Substance P release in the dorsal horn assessed by receptor internalization: NMDA receptors counteract a tonic inhibition by GABABreceptors

1999 ◽  
Vol 11 (2) ◽  
pp. 417-426 ◽  
Author(s):  
Juan Carlos G. Marvizón ◽  
Eileen F. Grady ◽  
Enrico Stefani ◽  
Nigel W. Bunnett ◽  
Emeran A. Mayer
Keyword(s):  
Substance P ◽  
Nmda Receptors ◽  
Dorsal Horn ◽  
Tonic Inhibition ◽  
Receptor Internalization ◽  
P Release ◽  
Substance P Release

scholarly journals Effects of General Anesthetics on Substance P Release and c-Fos Expression in the Spinal Dorsal Horn

2013 ◽  
Vol 119 (2) ◽  
pp. 433-442 ◽  
Author(s):  
Toshifumi Takasusuki ◽  
Shigeki Yamaguchi ◽  
Shinsuke Hamaguchi ◽  
Tony L. Yaksh
Keyword(s):  
Nitrous Oxide ◽  
Substance P ◽  
Dorsal Horn ◽  
Receptor Internalization ◽  
General Anesthetics ◽  
Neurokinin 1 Receptor ◽  
P Release ◽  
Fos Expression ◽  
Neurokinin 1 ◽  
Substance P Release

Abstract Background: The authors examined in vivo the effects of general anesthetics on evoked substance P release (primary afferent excitability) and c-Fos expression (neuronal activation) in superficial dorsal horn. Methods: Rats received saline, propofol (100 mg/kg), pentobarbital (50 mg/kg), isoflurane (2 minimum alveolar concentration), nitrous oxide (66%), or fentanyl (30 μg/kg). During anesthesia, rats received intraplantar 5% formalin (50 μl) to left hind paw. Ten minutes later, rats underwent transcardial perfusion with 4% paraformaldehyde. Substance P release from small primary afferents was assessed by incidence of neurokinin 1 receptor internalization in the superficial dorsal horn. In separate studies, rats were sacrificed after 2 h and c-Fos expression measured. Results: Intraplantar formalin-induced robust neurokinin 1 receptor internalization in ipsilateral dorsal horn (ipsilateral: 54 ± 6% [mean ± SEM], contralateral: 12 ± 2%; P < 0.05; n = 4). Fentanyl, but not propofol, pentobarbital, isoflurane, nor nitrous oxide alone inhibited neurokinin 1 receptor internalization. However, 2 minimum alveolar concentration isoflurane + nitrous oxide reduced neurokinin 1 receptor internalization (27 ± 3%; P < 0.05; n = 5). All agents reduced c-Fos expression (control: 34 ± 4, fentanyl: 8 ± 2, isoflurane: 12 ± 3, nitrous oxide: 11 ± 2, isoflurane + nitrous oxide: 12 ± 1, pentobarbital: 11 ± 2, propofol: 13 ± 3; P < 0.05; n = 3). Conclusion: General anesthetics at anesthetic concentrations block spinal neuron activation through a mechanism that is independent of an effect on small primary afferent peptide release. The effect of fentanyl alone and the synergistic effect of isoflurane and nitrous oxide on substance P release suggest a correlative rationale for the therapeutic use of these anesthetic protocols by blocking nociceptive afferent transmitter release and preventing the initiation of cascade, which is immediately postsynaptic to the primary afferent.

Spinal substance P release in vivo during the induction of long-term potentiation in dorsal horn neurons

Pain ◽  
2002 ◽  
Vol 96 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Abdullahi Warsame Afrah ◽  
Atle Fiskå ◽  
Johannes Gjerstad ◽  
Henrik Gustafsson ◽  
Arne Tjølsen ◽  
...  
Keyword(s):  
Substance P ◽  
Dorsal Horn ◽  
Long Term Potentiation ◽  
Dorsal Horn Neurons ◽  
P Release ◽  
Term Potentiation ◽  
Substance P Release

Intradermal injection of capsaicin induces acute substance P release from rat spinal cord dorsal horn

2006 ◽  
Vol 410 (3) ◽  
pp. 183-186 ◽  
Author(s):  
Jing-Yin Yan ◽  
Rui-Qing Sun ◽  
Michael G. Hughes ◽  
David J. McAdoo ◽  
William D. Willis
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Dorsal Horn ◽  
Intradermal Injection ◽  
Spinal Cord Dorsal Horn ◽  
Rat Spinal Cord ◽  
P Release ◽  
Spinal Cord Dorsal ◽  
Substance P Release

scholarly journals Regulation by opioidergic interneurons of substance P release in rat spinal dorsal horn slices

