Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models

Teodoro, Fernanda Cassanho; Júnior, Marcos F. Tronco; Zampronio, Aleksander Roberto; Martini, Alessandra Cadete; Rae, Giles A.; Chichorro, Juliana Geremias

doi:10.1016/j.npep.2012.10.005

Cited by 55 publications

(33 citation statements)

References 53 publications

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“…Specifically, SP, SP [8][9][10][11] and SP [1][2][3][4][5][6][7] were the most abundant peptide fragments observed. As suggested in Figure 1, C-terminal processing of Tach 20-68 by PC1 or PC2 can lead to the formation of SP.…”

Section: High-resolution Mass Spectrometry Analysismentioning

confidence: 96%

“…Data was acquired at a resolving power of 140,000 (FWHM), resulting to a scanning rate of ≈ 700 msec/scan when using automatic gain control target of 3.0x10 6 and maximum ion injection time of 200 msec. Product ion spectra were acquired a resolving power of 17,500 (FWHM), using automatic gain control target of 1.0x10 6 and maximum ion injection time of 100 msec. The collision energy set to 25 and the isolation window was set to 1.5 Da.…”

Section: Peptide Fragments Identificationmentioning

confidence: 99%

“…Besides, the Tac1 gene also encodes other tachykinins, including neuropeptide K (NPK) and neuropeptide γ (NPγ) [3]. SP is reported to play a critical role in nociceptive transmission in the CNS [4,5] and it is an agonist of the Neurokinin-1 receptor located in the lamina I of the spinal cord [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions

et al. 2015

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Section: High-resolution Mass Spectrometry Analysismentioning

confidence: 96%

Section: Peptide Fragments Identificationmentioning

confidence: 99%

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Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions

et al. 2015

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“…[50] Substance P, the primary ligand of Tachykinin receptor 1, is known to play a role in pain sensation and is linked to spinal cord injury and cutaneous neurogenic inflammation. [59] The upregulation of its receptor in HBSS mice may represent an increase in SP activity.…”

Section: Potential Mechanisms Of Scd-associated Painmentioning

confidence: 99%

Updated Mechanisms of Sickle Cell Disease-Associated Chronic pain

Lutz

Meiler

Bekker

et al. 2015

Transl Perioper & Pain Med

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Sickle cell disease (SCD), a hemoglobinopathy, can cause sickling of red blood cells, resulting in vessel blockage, stroke, anemia, inflammation, and extreme pain. A vast majority of SCD patients experience pain on a chronic basis, and many turn to opioids to provide limited relief. The side effects that come with chronic opioid use push for research into understanding the specific mechanisms of SCD-associated chronic pain. Current advances in SCD-associated pain have focused on alterations in the pain pathway including nociceptor sensitization and endogenous pain inducers. This article reviews the underlying pathophysiology of SCD, potential pain mechanisms, current treatments and their mechanism of action, and future directions of SCDassociated pain management. The information provided could help propel research in SCD-associated chronic pain and uncover novel treatment options for

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“…Substance P is a pronociceptive peptide and agonist of NK1 located in the lamina I of the spinal cord [Teodoro et al, 2013;Yu et al, 1999]. Substance P is primarily synthesized in neurons and has a widespread distribution in both the central and peripheral nervous systems.…”

Section: Introductionmentioning

confidence: 99%

Liquid chromatography-electrospray linear ion trap mass spectrometry analysis of targeted neuropeptides in Tac1−/− mouse spinal cords reveals significant lower concentration of opioid peptides

Saidi

Beaudry

2015

Neuropeptides

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Tachykinin and opioid peptides play a central role in pain transmission, modulation and inhibition. The treatment of pain is very important in medicine and many studies using NK1 receptor antagonists failed to show significant analgesic effects in humans. Recent investigations suggest that both pronociceptive tachykinins and the analgesic opioid systems are important for normal pain sensation. The analysis of opioid peptides in Tac1 -/-spinal cord tissues offers a great opportunity to verify the influence of the tachykinin system on specific opioid peptides. The objectives of this study were to develop a HPLC-MS/MRM assay to quantify targeted peptides in spinal cord tissues. Secondly, we wanted to verify if the Tac1 -/-mouse endogenous opioid system is hampered and therefore affect significantly the pain modulatory pathways. Targeted neuropeptides were analyzed by high performance liquid chromatography linear ion trap mass spectrometry. Our results reveal that EM-2, Leu-Enk and Dyn A were down-regulated in Tac1 -/-spinal cord tissues. Interestingly, Dyn A was almost 3 fold down-regulated (p < 0.0001). No significant concentration differences were observed in mouse Tac1 -/-spinal cords for Met-Enk and CGRP. The analysis of Tac1 -/-mouse spinal cords revealed noteworthy decreases of EM-2, Leu-Enk and Dyn A concentrations which strongly suggest a significant impact on the endogenous pain-relieving mechanisms. These observations may have insightful impact on future analgesic drug developments and therapeutic strategies.3

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Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models

Cited by 55 publications

References 53 publications

Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions

Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions

Updated Mechanisms of Sickle Cell Disease-Associated Chronic pain

Liquid chromatography-electrospray linear ion trap mass spectrometry analysis of targeted neuropeptides in Tac1−/− mouse spinal cords reveals significant lower concentration of opioid peptides

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