PGI2-induced activation and sensitization of articular mechanonociceptors

Birrell, G.J.; McQueen, Daniel S.; Iggo, A.; Coleman, Robert A.; Grubb, Blair D.

doi:10.1016/0304-3940(91)90809-8

Cited by 95 publications

(39 citation statements)

References 10 publications

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“…Previous studies indicated that PGI 2 , which can be secreted from MCs (Metcalfe et al, 1997), is capable of promoting activation and sensitization of articular mechanonociceptors (Birrell et al, 1991(Birrell et al, , 1993, but it is capable of only weakly activating visceral testicular nociceptors (Mizumura et al, 1991). Our results suggest that the PGI 2 sensitivity of meningeal nociceptors is similar to that of the knee joint with PGI 2 -mediated activation and sensitization of both A␦ units and C-units.…”

Section: Discussionsupporting

confidence: 59%

Sensitization and Activation of Intracranial Meningeal Nociceptors by Mast Cell Mediators

Zhang¹,

Strassman²,

Burstein³

et al. 2007

J Pharmacol Exp Ther

148

125

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Intracranial headaches such as migraine are thought to result from activation of sensory trigeminal pain neurons that supply intracranial blood vessels and the meninges, also known as meningeal nociceptors. Although the mechanism underlying the triggering of such activation is not completely understood, our previous work indicates that the local activation of the inflammatory dural mast cells can provoke a persistent sensitization of meningeal nociceptors. Given the potential importance of mast cells to the pain of migraine it is important to understand which mast cell-derived mediators interact with meningeal nociceptors to promote their activation and sensitization. In the present study, we have used in vivo electrophysiological single-unit recording of meningeal nociceptors in the trigeminal ganglion of anesthetized rats to examine the effect of a number of mast cell mediators on the activity level and mechanosensitivity of meningeal nociceptors. We have found that that serotonin (5-HT), prostaglandin I 2 (PGI 2 ), and to a lesser extent histamine can promote a robust sensitization and activation of meningeal nociceptors, whereas the inflammatory eicosanoids PGD 2 and leukotriene C 4 are largely ineffective. We propose that dural mast cells could promote headache by releasing 5-HT, PGI 2 , and histamine.

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Section: Discussionsupporting

confidence: 59%

Sensitization and Activation of Intracranial Meningeal Nociceptors by Mast Cell Mediators

Zhang¹,

Strassman²,

Burstein³

et al. 2007

J Pharmacol Exp Ther

148

125

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“…Prostaglandins (PGs) and leukotrienes cause sensitization of the peripheral receptors, reducing their activation threshold and increasing their responsiveness to other stimuli. [4][5][6] Kinins, such as bradykinin and kallidin have numerous pro-inflammatory functions including: release of PGs, cytokines and free radicals from a variety of cells; degranulation of mast cells and release of histamine; and stimulation of sympathetic neurons to alter blood vessel caliber. 7 Kinins also contribute to plasma extravasation by producing contraction of vascular endothelial cells.…”

Section: Transductionmentioning

confidence: 99%

Preemptive analgesia I: physiological pathways and pharmacological modalities

Kelly

Ahmad

Brull

2001

Can J Anesth/J Can Anesth

259

181

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P Pu ur rp po os se e: : This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia.S So ou ur rc ce e: : Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents.P Pr ri in nc ci ip pa al l f fi in nd di in ng gs s: : The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (Nmethyl-D-aspartate) -and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain.C Co on nc cl lu us si io on n: : The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.Objectif : La présente revue, en deux parties, résume les connaissances actuelles sur les mécanismes physiologiques et les modalités pharmacologiques de lanalgésie préventive ainsi que sur les questions controversées qui lentourent.Sources : Des articles, de 1966 à aujourdhui, obtenus à partir des bases de données MEDLINE. Les termes de la recherche compren-

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“…PGE 2 (Sigma) was used in this study because it is a well characterized direct-acting hyperalgesic inflammatory mediator. PGE 2 is released in peripheral tissue and the spinal cord after injury, and it sensitizes nociceptors while causing little direct activation [depolarization and generation of action potentials (Birrell et al, 1991)]. Furthermore, inhibition of prostaglandin biosynthesis appears to be the mechanism underlying the antinociceptive effects of the widely used aspirinlike nonsteroidal anti-inflammatory analgesics (Vane, 1971;Ferreira, 1972).…”

