T1429 Protease Activated Receptor 2 Sensitizes Transient Receptor Potential Vanilloid 4 On Mouse Colonic Dorsal Root Ganglia Neurons

2008 ◽  
Vol 134 (4) ◽  
pp. A-554
Author(s):  
Francisco Bautista-Cruz ◽  
Nigel W. Bunnett ◽  
Stephen J. Vanner
2017 ◽  
Vol 127 (4) ◽  
pp. 695-708 ◽  
Author(s):  
Daisuke Sugiyama ◽  
Sinyoung Kang ◽  
Nicholas Arpey ◽  
Preeyaphan Arunakul ◽  
Yuriy M. Usachev ◽  
...  

Abstract Background H2O2 has a variety of actions in skin wounds but has been rarely studied in deep muscle tissue. Based on response to the transient receptor potential ankyrin 1 antagonists after plantar incision, we hypothesized that H2O2 exerts nociceptive effects via the transient receptor potential ankyrin 1 in muscle. Methods Nociceptive behaviors in rats (n = 269) and mice (n = 16) were evaluated after various concentrations and volumes of H2O2 were injected into the gastrocnemius muscle or subcutaneous tissue. The effects of H2O2 on in vivo spinal dorsal horn neuronal activity and lumbar dorsal root ganglia neurons in vitro were evaluated from 26 rats and 6 mice. Results Intramuscular (mean ± SD: 1,436 ± 513 s) but not subcutaneous (40 ± 58 s) injection of H2O2 (100 mM, 0.6 ml) increased nociceptive time. Conditioned place aversion was evident after intramuscular (–143 ± 81 s) but not subcutaneous (–2 ± 111 s) injection of H2O2. These H2O2-induced behaviors were blocked by transient receptor potential ankyrin 1 antagonists. Intramuscular injection of H2O2 caused sustained in vivo activity of dorsal horn neurons, and H2O2 activated a subset of dorsal root ganglia neurons in vitro. Capsaicin nerve block decreased guarding after plantar incision and reduced nociceptive time after intramuscular H2O2. Nociceptive time after intramuscular H2O2 in transient receptor potential ankyrin 1 knockout mice was shorter (173 ± 156 s) compared with wild-type mice (931 ± 629 s). Conclusions The greater response of muscle tissue to H2O2 may help explain why incision that includes deep muscle but not skin incision alone produces spontaneous activity in nociceptive pathways.


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.


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.


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