. 18 Laryngeal sensory input alterations occur frequently and may be induced by laryngeal inflammation due to voice abuse, upper respiratory infection and irritation, vocal fold trauma and others. 19 Accordingly, the plants in Herbs for Voice Database are mostly used as remedies for irritation symptoms and infection effects and show mainly anti-inflammatory, analgesic, and antimicrobial activities.…”

Radiation-Related Dysphagia: From Pathophysiology to Clinical Aspects

“…Moreover, a pathophysiological neuromuscular vicious circle can be described regarding postradiation dysphagia mechanism mainly consisting in a selective loss of the more radiosensitive type IIb myofibers together with a damage of peripheral nerves that innervate the swallowing musculature [29,34,35]. In the early phase (during and immediately after radiotherapy), the neuropathic radiation damage usually arises from the breakdown of epithelium lining of pharyngolaryngeal mucosa, triggering a cascade of inflammatory mediators (i.e., cytokines, neuropeptides, and glutamate signals) that cause significant pain and discomfort and result in persistent sensory deficit [36,37]. In the late phase (after months from radiotherapy), the replacement of muscular fibers with fibrotic tissue, characterized by loss of vascularity and matrix disorganization that disrupts well-defined compartmentalized structures as well as excessive collagen deposit that entraps nerve trunks or alters the vascular network between or within the nerve tracts, leads to muscular and neurological deficits [38,39].…”