scholarly journals TRPV1 Receptors Contribute to Paclitaxel-Induced c-Fos Expression in Spinal Cord Dorsal Horn Neurons

2017 ◽  
pp. 549-552 ◽  
Author(s):  
N. KALYNOVSKA ◽  
P. ADAMEK ◽  
J. PALECEK
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Transient Receptor Potential ◽  
Spinal Cord Dorsal Horn ◽  
Transient Receptor Potential Vanilloid ◽  
Receptor Antagonists ◽  
Trpv1 Receptor ◽  
Dorsal Horn Neurons ◽  
Trpv1 Receptors

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.

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.

The Role of The TRPV1 Endogenous Agonist N-Oleoyldopamine in Modulation of Nociceptive Signaling at the Spinal Cord Level

2009 ◽  
Vol 102 (1) ◽  
pp. 234-243 ◽  
Author(s):  
Diana Spicarova ◽  
Jiri Palecek
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Spinal Cord Dorsal Horn ◽  
Transient Receptor Potential Vanilloid ◽  
High Concentration ◽  
Low Concentration ◽  
Trpv1 Receptors ◽  
Mepsc Frequency

Transient receptor potential vanilloid (TRPV1) receptors are abundant in a subpopulation of primary sensory neurons that convey nociceptive information from the periphery to the spinal cord dorsal horn. The TRPV1 receptors are expressed on both the peripheral and central branches of these dorsal root ganglion (DRG) neurons and can be activated by capsaicin, heat, low pH, and also by recently described endogenous lipids. Using patch-clamp recordings from superficial dorsal horn (DH) neurons in acute spinal cord slices, the effect of application of the endogenous TRPV1 agonist N-oleoyldopamine (OLDA) on the frequency of miniature excitatory postsynaptic currents (mEPSCs) was evaluated. A high concentration OLDA (10 μM) solution was needed to increase the mEPSC frequency, whereas low concentration OLDA (0.2 μM) did not evoke any change under control conditions. The increase was blocked by the TRPV1 antagonists SB366791 or BCTC. Application of a low concentration of OLDA evoked an increase in mEPSC frequency after activation of protein kinase C by phorbol ester (PMA) and bradykinin or in slices from animals with peripheral inflammation. Increasing the bath temperature from 24 to 34°C enhanced the basal mEPSC frequency, but the magnitude of changes in the mEPSC frequency induced by OLDA administration was similar at both temperatures. Our results suggest that presumed endogenous agonists of TRPV1 receptors, like OLDA, could have a considerable impact on synaptic transmission in the spinal cord, especially when TRPV1 receptors are sensitized. Spinal TRPV1 receptors could play a pivotal role in modulation of nociceptive signaling in inflammatory pain.

scholarly journals The role of spinal cord vanilloid (TRPV1) receptors in pain modulation

2008 ◽  
pp. S69-S77
Author(s):  
D Špicarová ◽  
J Paleček
Keyword(s):  
Spinal Cord ◽  
Transient Receptor Potential ◽  
Pain Modulation ◽  
Dorsal Root Ganglion Neurons ◽  
Spinal Cord Dorsal Horn ◽  
Transient Receptor Potential Vanilloid ◽  
Peripheral Tissues ◽  
Trpv1 Receptors ◽  
Ganglion Neurons

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.

scholarly journals Update on the Role of Spinal Cord TRPV1 Receptors in Pain Modulation

2014 ◽  
pp. S225-S236 ◽  
Author(s):  
D. SPICAROVA ◽  
V. NERANDZIC ◽  
J. PALECEK
Keyword(s):  
Spinal Cord ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Short Review ◽  
Pain Modulation ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Receptors ◽  
Transient Receptor ◽  
And Function

