ABSTRACT
Clinical genetic studies have shown that loss of Nav1.7 function leads to the complete loss of acute pain perception. The global deletion is reported lethal in mice, however, and studies of mice with promoter-specific deletions of Nav1.7 have suggested that the role of Nav1.7 in pain transduction depends on the precise form of pain. We developed genetic and animal husbandry strategies that overcame the neonatal-lethal phenotype and enabled construction of a global Nav1.7 knockout mouse. Knockouts were anatomically normal, reached adulthood, and had phenotype wholly analogous to human congenital indifference to pain (CIP): compared to littermates, knockouts showed no defects in mechanical sensitivity or overall movement yet were completely insensitive to painful tactile, thermal, and chemical stimuli and were anosmic. Knockouts also showed no painful behaviors resulting from peripheral injection of nonselective sodium channel activators, did not develop complete Freund's adjuvant-induced thermal hyperalgesia, and were insensitive to intra-dermal histamine injection. Tetrodotoxin-sensitive sodium current recorded from cell bodies of isolated sensory neurons and the mechanically-evoked spiking of C-fibers in a skin-nerve preparation each were reduced but not eliminated in tissue from knockouts compared to littermates. Results support a role for Nav1.7 that is conserved between rodents and humans and suggest several possibly translatable biomarkers for the study of Nav1.7-targeted therapeutics. Results further suggest that Nav1.7 may retain its key role in persistent as well as acute forms of pain.
Subject(s)
NAV1.7 Voltage-Gated Sodium Channel/deficiency , Pain Insensitivity, Congenital/etiology , Animals , Disease Models, Animal , Female , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , NAV1.7 Voltage-Gated Sodium Channel/genetics , NAV1.7 Voltage-Gated Sodium Channel/physiology , Nerve Fibers, Unmyelinated/physiology , Nervous System/pathology , Nervous System/physiopathology , Olfaction Disorders/genetics , Olfaction Disorders/physiopathology , Pain Insensitivity, Congenital/genetics , Pain Insensitivity, Congenital/physiopathology , Pain Threshold/physiology , Phenotype , Sensory Receptor Cells/physiologyABSTRACT
OBJECTIVE: To investigate the characteristics and severity of swallowing difficulties among stroke patients with a tracheostomy tube, compared to those without. METHOD: A retrospective study was performed on two groups of 17 stroke patients with a tracheostomy tube (58.8 years) and without a tracheostomy tube (69.8 years) fed by Levine tube or a gastrostomy tube. There were no differences in the FIM (functional independence measure) score and brain lesions between the two groups. We evaluated the functional dysphagia scale (FDS) and aspiration; classified before, during, and after swallowing aspiration and silent aspiration. The swallowing task consisted of 2 ml of fluid and a videofluoroscopic swallowing study. RESULTS: There were no significant differences between the oral preparatory, oral and pharyngeal phase for the two groups in FDS. However, frequency of silent aspiration (p=0.007) and the total frequency of aspiration (p=0.038) were significantly higher in patients with tracheostomy. CONCLUSION: Patients with stroke who underwent tracheostomy showed no meaningful difference in FDS. However, there were significant differences in terms of silent aspiration and the total frequency of aspiration; caused by laryngopharyngeal desensitization and the anterior tethering effect on the tracheostomy tube. We have to pay more attention to the treatment and care of patients with tracheostomy tubes.