1987 ◽  
Vol 43 ◽  
pp. 191
Author(s):  
Shigeki Kawabata ◽  
Ryoya Oku ◽  
Kazuhiro Okochi ◽  
Masamichi Satoh ◽  
Hiroshi Takagi
Keyword(s):  
Substance P ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Spinal Dorsal ◽  
P Release ◽  
Substance P Release

scholarly journals Regulation of Spinal Substance P Release by Intrathecal Calcium Channel Blockade

2011 ◽  
Vol 115 (1) ◽  
pp. 153-164 ◽  
Author(s):  
Toshifumi Takasusuki ◽  
Tony L. Yaksh
Keyword(s):  
Substance P ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Intrathecal Morphine ◽  
Receptor Internalization ◽  
Channel Blockers ◽  
Neurokinin 1 Receptor ◽  
P Release ◽  
Neurokinin 1 ◽  
Substance P Release

Background The authors investigated the role of different voltage-sensitive calcium channels expressed at presynaptic afferent terminals in substance P release and on nociceptive behavior evoked by intraplantar formalin by examining the effects of intrathecally delivered N- (ziconotide), T- (mibefradil), and L-type voltage-sensitive calcium channel blockers (diltiazem and verapamil). Methods Rats received intrathecal pretreatment with saline or doses of morphine, ziconotide, mibefradil, diltiazem, or verapamil. The effect of these injections upon flinching evoked by intraplantar formalin (5%, 50 μl) was quantified. To assess substance P release, the incidence of neurokinin-1 receptor internalization in the ipsilateral and contralateral lamina I was determined in immunofluorescent-stained tissues. Results Intrathecal morphine (20 μg), ziconotide (0.3, 0.6, and 1 μg), mibefradil (100 μg, but not 50 μg), diltiazem (500 μg, but not 300 μg), and verapamil (200 μg, but not 50 and 100 μg) reduced paw flinching in phase 2 compared with vehicle control (P < 0.05), with no effect on phase 1. Ziconotide (0.3, 0.6, and 1 μg) and morphine (20 μg) significantly inhibited neurokinin-1 receptor internalization (P < 0.05), but mibefradil, diltiazem, and verapamil at the highest doses had no effect. Conclusion These results emphasize the role in vivo of N-type but not T- and L-type voltage-sensitive calcium channel blockers in mediating the stimulus-evoked substance P release from small primary afferents and suggest that T- and L-type voltage-sensitive calcium channel blockers exert antihyperalgesic effects by an action on other populations of afferents or mechanisms involving postsynaptic excitability.

Modulation of reflex pressor response to contraction and effect on substance P release by spinal 5-HT1A receptors

1995 ◽  
Vol 268 (4) ◽  
pp. H1577-H1585 ◽  
Author(s):  
A. C. Nobrega ◽  
A. F. Meintjes ◽  
A. Ally ◽  
L. B. Wilson
Keyword(s):  
Substance P ◽  
Dorsal Horn ◽  
Pressor Response ◽  
Triceps Surae ◽  
P Release ◽  
Static Contraction ◽  
Passive Stretch ◽  
Static Contractions ◽  
Passive Muscle ◽  
Substance P Release

This study investigated whether activation of serotonin1A [5-hydroxytryptamine (5-HT)1A] receptors in the dorsal horn of the spinal cord attenuates the reflex pressor response to static contraction and passive muscle stretch. In addition, we determined if the attenuation of the response to contraction is mediated by inhibiting substance P (SP) release in the dorsal horn. Static contractions of the triceps surae muscle of chloralose-anesthetized cats were induced by stimulating the cut L7 and S1 ventral roots. Microdialysis (10 mM) of a selective 5-HT1A agonist [8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT)] into the L7 dorsal horn region produced a reversible attenuation of the reflex pressor response to a 1-min contraction (in mmHg: control = 36 +/- 3; 8-OH-DPAT = 17 +/- 3; recovery = 31 +/- 8; P = 0.013; n = 6) or passive stretch (in mmHg: control = 36 +/- 6; 8-OH-DPAT = 15 +/- 2; recovery = 32 +/- 6; P = 0.002; n = 6). However, a 5-HT1B agonist, 1-[3-(trifluoromethyl)-phenyl]piperazine, had no effect on the reflex pressor response. During 5-min contractions (n = 8), 8-OH-DPAT (10 mM) also blunted the pressor response but had no effect on the levels of SP-like immunoreactivity (in fmol/100 microliters: control = 0.492 +/- 0.026; 8-OH-DPAT = 0.501 +/- 0.034). These results suggest that activation of 5-HT1A receptors in the dorsal horn attenuates the reflex pressor response to contraction through a mechanism other than inhibition of SP release.

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