The structure, expression and function of the transient receptor potential vanilloid 1 (TRPV1) receptor were intensively studied since the cloning in 1997 and TRPV1 receptors are now considered to act as transducers and molecular integrators of nociceptive stimuli in the periphery. In contrast, spinal TRPV1 receptors were studied less extensively and their role in pain modulation is still not fully understood. This short review is a follow up on our previous summary in this area (Spicarova and Palecek 2008). The aim was to review preferentially the most recent findings concerning the role of the spinal TRPV1 receptors, published within the last five years. The update is given on the expression and function of the spinal TRPV1 receptors, their activation by endogenous agonists, interaction between the endocannabinoid and endovanillod system and possible role of the spinal TRPV1 receptors in pathological pain states. There is now mounting evidence that TRPV1 receptors may be an important element in modulation of nociceptive information at the spinal cord level and represent an interesting target for analgesic therapy.

Intra-arterial instillation of a nociceptive agent modulate cardiorespiratory parameters involving 5-HT3 and TRPV1 receptors in anesthetized rats

2021 ◽  
Vol 21 ◽  
Author(s):  
Sanjeev K. Singh ◽  
M. S. Muthu ◽  
Ravindran Revand ◽  
M. B. Mandal
Keyword(s):  
Transient Receptor Potential ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Neural Mechanisms ◽  
Transient Receptor Potential Vanilloid ◽  
Anesthetized Rats ◽  
Trpv1 Receptors ◽  
Perivascular Nerves ◽  
Transient Receptor

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 µM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin-induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 µg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.

scholarly journals Analgesic Effect of Acetaminophen: A Review of Known and Novel Mechanisms of Action

2020 ◽  
Vol 11 ◽  
Author(s):  
Nobuko Ohashi ◽  
Tatsuro Kohno
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Nociceptive Transmission ◽  
Spinal Dorsal ◽  
C Fibers ◽  
Trpv1 Receptors ◽  
The Brain

Acetaminophen is one of the most commonly used analgesic agents for treating acute and chronic pain. However, its metabolism is complex, and its analgesic mechanisms have not been completely understood. Previously, it was believed that acetaminophen induces analgesia by inhibiting cyclooxygenase enzymes; however, it has been considered recently that the main analgesic mechanism of acetaminophen is its metabolization to N-acylphenolamine (AM404), which then acts on the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid 1 receptors in the brain. We also recently revealed that the acetaminophen metabolite AM404 directly induces analgesia via TRPV1 receptors on terminals of C-fibers in the spinal dorsal horn. It is known that, similar to the brain, the spinal dorsal horn is critical to pain pathways and modulates nociceptive transmission. Therefore, acetaminophen induces analgesia by acting not only on the brain but also the spinal cord. In addition, acetaminophen is not considered to possess any anti-inflammatory activity because of its weak inhibition of cyclooxygenase (COX). However, we also revealed that AM404 induces analgesia via TRPV1 receptors on the spinal dorsal horn in an inflammatory pain rat model, and these analgesic effects were stronger in the model than in naïve rats. The purpose of this review was to summarize the previous and new issues related to the analgesic mechanisms of acetaminophen. We believe that it will allow clinicians to consider new pain management techniques involving acetaminophen.

Microglial refinement of spinal cord sensory circuitry regulates normal maturation of dynamic touch.

2021 ◽  
Author(s):  
Yajing Xu ◽  
Stephanie Koch ◽  
Alexander Chamessian ◽  
Qianru He ◽  
Mayya Sundukova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Normal Development ◽  
Physiological Role ◽  
Spinal Cord Dorsal Horn ◽  
Dynamic Touch ◽  
Tactile Sensitivity ◽  
Primary Afferent ◽  
Spinal Cord Dorsal

In the spinal cord dorsal horn, sensory circuits undergo remarkable postnatal reorganisation, including refinement of primary afferent A-fibres in the superficial layers, accompanied by decreased cutaneous sensitivity. Here we show a physiological role of microglia necessary for normal development of dorsal horn sensory circuits and tactile sensitivity. In the absence of microglial engulfment, superfluous A-fibre projections persist, leading to lifelong hypersensitivity to dynamic touch.

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