Electroacupuncture Reduces Cold Stress-Induced Pain through Microglial Inactivation and Transient Receptor Potential V1 in Mice

Receptor Potential ◽

Trpv1 Channel ◽

Thermal Pain ◽

Abstract Background Fibromyalgia pain lacks objective parameters to measure treatment efficacy. Fibromyalgia patients suffer from chronic and persistent widespread pain and generalized tenderness. Transient receptor potential V1 (TRPV1), which is reported as a Ca2+ permeable ion channel that can be activated by inflammation, is reported to be involved in the development of fibromyalgia pain. Methods The current study explored the transient receptor potential vanilloid 1 (TRPV1) channel functions as a noxious sensory input in mice cold stress model. It remains unknown whether electroacupuncture (EA) attenuates fibromyalgia pain or affects the TRPV1 pathway. Results We show that cold stress increases mechanical and thermal pain (Day 7: mechanical: 1.69 ± 0.41 g; thermal: 4.68 ± 0.56 s), and that EA and Trpv1 deletion counter this increase. EA and Trpv1 deletion reduced the cold stress-induced increase in inflammatory mediators and TRPV1-related molecules in the hypothalamus, periaqueductal gray (PAG), and cerebellum of mice. Conclusions Our results imply that EA has an analgesic effect associated with TRPV1 downregulation. We provide novel evidence that these inflammatory mediators can modulate the TRPV1 signaling pathway and suggest new potential therapeutic targets for fibromyalgia pain.

Electroacupuncture reduces cold stress-induced pain through microglial inactivation and transient receptor potential V1 in mice

Chinese Medicine ◽

10.1186/s13020-021-00451-0 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Hsien-Yin Liao ◽

Yi-Wen Lin

Keyword(s):

Cold Stress ◽

Inflammatory Mediators ◽

Sensory Input ◽

Receptor Potential ◽

Stress Model ◽

Widespread Pain ◽

Trpv1 Channel ◽

Thermal Pain ◽

Abstract Background The treatment, and efficacy thereof, is considered to be inadequate with specificity to alleviation of Fibromyalgia and its associated pain. Fibromyalgia patients suffer from chronic and persistent widespread pain and generalized tenderness. Transient receptor potential V1 (TRPV1), which is reported as a Ca2+ permeable ion channel that can be activated by inflammation, is reported to be involved in the development of fibromyalgia pain. Methods The current study explored the TRPV1 channel functions as a noxious sensory input in mice cold stress model. It remains unknown whether electroacupuncture (EA) attenuates fibromyalgia pain or affects the TRPV1 pathway. Results We show that cold stress increases mechanical and thermal pain (day 7: mechanical: 1.69 ± 0.41 g; thermal: 4.68 ± 0.56 s), and that EA and Trpv1 deletion counter this increase. EA and Trpv1 deletion reduced the cold stress-induced increase in inflammatory mediators and TRPV1-related molecules in the hypothalamus, periaqueductal gray (PAG), and cerebellum of mice. Conclusions Our results imply that EA has an analgesic effect associated with TRPV1 downregulation. We provide novel evidence that these inflammatory mediators can modulate the TRPV1 signaling pathway and suggest new potential therapeutic targets for fibromyalgia pain.

Faculty Opinions recommendation of The mechanosensitivity of mouse colon afferent fibers and their sensitization by inflammatory mediators require transient receptor potential vanilloid 1 and acid-sensing ion channel 3.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7001.464490 ◽

2006 ◽

Author(s):

Gyongyi Horvath

Keyword(s):

Ion Channel ◽

Inflammatory Mediators ◽

Receptor Potential ◽

Mouse Colon ◽

Afferent Fibers ◽

Streptozotocin-Induced Early Thermal Hyperalgesia is Independent of Glycemic State of Rats: Role of Transient Receptor Potential Vanilloid 1(TRPV1) and Inflammatory Mediators

Molecular Pain ◽

10.1186/1744-8069-7-52 ◽

2011 ◽

Vol 7 ◽

pp. 1744-8069-7-52 ◽

Cited By ~ 63

Author(s):

Mahendra Bishnoi ◽

Christine A Bosgraaf ◽

uvil Abooj ◽

Linlin Zhong ◽

Louis S Premkumar

Keyword(s):

