scholarly journals TRPV1 (Transient Receptor Potential Vanilloid 1) Sensitization of Skeletal Muscle Afferents in Type 2 Diabetic Rats With Hyperglycemia

Author(s):  
Rie Ishizawa ◽  
Han-Kyul Kim ◽  
Norio Hotta ◽  
Gary A. Iwamoto ◽  
Jere H. Mitchell ◽  
...  

The blood pressure response to exercise is exaggerated in type 2 diabetes (T2D). However, the underlying mechanisms remain unclear. It is hypothesized that one mechanism mediating the potentiated cardiovascular response in T2D is the sensitization of chemically sensitive afferent neurons by activation of metaboreceptors. To test this hypothesis, we examined TRPV1 (transient receptor potential vanilloid 1)-induced cardiovascular responses in vivo and muscle afferent discharge ex vivo in T2D rats. Additionally, TRPV1 and PKC (protein kinase C) protein levels in dorsal root ganglia subserving skeletal muscle were assessed. For 14 to 16 weeks, Sprague-Dawley rats were given either a normal diet (control) or a high-fat diet in combination with a low dose (35 and 25 mg/kg) of streptozotocin (T2D). Administration of capsaicin, TRPV1 agonist, in hindlimb evoked significantly greater increases in mean arterial pressure and renal sympathetic nerve activity in decerebrated T2D than control. In a muscle-nerve preparation, the discharge to capsaicin exposure in group IV afferents isolated from T2D was likewise significantly augmented at a magnitude that was proportional to glucose concentration. Moreover, the discharge to capsaicin was potentiated by acute exposure of group IV afferents to a high-glucose environment. T2D showed significantly increased phospholyrated-TRPV1 and -PKCα levels in dorsal root ganglia neurons as compared with control. These findings suggest that group IV muscle afferents are sensitized by PKC-induced TRPV1 overactivity in early stage T2D with hyperglycemia and, thereby, may contribute to the potentiated circulatory response to TRPV1 activation in the disease.

2021 ◽  
Vol 12 ◽  
Author(s):  
Omar Páez ◽  
Pedro Segura-Chama ◽  
Angélica Almanza ◽  
Francisco Pellicer ◽  
Francisco Mercado

Pain by chemical irritants is one of the less well-described aspects of nociception. The acidic substance is the paradigm of the chemical noxious compound. An acidic insult on cutaneous, subcutaneous and muscle tissue results in pain sensation. Acid (or H+) has at least two main receptor channels in dorsal root ganglia (DRG) nociceptors: the heat receptor transient receptor potential vanilloid 1 (TRPV1) and the acid-sensing ionic channels (ASICs). TRPV1 is a low-sensitivity H+ receptor, whereas ASIC channels display a higher H+ sensitivity of at least one order of magnitude. In this review, we first describe the functional and structural characteristics of these and other H+-receptor candidates and the biophysics of their responses to low pH. Additionally, we compile reports of the expression of these H+-receptors (and other possible complementary proteins) within the DRG and compare these data with mRNA expression profiles from single-cell sequencing datasets for ASIC3, ASIC1, transient receptor potential Ankiryn subtype 1 (TRPA1) and TRPV1. We show that few nociceptor subpopulations (discriminated by unbiased classifications) combine acid-sensitive channels. This comparative review is presented in light of the accumulating evidence for labeled-line coding for most noxious sensory stimuli.


2021 ◽  
Author(s):  
Elena Conte ◽  
Adele Romano ◽  
Michela De Bellis ◽  
Maria Luisa De Ceglia ◽  
Maria Rosaria Carratù ◽  
...  

We explored the involvement of Oxytocin receptor (Oxtr)/ Transient-receptor-potential-vanilloid-1 (TRPV1) genes and Oxytocin (Oxt) on the adaptation of skeletal muscle to cold stress challenge in mice. Oxtr expression in hypothalamic paraventricular (PVN), supraoptic nuclei (SON), and hippocampus (HIPP) were evaluated by immunohistochemistry in parallel with the measurement of circulating Oxt. The Oxtr and TRPV1 gene expression in Soleus (SOL) and Tibialis Anterior (TA) muscles were investigated by RT-PCR. Histological studies of the cardiac muscle after cold stress were also performed. Male mice (n=15) were divided into controls maintained at room temperature (RT=24°C), exposed to cold stress (CS) at T=4°C for 6 hours (6h), and 5 days (5d). Immunohistochemical studies showed that Oxtr protein expression increased by 2-fold (p=0.01) in PVN and by 1.5-fold (p=0.0001) in HIPP after 6h and 5d CS, but decreased by 2-fold (p=0.026) in SON at 5d. Both Oxtr and TRPV1 gene expression increased after 6h and 5d CS in SOL and TA muscles. Oxtr vs TRPV1 gene expression in SOL and TA muscles evaluated by regression analysis was linearly correlated following CS at 6h and 5d but not at control temperature of 24+1°C, supporting the hypothesis of coupling between these genes. The circulating levels of Oxt are unaffected after 6h CS but decreased by 0.2-fold (p=0.0141) after 5d CS. This is the first report that Oxtr and TRPV1 expression are upregulated in response to cold acclimation in skeletal muscle. The up-regulation of Oxtr in PVN and HIPP balances the decrease of circulating Oxt.


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