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Cutaneous neurturin overexpression alters mechanical, thermal, and cold responsiveness in physiologically identified primary afferents.

ABSTRACT: Neurotrophic factors play an important role in the regulation of functional properties of sensory neurons under normal and pathological conditions. The GDNF family member neurturin is one such factor that has been linked to modulating responsiveness to peripheral stimuli. Neurturin binds to the GFR?2 receptor, a receptor found primarily in isolectin B4-expressing polymodal cutaneous nociceptors. Previous work has shown that knockout of GFR?2 alters heat, but not mechanical, responses in dissociated sensory neurons and reduces pain-related behaviors during the second phase of the formalin test. Research has also shown that overexpression of neurturin in basal keratinocytes increases behavioral responsiveness to mechanical stimulation and innocuous cooling of the skin without affecting noxious heat responses. Here we directly examined the impact of neurturin overexpression on cutaneous afferent function. We compared physiological responses of individual sensory neurons to mechanical and thermal stimulation of the skin, using an ex vivo skin-nerve-dorsal root ganglion-spinal cord preparation produced from neurturin-overexpressing (NRTN/OE) mice and wild-type littermate controls. We found that neurturin overexpression increases responsiveness to innocuous mechanical stimuli in A-fiber nociceptors, alters thermal responses in the polymodal subpopulation of C-fiber sensory neurons, and changes the relative numbers of mechanically sensitive but thermally insensitive C-fiber afferents. These results demonstrate the potential roles of different functional groups of sensory neurons in the behavioral changes observed in mice overexpressing cutaneous neurturin and highlight the importance of neurturin in regulating cutaneous afferent response properties.NEW & NOTEWORTHY GDNF family neurotrophic factors regulate the development and function of primary sensory neurons. Of these, neurturin has been shown to modulate mechanical and cooling sensitivity behaviorally. Here we show that overexpression of neurturin in basal keratinocytes regulates mechanical responsiveness in A-fiber primary sensory neurons while increasing the overall numbers of cold-sensing units. Results demonstrate a crucial role for cutaneous neurturin in modulating responsiveness to peripheral stimuli at the level of the primary afferent.

SUBMITTER: Jankowski MP

PROVIDER: S-EPMC5349329 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Cutaneous neurturin overexpression alters mechanical, thermal, and cold responsiveness in physiologically identified primary afferents.

Jankowski Michael P MP Baumbauer Kyle M KM Wang Ting T Albers Kathryn M KM Davis Brian M BM Koerber H Richard HR

Journal of neurophysiology 20161228 3

Neurotrophic factors play an important role in the regulation of functional properties of sensory neurons under normal and pathological conditions. The GDNF family member neurturin is one such factor that has been linked to modulating responsiveness to peripheral stimuli. Neurturin binds to the GFRα2 receptor, a receptor found primarily in isolectin B<sub>4</sub>-expressing polymodal cutaneous nociceptors. Previous work has shown that knockout of GFRα2 alters heat, but not mechanical, responses ...[more]

PMID: 28031403

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Project description:Thermal taste is a phenomenon whereby some individuals, known as thermal tasters (TT) experience taste sensations when their tongue is warmed or cooled. It was first reported in 2000 by Cruz and Green [1] and since then, most research has focused on comparing TT to thermal non-tasters (TnT; individuals who do not experience thermally-elicited sensations). As TT rate the intensity of taste stimuli higher than TnT, understanding the nature of this difference may help inform how individual differences in taste perception impact consumer liking and consumption of food and beverages. However, as the mechanism(s) underlying thermal tasting are yet to be fully elucidated, it is unclear if TT should be considered a homogeneous group or if subgroups exist. We created a dataset to help determine if the orosensory advantage is universal across all TT, or if it is mainly attributable to one or more subgroups of TT. To this end, the thermal taste screening data of 297 TT from 12 previous recruitment drives ('cohorts') was combined. This created the largest dataset of TT reported to date in a single study, allowing for an in-depth analysis of the differences between TT. After training on appropriate scale use, participants were familiarized with common taste and chemesthetic stimuli (sweet, sour, salty, bitter, umami, astringent and metallic). Using a sip-and-spit protocol, participants rinsed with the stimuli and rated the maximum intensity each stimulus elicited on a generalized Visual Analogue Scale (gVAS) or a generalized Labeled Magnitude Scale (gLMS). To account for minor methodological differences between the cohorts, ratings from each cohort were first converted to z-scores before being combined into the overall dataset. Next, participants underwent a series of 12 trials that assessed response to a thermal elicitation device during which each combination of two temperature regimes (warming and cooling) and three lingual sites (tongue tip, 1 cm to left, 1 cm to the right) were examined in duplicate. Participants were asked to rate the maximum intensity of any sensations experienced during each trial. TT were classified into subgroups based on the type of thermally-elicited taste reported (typically sweet, sour, salty, bitter, metallic), the temperature regime during which the sensation was elicited (warming or cooling) and the location on the tongue tested at which the sensation was experienced. Figures are provided that show the mean intensity ratings of aqueous solutions of chemical stimuli and corresponding standard errors for each of the TT subgroups. In addition, the TT Subgroup Naming Conventions provided should allow for a consistent and clear use of terminology across future thermal taste research. Readers are referred to Homogeneity of thermal tasters and implications for mechanisms and classification[2] for a full discussion of how these findings inform our understanding of the mechanism(s) underlying thermal taste and the practical implications of methodological differences in determining thermal taste status.

Dataset Information

Cutaneous neurturin overexpression alters mechanical, thermal, and cold responsiveness in physiologically identified primary afferents.

Publications

Cutaneous neurturin overexpression alters mechanical, thermal, and cold responsiveness in physiologically identified primary afferents.

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