scholarly journals Insulin sensitizes neural and vascular TRPV1 receptors in the trigeminovascular system

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Judit Rosta ◽  
Máté Tóth ◽  
Nadine Friedrich ◽  
Péter Sántha ◽  
Gábor Jancsó ◽  
...  

Abstract Background Clinical observations suggest that hyperinsulinemia and insulin resistance can be associated with migraine headache. In the present study we examined the effect of insulin on transient receptor potential vanilloid 1 (TRPV1) receptor-dependent meningeal nociceptor functions in rats. Methods The effects of insulin on the TRPV1 receptor stimulation-induced release of calcitonin gene related peptide (CGRP) from trigeminal afferents and changes in meningeal blood flow were studied. Colocalization of the insulin receptor, the TRPV1 receptor and CGRP was also analyzed in trigeminal ganglion neurons. Results Insulin induced release of CGRP from meningeal afferents and consequent increases in dural blood flow through the activation of TRPV1 receptors of trigeminal afferents. Insulin sensitized both neural and vascular TRPV1 receptors making them more susceptible to the receptor agonist capsaicin. Immunohistochemistry revealed colocalization of the insulin receptor with the TRPV1 receptor and CGRP in a significant proportion of trigeminal ganglion neurons. Conclusions Insulin may activate or sensitize meningeal nociceptors that may lead to enhanced headache susceptibility in persons with increased plasma insulin concentration.

2007 ◽  
Vol 86 (9) ◽  
pp. 898-902 ◽  
Author(s):  
H.Y. Li ◽  
C.-K. Park ◽  
S.J. Jung ◽  
S.-Y. Choi ◽  
S.J. Lee ◽  
...  

Eugenol, a natural capsaicin congener, is widely used in dentistry. Eugenol inhibits voltage-activated Na+ and Ca2+ channels in a transient receptor potential vanilloid 1 (TRPV1)-independent manner. We hypothesized that eugenol also inhibits voltage-gated K+ currents, and investigated this in rat trigeminal ganglion neurons and in a heterologous system using whole-cell patch clamping. Eugenol inhibited voltage-gated K+ currents, and the inhibitory effects of eugenol were observed in both capsaicin-sensitive and capsaicin-insensitive neurons. Pre-treatment with capsazepine, a well-known antagonist of TRPV1, failed to block the inhibitory effects of eugenol on K+ currents, suggesting no involvement of TRPV1. Eugenol inhibited human Kv1.5 currents stably expressed in Ltk− cells, where TRPV1 is not endogenously expressed. We conclude that eugenol inhibits voltage-gated K+ currents in a TRPV1-independent manner. The inhibition of voltage-gated K+ currents is likely to contribute to the irritable action of eugenol. Abbreviations: human Kv1.5 channel, hKv1.5; transient receptor potential vanilloid 1, TRPV1.


2017 ◽  
Author(s):  
Benoit Michot ◽  
Caroline Lee ◽  
Eugene Podborits ◽  
Jennifer L. Gibbs

AbstractSensory neurons innervating the dental pulp have unique morphological and functional characteristics compared to neurons innervating other tissues. Stimulation of dental pulp afferents whatever the modality or intensity of the stimulus, even light mechanical stimulation that would not activate nociceptors in other tissues, produces an intense pain. These specific sensory characteristics could involve receptors of the Transient Receptor Potential channels (TRP) family. In this study, we evaluated 1) the expression of TRPA1 and TRPM8 receptors in trigeminal ganglion neurons innervating the dental pulp compared to sensory neurons innervating the oral mucosa or the skin of the face, and 2) the involvement of these receptors in dental pulp sensitivity to cold stimulation. We showed a similar expression of TRPM8 and CGRP in sensory neurons innervating the dental pulp, the skin or the buccal mucosa. On the contrary, TRPA1 was expressed in a higher proportion of neurons innervating the mucosa (43%) than in neurons innervating the dental pulp (19%) or the skin (24%). Moreover, neurons innervating the dental pulp had a higher proportion of large neurons (24%) compared to neurons innervating the skin (8%) or the mucosa (10%). The evaluation of trigeminal ganglion neuron sensitivity to TRPM8 agonist, TRPA1 agonist and cold stimulation, showed that a significant proportion of neurons innervating the skin (10%) or the mucosa (37%) were sensitive to cold stimulation but insensitive to TRPM8 and TRPA1 activation. Similarly, the application of a cold stimulation on the tooth induced an overexpression of cFos in the trigeminal nucleus that was not prevented by administration of a TRPA1 antagonist or the genetic deletion of TRPM8. However, the pretreatment with the local anesthetic carbocaine abolish the cold-induced cFos overexpression. In conclusion, the unique sensory characteristics of the dental pulp would be independent to TRPA1 and TRPM8 expression and functionality.


