Insulin potentiates the response to capsaicin in dorsal root ganglion neurons in vitro and muscle afferents ex vivo in normal healthy rodents

Abstract

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What is behind the curtain? Revealing muscle metaboreceptor sensitization

“…However, it is noteworthy that findings by Hori et al. (2022) come from supra‐pathophysiological insulin levels under resting conditions, requiring attention when translating it to cardiorespiratory responses to exercise in patients with chronic hyperinsulinaemia.…”

“…Although Hori et al. (2022) have clearly shown TRPV1 insulin‐mediated responses, TRPV1 accounts for one among many known group IV afferent fibre receptors, such as acid‐sensing ion channels (ASIC), bradykinin B2 (Kinin B2) and purinergic receptor (P2X). Thus, it is plausible that the excitatory role of insulin on thin afferent fibres could not only arise from TRPV1 activation but also other receptors (e.g.…”

“…Indeed, as compared with healthy individuals, patients with type 2 diabetes have heightened sympathetic nerve and cardiovascular responses to isometric exercise and activation of metabolically sensitive afferent fibres via post-exercise circulatory occlusion (Grotle et al, 2020). However, it is noteworthy that findings by Hori et al (2022) come from supra-pathophysiological insulin levels under resting conditions, requiring attention when translating it to cardiorespiratory responses to exercise in patients with chronic hyperinsulinaemia.…”

“…One unresolved question is the modulatory role of circulating substances on the function of group III and IV fibres. To address this, Hori et al (2022) investigated the effect of insulin on transient receptor potential vanilloid 1 (TRPV1) responsiveness to capsaicin at small dorsal root ganglion (DRG) neurons (in vitro) and action potentials in group IV muscle afferents of normal healthy rodents (ex vivo). Additionally, the authors tested the insulin effect on renal sympathetic nerve activity (RSNA) and arterial blood pressure of decerebrated rats during capsaicin-induced TRPV1 activation (in vivo).…”

“…However, the exact neuronal receptors and pathways by which these and other modulatory substances act are poorly understood -they are likely highly complex and will require multiple well-designed studies to reveal. Therefore, although Hori et al (2022) and others have advanced the understanding of mechanisms underlying pathophysiological responses to exercise, this topic will continue to be pertinent for years to come.…”