The vanilloid receptor-1 is expressed in rat spinal dorsal horn astrocytes

doi:10.1016/j.neulet.2003.12.051

Neuroscience Letters

Volume 357, Issue 2, 4 March 2004, Pages 123-126

https://doi.org/10.1016/j.neulet.2003.12.051 Get rights and content

Abstract

The vanilloid receptor-1 (TRPV1), expressed by nociceptive fibers, is a transducer of thermal and chemical nociceptive messages. However, endogenous ligands excite TRPV1 receptors localized on central nociceptive terminals and interneurons. Using immunocytochemistry at the ultrastructural level, we show that TRPV1 is also expressed in spinal glial cells characterized as astrocyte by double labeling with glial fibrillary acid protein. Quantification of the labeling shows that the most numerous labeling is neuronal and that 7% of the total TRPV1 labeling is localized in astrocytes. The total absence of staining in TRPV1 knock out mice strongly suggests that true TRPV1 protein is present in astrocytes. The localization of TRPV1-containing astrocytes apposed to nociceptive C-terminals suggests that they may be involved in the control of pain transmission.

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Cited by (81)

TRPV1: The key bridge in neuroimmune interactions
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The nervous and immune systems are crucial in fighting infections and inflammation and in maintaining immune homeostasis. The immune and nervous systems are independent, yet tightly integrated and coordinated organizations. Numerous molecules and receptors play key roles in enabling communication between the two systems. Transient receptor potential vanilloid subfamily member 1 (TRPV1) is a non-selective cation channel, recently shown to be widely expressed in the neuroimmune axis and implicated in neuropathic pain, autoimmune disorders, and immune cell function. TRPV1 is a key bridge in neuroimmune interactions, allowing for smooth and convenient communication between the two systems. Here, we discuss the coordinated cross-talking between the immune and nervous systems and the functional role and the functioning manner of the TRPV1 involved. We suggest that TRPV1 provides new insights into the collaborative relationship between the nervous and immune systems, highlighting exciting opportunities for advanced therapeutic approaches to treating neurogenic inflammation and immune-mediated diseases.
Pregabalin alleviates neuropathic pain via inhibition of the PKCε/TRPV1 pathway
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Pregabalin has been increasingly used in recent years, and becoming a first-line medication for the clinical treatment of neuropathic pain. However, the mechanisms underlying pregabalin-induced neuropathic pain alleviation remain unclear. In this study, we aimed to investigate whether PKC epsilon (PKCε)/ transient receptor potential vanilloid subtype 1(TRPV1) signaling pathway participated in pregabalin-induced analgesia during treatment of neuropathic pain using rat models of spared nerve injury (SNI). The left hind paw withdrawal mechanical thresholds (PWMT) of rats were measured preoperatively one day before and on day 1, 4, 7 and 14 after surgery. On day 7 after SNI surgery, the rats received ligation operation were administrated with pregabalin intraperitoneally and were intrathecally injected with PKC Inhibitor BIM Ⅰ or PKC agonist PMA for seven consecutive days, IL-1β and IL-6 expression levels in the spinal cord of rats were then assessed. Furthermore, we analyzed the PKCε, TRPV1, pTRPV1 and Glial fibrillary acidic protein (GFAP) protein levels and the expression of reactive astrocytes and the PKCε, TRPV1 and pTRPV1 positive cells on day 14 after SNI. Our findings indicated that pregabalin could relieve neuropathic pain to a certain extent by suppressing the PKCε/TRPV1 signaling pathway and inhibiting inflammatory processes in the spinal cord.
Peripherally administered cannabinoid receptor 2 (CB<inf>2</inf>R) agonists lose anti-allodynic effects in TRPV1 knockout mice, while intrathecal administration leads to anti-allodynia and reduced GFAP, CCL2 and TRPV1 expression in the dorsal spinal cord and DRG
2022, Brain Research
The transient receptor potential (TRP) superfamily of cation channels, of which the TRP vanilloid type 1 (TRPV1) receptor plays a critical role in inflammatory and neuropathic pain, is expressed on nociceptors and spinal cord dorsal horn neurons. TRPV1 is also expressed on spinal astrocytes and dorsal root ganglia (DRG) satellite cells. Agonists of the cannabinoid type 2 receptor (CB₂R) suppress allodynia, with some that can bind TRPV1. The neuroimmune C–C class chemokine-2 (CCL2) expressed on injured DRG nociceptor cell bodies, Schwann cells and spinal astrocytes, stimulates immune cell accumulation in DRG and spinal cord, a known critical element in chronic allodynia. The current report examined whether two CB₂R agonists, AM1710 and AM1241, previously shown to reverse light touch mechanical allodynia in rodent models of sciatic neuropathy, require TRPV1 activation that leads to receptor insensitivity resulting in reversal of allodynia. Global TRPV1 knockout (KO) mice with sciatic neuropathy given intrathecal or intraperitoneal AM1710 were examined for anti-allodynia followed by immunofluorescent microscopy analysis of lumbar spinal cord and DRG of astrocyte and CCL2 markers. Additionally, immunofluorescent analysis following intrathecal AM1710 and AM1241 in rat was performed. Data reveal that intrathecal AM1710 resulted in mouse anti-allodynia, reduced spinal astrocyte activation and CCL2 expression independent of TRPV1 gene deletion. Conversely, peripheral AM1710 in TRPV1-KO mice failed to reverse allodynia. In rat, intrathecal AM1710 and AM1241 reduced spinal and DRG TRPV1 expression, with CCL2-astrocyte and -microglial co-expression. These data support that CB₂R agonists can impact spinal and DRG TRPV1 expression critical for anti-allodynia.