Inflammatory Mediators ◽

Thermal Hyperalgesia ◽

Receptor Potential ◽

The Mechanosensitivity of Mouse Colon Afferent Fibers and Their Sensitization by Inflammatory Mediators Require Transient Receptor Potential Vanilloid 1 and Acid-Sensing Ion Channel 3

Journal of Neuroscience ◽

10.1523/jneurosci.0703-05.2005 ◽

2005 ◽

Vol 25 (47) ◽

pp. 10981-10989 ◽

Cited By ~ 303

Author(s):

R. C. W. Jones

Keyword(s):

Ion Channel ◽

Inflammatory Mediators ◽

Receptor Potential ◽

Mouse Colon ◽

Afferent Fibers ◽

Oxtr/TRPV1 expression and acclimation of skeletal muscle to cold-stress in male mice

Journal of Endocrinology ◽

10.1530/joe-20-0346 ◽

2021 ◽

Author(s):

Elena Conte ◽

Adele Romano ◽

Michela De Bellis ◽

Maria Luisa De Ceglia ◽

Maria Rosaria Carratù ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Cold Stress ◽

Receptor Potential ◽

Male Mice ◽

Transient Receptor ◽

Immunohistochemical Studies ◽

Circulating Levels

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.

Pore Helix Domain Is Critical to Camphor Sensitivity of Transient Receptor Potential Vanilloid 1 Channel

Anesthesiology ◽

10.1097/aln.0b013e318249cf62 ◽

2012 ◽

Vol 116 (4) ◽

pp. 903-917 ◽

Cited By ~ 9

Author(s):

Lenka Marsakova ◽

Filip Touska ◽

Jan Krusek ◽

Viktorie Vlachova

Keyword(s):

Spatial Distribution ◽

Plasma Membranes ◽

Receptor Potential ◽

Structural Basis ◽

Trpv1 Channel ◽

Patch Clamp Technique ◽

Trpv1 Channels ◽

Background The recent discovery that camphor activates and strongly desensitizes the capsaicin-sensitive and noxious heat-sensitive channel transient receptor potential vanilloid subfamily member 1 (TRPV1) has provided new insights and opened up new research paths toward understanding why this naturally occurring monoterpene is widely used in human medicine for its local counter-irritant, antipruritic, and anesthetic properties. However, the molecular basis for camphor sensitivity remains mostly unknown. The authors attempt to explore the nature of the activation pathways evoked by camphor and narrow down a putative interaction site at TRPV1. Methods The authors transiently expressed wild-type or specifically mutated recombinant TRPV1 channels in human embryonic kidney cells HEK293T and recorded cation currents with the whole cell, patch clamp technique. To monitor changes in the spatial distribution of phosphatidylinositol 4,5-bisphosphate, they used fluorescence resonance energy transfer measurements from cells transfected with the fluorescent protein-tagged pleckstrin homology domains of phospholipase C. Results The results revealed that camphor modulates TRPV1 channel through the outer pore helix domain by affecting its overall gating equilibrium. In addition, camphor, which generally is known to decrease the fluidity of cell plasma membranes, may also regulate the activity of TRPV1 by inducing changes in the spatial distribution of phosphatidylinositol-4,5-bisphosphate on the inner leaflet of the plasma membrane. Conclusions The findings of this study provide novel insights into the structural basis for the modulation of TRPV1 channel by camphor and may provide an explanation for the mechanism by which camphor modulates thermal sensation in vivo.

TRPV1: Structure, Endogenous Agonists, and Mechanisms

International Journal of Molecular Sciences ◽

10.3390/ijms21103421 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3421 ◽

Cited By ~ 2

Author(s):

Miguel Benítez-Angeles ◽

Sara Luz Morales-Lázaro ◽

Emmanuel Juárez-González ◽

Tamara Rosenbaum

Keyword(s):

Ion Channel ◽

Binding Sites ◽

Receptor Potential ◽

Trpv1 Channel ◽

Field Of Study ◽

Transient Receptor ◽

Shed Light ◽

Made In

The Transient Receptor Potential Vanilloid 1 (TRPV1) channel is a polymodal protein with functions widely linked to the generation of pain. Several agonists of exogenous and endogenous nature have been described for this ion channel. Nonetheless, detailed mechanisms and description of binding sites have been resolved only for a few endogenous agonists. This review focuses on summarizing discoveries made in this particular field of study and highlighting the fact that studying the molecular details of activation of the channel by different agonists can shed light on biophysical traits that had not been previously demonstrated.