2017 ◽  
Vol 16 (1) ◽  
pp. 167-167
Author(s):  
B.E. Cairns ◽  
J. Liu ◽  
H. Wong

Abstract Aims In temporomandibular disorders sufferers, muscle pain is more severe in individuals who have undergone a traumatic stress. Why stress exacerbates masticatory muscle pain in these individuals is not known. One possibility is that under conditions of stress there is an interaction between the sympathetic and sensory nervous systems. This study investigated whether trigeminal ganglion neurons that innervate the masseter muscle express α1 adrenergic receptor subtypes to identify whether a direct interaction between the sympathetic and sensory nervous systems is feasible. Methods Masseter muscle ganglion neurons were identified by injection of the fluorescent dye fast blue into the masseter muscle of 4 Sprague Dawley rats (2 male, 2 female). Trigeminal ganglion sections were stained for α1a, α1b or α1d adrenergic receptors, as well as the transient receptor potential vanilloid 1 (TrpV1) receptor. Sections were examined with a Leica confocal microscope. The percent of masseter ganglion neurons expressing each receptor was calculated. Results Masseter muscle ganglion neurons expressed α1a(29 ± 9%), α1b (34 ± 4%) and α1d (19 ± 13%) adrenergic receptors. Expression of all three α1 receptor subtypes was higher in female rats than in male rats. Expression of α1b receptors was more commonly found on larger diameter masseter ganglion neurons. Overall 11±3% of masseter ganglion neurons expressed the TrpV1 receptor, which suggests they served a nociceptive function. The TrpV1 receptor was co-expressed by about ~10% of α1a and α1b receptor positive masseter ganglion neurons. Conclusions Afferent fibers that innervate the masseter muscle express all three α1 adrenergic receptor subtypes. Agonists at the α1 receptor have been previously shown to depolarize trigeminal ganglion neurons, which suggests that activation of these receptors on masseter muscle afferents would be excitatory. The expression of α1 receptors by putative nociceptors that innervate the masseter may permit a direct interaction between the sensory and sympathetic system that contributes to pain in this muscle.


PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e77998 ◽  
Author(s):  
Matthias Lübbert ◽  
Jessica Kyereme ◽  
Nicole Schöbel ◽  
Leopoldo Beltrán ◽  
Christian Horst Wetzel ◽  
...  

2017 ◽  
pp. 549-552 ◽  
Author(s):  
N. KALYNOVSKA ◽  
P. ADAMEK ◽  
J. PALECEK

Transient receptor potential vanilloid type 1 (TRPV1) receptors are important in the development of different pathological chronic pain states. Here we examined the role of spinal cord TRPV1 receptors in the mechanisms leading to activation of dorsal horn neurons after paclitaxel (PAC) treatment. PAC is a widely used chemotherapeutic drug that often leads to development of painful neuropathy. Immunohistochemical analysis of c-Fos protein expression in dorsal horn neurons was used as a marker of neuronal activation. Rat spinal cord slices were processed for in vitro incubation with PAC (100 nM) and TRPV1 receptor antagonists (SB366791 and AMG9810; 10 µM). PAC treatment induced significant upregulation of c-Fos nuclear expression in superficial dorsal horn neurons that was diminished by TRPV1 receptor antagonists pre-incubation. These results further substantiated the role of spinal TRPV1 receptors in the development of paclitaxel-induced neuropathic pain and contribute to better understanding of the pathological mechanisms involved.


2008 ◽  
pp. S69-S77
Author(s):  
D Špicarová ◽  
J Paleček

Transient receptor potential vanilloid 1 (TRPV1) receptor is a nonselective cation channel activated by capsaicin, a pungent substance from chili peppers. It is considered to act as an integrator of various physical and chemical nociceptive stimuli, as it can be gated by noxious heat (>43 oC), low pH (protons) and also by recently described endogenous lipids. The structure and function of TRPV1 receptors was vigorously studied, especially since its cloning in 1997. However, most of the research was pointed towards the role of TRPV1 receptors in the peripheral tissues. Mounting evidence now suggests that TRPV1 receptors on the central branches of dorsal root ganglion neurons in the spinal cord may play an important role in modulation of pain and nociceptive transmission. The aim of this short review was to summarize the knowledge about TRPV1 receptors in the spinal cord dorsal horn, preferentially from morphological and electrophysiological studies on spinal cord slices and from in vivo experiments.


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