Heat hypersensitivity is attenuated with altered expression level of spinal astrocytes after sciatic nerve injury in TRPV1 knockout mice
2021, Neuroscience Research
Citation Excerpt :
Increased cytokines, such as IL-1β, in spinal microglia and astrocytes after peripheral nerve injury directly affect TRPV1 (Kiguchi et al., 2012). TRPV1 which is co-expressed with astrocytes may be involved in the control of pain transmission in rats (Doly et al., 2004). We observed co-expression of TRPV1 and GFAP in the spinal dorsal horn, although the expression of TRPV1 in glial cells is still controversial (Marrone et al., 2017).
Transient receptor potential vanilloid 1 (TRPV1) modulates pain. Studies have indicated that TRPV1 is upregulated in the spinal dorsal horn in the neuropathic pain model, but its mechanism is unknown. Here, we examined the mechanism by which TRPV1 modulates neuropathic pain by employing partial sciatic nerve ligation (pSNL) in adult male C57BL/6 J (wild-type: WT) and TRPV1 knockout (Trpv1-/-) mice. We analyzed mechanical/heat sensitivities (von Frey test/hot plate test) and glial/neuronal activities (Iba-1/GFAP/FosB by immunofluorescence) in laminae I and II in the L5 ipsilateral dorsal horn of the spinal cord. Mechanical/heat sensitivities, expression levels of microglial Iba-1 and astrocytic GFAP, and the number of FosB-positive neurons were significantly increased on days 7 and 14 in the pSNL group compared with the sham-operated and non-operated groups of both WT and Trpv1-/- mice. While mechanical sensitivity was comparable between WT and Trpv1-/- mice, the threshold against heat sensitivity was markedly prolonged in Trpv1-/- than WT mice on day 14 after pSNL. Conversely, the increment of FosB positive neurons was significantly attenuated in Trpv1-/- than WT mice on days 7 and 14 after pSNL. These results suggest that TRPV1 may modulate thermal perception via increased astrocytes in the dorsal horn of the spinal cord.
Modulation of neuroinflammation: Role and therapeutic potential of TRPV1 in the neuro-immune axis
2017, Brain, Behavior, and Immunity
Citation Excerpt :
Miyake et al. discovered that TRPV1 functions on both the cytomembrane and the intracellular organelles, including the mitochondria, endoplasmic reticulum (ER), lysosomes, and golgi apparatus (Huang et al., 2010; Miyake et al., 2015); namely, the majority of TRPV1 is naturally expressed in microglia located in the endomembrane system rather than in the cytomembrane (Gallego-Sandin et al., 2009; Miyake et al., 2015). TRPV1 was also detected in astrocytes located in the spinal cord, retina, and other brain regions (Benito et al., 2012; Doly et al., 2004; Toth et al., 2005). By double-immunofluorescence-labeling with glial fibrillary acid protein (GFAP) and S100β at the ultrastructural level, it showed that 7% of the total TRPV1 labeling was localized in astrocytes (Doly et al., 2004) and was mainly distributed in the cell membrane/cytoplasm (Huang et al., 2010; Rycerz et al., 2016).
Transient receptor potential vanilloid type 1 channel (TRPV1), as a ligand-gated non-selective cation channel, has recently been demonstrated to have wide expression in the neuro-immune axis, where its multiple functions occur through regulation of both neuronal and non-neuronal activities. Growing evidence has suggested that TRPV1 is functionally expressed in glial cells, especially in the microglia and astrocytes. Glial cells perform immunological functions in response to pathophysiological challenges through pro-inflammatory or anti-inflammatory cytokines and chemokines in which TRPV1 is involved. Sustaining inflammation might mediate a positive feedback loop of neuroinflammation and exacerbate neurological disorders. Accumulating evidence has suggested that TRPV1 is closely related to immune responses and might be recognized as a molecular switch in the neuroinflammation of a majority of seizures and neurodegenerative diseases. In this review, we evidenced that inflammation modulates the expression and activity of TRPV1 in the central nervous system (CNS) and TRPV1 exerts reciprocal actions over neuroinflammatory processes. Together, the literature supports the hypothesis that TRPV1 may represent potential therapeutic targets in the neuro-immune axis.
Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function
2023, Acta Pharmacologica Sinica

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The vanilloid receptor-1 is expressed in rat spinal dorsal horn astrocytes

Abstract

Neuroscience

J. Urol.

Neurosci. Lett.

Trends Neurosci.

Anandamide regulates neuropeptide release from capsaicin-sensitive primary sensory neurons by activating both the cannabinoid 1 receptor and the vanilloid receptor 1 in vitro

Eur. J. Neurosci.

Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells

Proc. Natl. Acad. Sci. USA

Impaired nociception and pain sensation in mice lacking the capsaicin receptor

Science

The capsaicin receptor: a heat-activated ion channel in the pain pathway

Nature

Anandamide: some like it hot

Trends Pharmacol. Sci.