Activation of transient receptor potential vanilloid 2-expressing primary afferents stimulates synaptic transmission in the deep dorsal horn of the rat spinal cord and elicits mechanical hyperalgesia

2014 ◽  
Vol 40 (8) ◽  
pp. 3189-3201 ◽  
Author(s):  
Hugues Petitjean ◽  
Sylvain Hugel ◽  
Florent Barthas ◽  
Yohann Bohren ◽  
Michel Barrot ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Dorsal Horn ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Primary Afferents ◽  
Mechanical Hyperalgesia ◽  
Transient Receptor Potential Vanilloid ◽  
Rat Spinal Cord ◽  
Transient Receptor

scholarly journals Paclitaxel Induces Upregulation of Transient Receptor Potential Vanilloid 1 Expression in the Rat Spinal Cord

2020 ◽  
Vol 21 (12) ◽  
pp. 4341 ◽  
Author(s):  
Yukako Kamata ◽  
Toshie Kambe ◽  
Terumasa Chiba ◽  
Ken Yamamoto ◽  
Kazuyoshi Kawakami ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Intrathecal Administration ◽  
Transient Receptor Potential Vanilloid ◽  
Rat Spinal Cord ◽  
Trpv1 Receptor ◽  
Transient Receptor

Painful peripheral neuropathy is a common adverse effect of paclitaxel (PTX) treatment. To analyze the contribution of transient receptor potential vanilloid 1 (TRPV1) in the development of PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia, TRPV1 expression in the rat spinal cord was analyzed after intraperitoneal administration of 2 and 4 mg/kg PTX. PTX treatment increased the expression of TRPV1 protein in the spinal cord. Immunohistochemistry showed that PTX (4 mg/kg) treatment increased TRPV1 protein expression in the superficial layers of the spinal dorsal horn 14 days after treatment. Behavioral assessment using the paw withdrawal response showed that PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia after 14 days was significantly inhibited by oral or intrathecal administration of the TRPV1 antagonist AMG9810. We found that intrathecal administration of small interfering RNA (siRNA) to knock down TRPV1 protein expression in the spinal cord significantly decreased PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia. Together, these results demonstrate that TRPV1 receptor expression in spinal cord contributes, at least in part, to the development of PTX-induced painful peripheral neuropathy. TRPV1 receptor antagonists may be useful in the prevention and treatment of PTX-induced peripheral neuropathic pain.

Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord

2015 ◽  
Vol 20 (10) ◽  
pp. 1337-1349 ◽  
Author(s):  
Morgana Duarte da Silva ◽  
Francisco José Cidral-Filho ◽  
Elisa Cristina Winkelmann-Duarte ◽  
Eduardo Cargnin-Ferreira ◽  
João B. Calixto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Matrix Metalloproteinase ◽  
Glial Cells ◽  
Transient Receptor Potential ◽  
Joint Damage ◽  
Receptor Potential ◽  
Pain Behavior ◽  
Transient Receptor Potential Vanilloid ◽  
Rat Spinal Cord ◽  
Transient Receptor

Transient receptor potential vanilloid 4 mediates protease activated receptor 2-induced sensitization of colonic afferent nerves and visceral hyperalgesia

2008 ◽  
Vol 294 (5) ◽  
pp. G1288-G1298 ◽  
Author(s):  
Walter E. B. Sipe ◽  
Stuart M. Brierley ◽  
Christopher M. Martin ◽  
Benjamin D. Phillis ◽  
Francisco Bautista Cruz ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Action Potentials ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Mechanical Hyperalgesia ◽  
Transient Receptor Potential Vanilloid ◽  
Afferent Neurons ◽  
Nociceptive Neurons ◽  
Afferent Fibers ◽  
Transient Receptor

Protease-activated receptor (PAR2) is expressed by nociceptive neurons and activated during inflammation by proteases from mast cells, the intestinal lumen, and the circulation. Agonists of PAR2 cause hyperexcitability of intestinal sensory neurons and hyperalgesia to distensive stimuli by unknown mechanisms. We evaluated the role of the transient receptor potential vanilloid 4 (TRPV4) in PAR2-induced mechanical hyperalgesia of the mouse colon. Colonic sensory neurons, identified by retrograde tracing, expressed immunoreactive TRPV4, PAR2, and calcitonin gene-related peptide and are thus implicated in nociception. To assess nociception, visceromotor responses (VMR) to colorectal distension (CRD) were measured by electromyography of abdominal muscles. In TRPV4+/+ mice, intraluminal PAR2 activating peptide (PAR2-AP) exacerbated VMR to graded CRD from 6–24 h, indicative of mechanical hyperalgesia. PAR2-induced hyperalgesia was not observed in TRPV4−/− mice. PAR2-AP evoked discharge of action potentials from colonic afferent neurons in TRPV4+/+ mice, but not from TRPV4−/− mice. The TRPV4 agonists 5′,6′-epoxyeicosatrienoic acid and 4α-phorbol 12,13-didecanoate stimulated discharge of action potentials in colonic afferent fibers and enhanced current responses recorded from retrogradely labeled colonic dorsal root ganglia neurons, confirming expression of functional TRPV4. PAR2-AP enhanced these responses, indicating sensitization of TRPV4. Thus TRPV4 is expressed by primary spinal afferent neurons innervating the colon. Activation of PAR2 increases currents in these neurons, evokes discharge of action potentials from colonic afferent fibers, and induces mechanical hyperalgesia. These responses require the presence of functional TRPV4. Therefore, TRPV4 is required for PAR2-induced mechanical hyperalgesia and excitation of colonic afferent neurons.