Section: Methodsmentioning

confidence: 99%

Modulation of TTX-RI_Naby PKC and PKA and Their Role in PGE₂-Induced Sensitization of Rat Sensory NeuronsIn Vitro

1998

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A tetrodotoxin-resistant voltage-gated Na ϩ current (TTX-R I Na ) appears to be the current primarily responsible for action potential generation in the cell body and terminals of nociceptive afferents. Although other voltage-gated Na ϩ currents are modulated by the activation of protein kinase C (PKC), protein kinase A (PKA), or both, the second messenger pathways involved in the modulation of TTX-R I Na are still being defined. We have examined the modulation of TTX-R I Na in isolated sensory neurons with whole-cell voltage-clamp recording. Activation of either PKC or PKA increased TTX-R I Na . PKA activation also produced a leftward shift in the conductancevoltage relationship of TTX-R I Na and an increase in the rates of current activation, deactivation, and inactivation. Inhibitors of PKC decreased TTX-R I Na , whereas inhibitors of PKA had no effect on the current. Investigating the interaction between PKC and PKA revealed that although inhibitors of PKA had little effect on PKC-induced modulation of TTX-R I Na , inhibitors of PKC significantly attenuated PKA-induced modulation of the current. Finally, although PGE 2 -induced modulation of TTX-R I Na was more similar to PKA-induced modulation of the current than to PKC-induced modulation, PGE 2 -induced effects were inhibited by inhibitors of both PKC and PKA. Thus, although TTX-R I Na is a common target for cellular processes involving the activation of either PKA or PKC, PKC activity is necessary to enable subsequent PKA-mediated modulation of TTX-R I Na . Key words: dorsal root ganglion; inflammatory mediator; nociception; pain; primary afferent; second-messengerStudies of voltage-gated sodium currents (VGSC s) indicate that VGSC isoforms may be differentially modulated by protein kinase C (PKC) and protein kinase A (PK A). For example, a VGSC from brain tissue is decreased by the concurrent activation of PKC and PK A (Gershon et al., 1992;Li et al., 1992; Cantrell et al., 1996 Cantrell et al., , 1997, and a VGSC from cardiac muscle is decreased by PKC activation (Qu et al., 1994) and increased by PK A activation (Frohnwieser et al., 1995(Frohnwieser et al., , 1997. That these changes in VGSCs are physiologically relevant is suggested by the observations that receptor-mediated changes in cellular excitability reflect, at least in part, PKC -and /or PK A-mediated changes in VGSCs.We and others have recently demonstrated that a tetrodotoxinresistant voltage-gated Na ϩ current (TTX-R I Na ), expressed primarily in nociceptive afferents, is modulated by hyperalgesic inflammatory mediators in a manner that is likely to enhance nociceptor excitability (England et al., 1996;Gold et al., 1996b; Cardenas et al., 1997). Although there is evidence both for (England et al., 1996) and against (C ardenas et al., 1997) a role for protein kinase A in the modulation of TTX-R I Na , the contribution of PKC has yet to be investigated.Using agents that activate or inhibit PKC and PK A, we have tested the hypothesis that these kinases are involved in the modulation of T...

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PGI2-induced activation and sensitization of articular mechanonociceptors

Cited by 95 publications

References 10 publications

Sensitization and Activation of Intracranial Meningeal Nociceptors by Mast Cell Mediators

Sensitization and Activation of Intracranial Meningeal Nociceptors by Mast Cell Mediators

Preemptive analgesia I: physiological pathways and pharmacological modalities

Modulation of TTX-RI_Naby PKC and PKA and Their Role in PGE₂-Induced Sensitization of Rat Sensory NeuronsIn Vitro

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PGI2-induced activation and sensitization of articular mechanonociceptors

Cited by 95 publications

References 10 publications

Sensitization and Activation of Intracranial Meningeal Nociceptors by Mast Cell Mediators

Sensitization and Activation of Intracranial Meningeal Nociceptors by Mast Cell Mediators

Preemptive analgesia I: physiological pathways and pharmacological modalities

Modulation of TTX-RINaby PKC and PKA and Their Role in PGE2-Induced Sensitization of Rat Sensory NeuronsIn Vitro

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Product

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Modulation of TTX-RI_Naby PKC and PKA and Their Role in PGE₂-Induced Sensitization of Rat Sensory NeuronsIn Vitro