TRPs and Pain

Sexton, Jane E.; Vernon, Jeffrey; Wood, John N.

doi:10.1007/978-3-319-05161-1_6

Cited by 22 publications

(16 citation statements)

References 144 publications

(179 reference statements)

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“…The present study corroborates the fact that modification of OA in C 3 and C 28 positions results in enhancement of biological properties. Furthermore, all oleanane-derived compounds also display superior analgesic activity in formalin-induced pain [ 23 ]. The formalin test is a useful nociceptive model in that pain is spontaneous and responses are observed in freely moving animals.…”

Section: Discussionmentioning

confidence: 99%

Semisynthesis of Derivatives of Oleanolic Acid fromSyzygium aromaticumand Their Antinociceptive and Anti-Inflammatory Properties

Rali

Oyedeji

Aremu

et al. 2016

Mediators of Inflammation

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Oleanolic acid is a pentacyclic triterpenoid compound widely found in plants and well known for its medicinal properties. Oleanolic acid (OA) was isolated from the ethyl acetate extract of Syzygium aromaticum flower buds. Semisynthesis afforded both acetate and ester derivatives. The derived compounds were monitored with thin layer chromatography and confirmed with nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), Fourier infrared (FT-IR) spectroscopy, and melting point (Mp). All these compounds were evaluated for their analgesic and anti-inflammatory properties at a dose of 40 mg/kg. Significant analgesic and anti-inflammatory effects were noted for all OA-derived compounds. In the formalin-induced pain test, the derivatives showed better analgesic effects compared to their precursor, whereas, in the tale flick test, oleanolic acid proved to be superior in analgesic effects compared to all its derivatives with the exception of the acetyl derivative. Acute inflammatory tests showed that acetyl derivatives possessed better anti-inflammatory activity compared to the other compounds. In conclusion, semisynthesis of oleanolic acid yielded several derivatives with improved solubility and enhanced analgesic and anti-inflammatory properties.

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Section: Discussionmentioning

confidence: 99%

Semisynthesis of Derivatives of Oleanolic Acid fromSyzygium aromaticumand Their Antinociceptive and Anti-Inflammatory Properties

Rali

Oyedeji

Aremu

et al. 2016

Mediators of Inflammation

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“…Depending on the inciting event (inflammation, nerve injury), not only peripheral but also spinal and/or supraspinal signaling pathways can all conspire to amplify and produce persistence of pain [4–6]. At the level of the nociceptor, the basis of acute inflammatory pain and its persistence has been studied with a focus on inflammation-induced modifications of ion channel function that result in lowering activation thresholds in the presence of the ongoing production of endogenous sensitizing molecules [3, 7, 8]. However, other processes that drive the persistence and transition from acute to chronic pain continue to be examined [5, 9–12].…”

Section: Introductionmentioning

confidence: 99%

Transcription factor Sp4 is required for hyperalgesic state persistence

et al. 2019

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Understanding how painful hypersensitive states develop and persist beyond the initial hours to days is critically important in the effort to devise strategies to prevent and/or reverse chronic painful states. Changes in nociceptor transcription can alter the abundance of nociceptive signaling elements, resulting in longer-term change in nociceptor phenotype. As a result, sensitized nociceptive signaling can be further amplified and nocifensive behaviors sustained for weeks to months. Building on our previous finding that transcription factor Sp4 positively regulates the expression of the pain transducing channel TRPV1 in Dorsal Root Ganglion (DRG) neurons, we sought to determine if Sp4 serves a broader role in the development and persistence of hypersensitive states in mice. We observed that more than 90% of Sp4 staining DRG neurons were small to medium sized, primarily unmyelinated (NF200 neg) and the majority co-expressed nociceptor markers TRPV1 and/or isolectin B4 (IB4). Genetically modified mice (Sp4+/-) with a 50% reduction of Sp4 showed a reduction in DRG TRPV1 mRNA and neuronal responses to the TRPV1 agonist—capsaicin. Importantly, Sp4+/- mice failed to develop persistent inflammatory thermal hyperalgesia, showing a reversal to control values after 6 hours. Despite a reversal of inflammatory thermal hyperalgesia, there was no difference in CFA-induced hindpaw swelling between CFA Sp4+/- and CFA wild type mice. Similarly, Sp4+/- mice failed to develop persistent mechanical hypersensitivity to hind-paw injection of NGF. Although Sp4+/- mice developed hypersensitivity to traumatic nerve injury, Sp4+/- mice failed to develop persistent cold or mechanical hypersensitivity to the platinum-based chemotherapeutic agent oxaliplatin, a non-traumatic model of neuropathic pain. Overall, Sp4+/- mice displayed a remarkable ability to reverse the development of multiple models of persistent inflammatory and neuropathic hypersensitivity. This suggests that Sp4 functions as a critical control point for a network of genes that conspire in the persistence of painful hypersensitive states.

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“…In studies conducted using human tissue, TRPV1 and TRPV3 levels were found to be decreased in the skin of patients with diabetic or other painful neuropathies but increased in intact nerve fibers in certain patients with pain hypersensitivity, whereas the level of TRPV4 was observed to remain unchanged [99,155]. One potential mechanism has been suggested for these phenotypic changes: the damaged neurons might release growth factors and neurotransmitters into the surrounding area and, consequently, cause an increase in the excitability of surrounding neurons [13, 153,156,157]. These dynamic changes contrast the changes detected in inflammation, in which TRP channels are generally upregulated (see above); this reflects the notion that inflammatory pain simply features a Bsurplus^of nociceptive signaling, whereas the sensory abnormalities of neuropathies include not only hypersensitivity (hyperalgesia or allodynia), but also paresthesias, hypoesthesia, or complete deficits perceived as numbness [158] (Fig.…”

Section: Trps In Neuropathic Painmentioning

confidence: 98%

TRPs and pain

2015

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Nociception is the process of transmission of painful signals by nociceptors in the primary afferent nerve fibers, which specifically respond to noxious stimuli. These noxious stimuli are detected by nociceptors and converted into electrical signals, which are then transmitted to the spinal cord, thalamus, and the cerebral cortex, where pain is finally sensed. Transient receptor potential (TRP) ion channels have emerged as a family of evolutionarily conserved ligand-gated ion channels that function as molecular detectors of physical stimuli. Several member of this family, at least six channels from three TRP family subtypes (TRPV1-4, TRPM8, and TRPA1), are expressed in nociceptors, where they act as transducers for signals from thermal, chemical, and mechanical stimuli and play crucial roles in the generation and development of pathological pain perception. This review focuses on the increasing evidence of TRP channel involvement and contribution in nociceptive pain and the pain hypersensitivity associated with peripheral inflammation or neuropathy, and on the renewed interest in targeting TRP channels for pain relief.

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TRPs and Pain

Cited by 22 publications

References 144 publications

Semisynthesis of Derivatives of Oleanolic Acid fromSyzygium aromaticumand Their Antinociceptive and Anti-Inflammatory Properties

Semisynthesis of Derivatives of Oleanolic Acid fromSyzygium aromaticumand Their Antinociceptive and Anti-Inflammatory Properties

Transcription factor Sp4 is required for hyperalgesic state persistence

TRPs and pain

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