scholarly journals Chemokine CCL2 prevents opioid-induced inhibition of nociceptive synaptic transmission in spinal cord dorsal horn

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Mario Heles ◽  
Petra Mrozkova ◽  
Dominika Sulcova ◽  
Pavel Adamek ◽  
Diana Spicarova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Dorsal Horn ◽  
Transient Receptor Potential ◽  
Pain Treatment ◽  
Spinal Cord Dorsal Horn ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Receptors ◽  
Spinal Cord Dorsal

Abstract Background Opioid analgesics remain widely used for pain treatment despite the related serious side effects. Some of those, such as opioid tolerance and opioid-induced hyperalgesia may be at least partially due to modulation of opioid receptors (OR) function at nociceptive synapses in the spinal cord dorsal horn. It was suggested that increased release of different chemokines under pathological conditions may play a role in this process. The goal of this study was to investigate the crosstalk between the µOR, transient receptor potential vanilloid 1 (TRPV1) receptor and C–C motif ligand 2 (CCL2) chemokine and the involvement of spinal microglia in the modulation of opioid analgesia. Methods Patch-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) and dorsal root evoked currents (eEPSC) in spinal cord slices superficial dorsal horn neurons were used to evaluate the effect of µOR agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), CCL2, TRPV1 antagonist SB366791 and minocycline. Paw withdrawal test to thermal stimuli was combined with intrathecal (i.t.) delivery of CCL2 and DAMGO to investigate the modulation in vivo. Results Application of DAMGO induced a rapid decrease of mEPSC frequency and eEPSC amplitude, followed by a delayed increase of the eESPC amplitude, which was prevented by SB366791. Chemokine CCL2 treatment significantly diminished all the DAMGO-induced changes. Minocycline treatment prevented the CCL2 effects on the DAMGO-induced eEPSC depression, while mEPSC changes were unaffected. In behavioral experiments, i.t. injection of CCL2 completely blocked DAMGO-induced thermal hypoalgesia and intraperitoneal pre-treatment with minocycline prevented the CCL2 effect. Conclusions Our results indicate that opioid-induced inhibition of the excitatory synaptic transmission could be severely attenuated by increased CCL2 levels most likely through a microglia activation-dependent mechanism. Delayed potentiation of neurotransmission after µOR activation is dependent on TRPV1 receptors activation. Targeting CCL2 and its receptors and TRPV1 receptors in combination with opioid therapy could significantly improve the analgesic properties of opioids, especially during pathological states.

scholarly journals The Absence of the Transient Receptor Potential Vanilloid 1 Directly Impacts on the Expression and Localization of the Endocannabinoid System in the Mouse Hippocampus

2021 ◽  
Vol 15 ◽  
Author(s):  
Jon Egaña-Huguet ◽  
Itziar Bonilla-Del Río ◽  
Sonia M. Gómez-Urquijo ◽  
Amaia Mimenza ◽  
Miquel Saumell-Esnaola ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Transient Receptor Potential ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Receptor Potential ◽  
Perforant Path ◽  
Transient Receptor Potential Vanilloid ◽  
Excitatory Synapses ◽  
Selective Ligand ◽  
Transient Receptor

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective ligand-gated cation channel involved in synaptic transmission, plasticity, and brain pathology. In the hippocampal dentate gyrus, TRPV1 localizes to dendritic spines and dendrites postsynaptic to excitatory synapses in the molecular layer (ML). At these same synapses, the cannabinoid CB1 receptor (CB1R) activated by exogenous and endogenous cannabinoids localizes to the presynaptic terminals. Hence, as both receptors are activated by endogenous anandamide, co-localize, and mediate long-term depression of the excitatory synaptic transmission at the medial perforant path (MPP) excitatory synapses though by different mechanisms, it is plausible that they might be exerting a reciprocal influence from their opposite synaptic sites. In this anatomical scenario, we tested whether the absence of TRPV1 affects the endocannabinoid system. The results obtained using biochemical techniques and immunoelectron microscopy in a mouse with the genetic deletion of TRPV1 show that the expression and localization of components of the endocannabinoid system, included CB1R, change upon the constitutive absence of TRPV1. Thus, the expression of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) drastically increased in TRPV1−/− whole homogenates. Furthermore, CB1R and MAGL decreased and the cannabinoid receptor interacting protein 1a (CRIP1a) increased in TRPV1−/− synaptosomes. Also, CB1R positive excitatory terminals increased, the number of excitatory terminals decreased, and CB1R particles dropped significantly in inhibitory terminals in the dentate ML of TRPV1−/− mice. In the outer 2/3 ML of the TRPV1−/− mutants, the proportion of CB1R particles decreased in dendrites, and increased in excitatory terminals and astrocytes. In the inner 1/3 ML, the proportion of labeling increased in excitatory terminals, neuronal mitochondria, and dendrites. Altogether, these observations indicate the existence of compensatory changes in the endocannabinoid system upon TRPV1 removal, and endorse the importance of the potential functional adaptations derived from the lack of TRPV1 in the mouse brain.

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