Noxious Cutaneous Thermal Stimuli Induce a Graded Release of Endogenous Substance P in the Spinal Cord: Imaging Peptide Action<i>In Vivo</i>

Allen, Brian; Rogers, Scott D.; Ghilardi, Joseph R.; Menning, Patrick M.; Kuskowski, Michael A.; Basbaum, Allan I.; Simone, Donald A.; Mantyh, Patrick W.

doi:10.1523/jneurosci.17-15-05921.1997

Cited by 142 publications

(97 citation statements)

References 46 publications

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“…The same stimulus (Abbadie et al, 1997), or one of shorter duration (30 sec) (Allen et al, 1997), have been used to evoke NK1R internalization. However, a thermal stimulus of longer duration was used to evoke Met-enkephalin release from the spinal cord (Cesselin et al, 1989): repeated (10 sec on and off) immersion of the rat's muzzle or tail in water at 52°C for 30 min.…”

Section: Resultsmentioning

confidence: 99%

“…This approach provides an ideal way to locate the areas of opioid release, because MORs serve as opioid detectors located in close proximity to opioid-releasing terminals and able to detect all naturally-occurring MOR agonists (Song and Marvizon, 2003a). Previously, neurokinin 1 receptor (NK1R) internalization had been used to measure substance P release (Abbadie et al, 1997;Allen et al, 1997;Honore et al, 1999;Kondo et al, 2005;Mantyh et al, 1995;Marvizon et al, 1997;Marvizon et al, 2003). Importantly, the magnitude of NK1R internalization increased with the intensity of the stimulus used to evoke substance P release, both when a noxious stimulus was used in vivo (Allen et al, 1997), or a chemical stimulus in vitro .…”

Section: Introductionmentioning

confidence: 99%

“…Previously, neurokinin 1 receptor (NK1R) internalization had been used to measure substance P release (Abbadie et al, 1997;Allen et al, 1997;Honore et al, 1999;Kondo et al, 2005;Mantyh et al, 1995;Marvizon et al, 1997;Marvizon et al, 2003). Importantly, the magnitude of NK1R internalization increased with the intensity of the stimulus used to evoke substance P release, both when a noxious stimulus was used in vivo (Allen et al, 1997), or a chemical stimulus in vitro . Likewise, MOR internalization increased with the intensity of the stimulus delivered to spinal cord slices to evoke opioid release (Song and Marvizon, 2003b).…”

Section: Introductionmentioning

confidence: 99%

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Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

et al. 2008

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The internalization of μ-opioid receptors (MORs) provides an ideal way to locate areas of opioid peptide release. We used this method to study opioid release in the spinal cord evoked by noxious stimuli in anesthetized rats. Previous studies have shown that opioids released in the spinal cord produce MOR internalization only when they are protected from peptidase degradation. Accordingly, rats were implanted with chronic intrathecal catheters that were used to inject a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) onto the lumbar spinal cord. Five minutes later, a noxious stimulus was delivered to the paw. Lumbar spinal segments were double-stained with antibodies against MORs and neurokinin 1 receptors (NK1Rs) using immunofluorescence. Mechanical stimulation of the hindpaw consisted of repeated 10 sec clamps with a hemostat for 10 min. In the ipsilateral dorsal horn, the stimulus produced abundant NK1R internalization in segments L3-L6, and a more modest but significant MOR internalization in segments L5 and L6. In the contralateral dorsal horn, NK1R was substantially lower and MOR internalization was negligible. The same mechanical stimulus applied to a forepaw did not produce NK1R or MOR internalization in the lumbar spinal cord. Thermal stimulation consisted of immersing a hindpaw in water at 52 °C for 2 min. It produced substantial NK1R internalization ipsilaterally in segment L6, but no MOR internalization. These results show that mechanical stimulation induces segmental opioid release, i.e., in the dorsal horn receiving the noxious signals and not in other spinal segments.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

et al. 2008

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“…In contrast, we show here that inhibitors of NEN and DEC produced a relatively smaller increase (2.8 -3.5 times) in the potencies of SP and NKA to produce NK1R internalization. Moreover, whereas peptidase inhibitors are required to observe m-opioid receptor internalization in dorsal horn neurons produced by endogenously released opioids (Song & Marvizon, 2003), endogenously released neurokinins produce abundant NK1R internalization in the absence of peptidase inhibitors (Mantyh et al, 1995;Allen et al, 1997;Liu et al, 1997;Marvizon et al, 1997;1999a;Cao et al, 1998;Honore et al, 1999;Riley et al, 2001). Therefore, it is possible to use peptidase inhibitors to enhance the analgesic effect of endogenous opioids (Noble et al, 1992b;Roques, 2000) without increasing NK1R activation by endogenous neurokinins.…”

Section: Jcg Marvizón Et Al Effect Of Peptidases On Nk1r Internalimentioning

confidence: 99%

“…NK1R activation was measured by their internalization, a technique validated in numerous studies (Mantyh et al, 1995;Allen et al, 1997;Liu et al, 1997;Marvizon et al, 1997;1999a;Cao et al, 1998;Honore et al, 1999;Riley et al, 2001). An additional goal of this study was to compare the potencies of SP, NKA and NKB to produce NK1R internalization.…”

Section: Introductionmentioning

confidence: 99%

Effect of peptidases on the ability of exogenous and endogenous neurokinins to produce neurokinin 1 receptor internalization in the rat spinal cord

Marvizón¹,

Wang

Lao³

et al. 2003

British J Pharmacology

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1 The ability of peptidases to restrict neurokinin 1 receptor (NK1R) activation by exogenously applied or endogenously released neurokinins was investigated by measuring NK1R internalization in rat spinal cord slices. 2 Concentration -response curves for substance P and neurokinin A were obtained in the presence and absence of 10 mM thiorphan, an inhibitor of neutral endopeptidase (EC 3.4.24.11), plus 10 mM captopril, an inhibitor of dipeptidyl carboxypeptidase (EC 3.4.15.1). These inhibitors significantly decreased the EC 50 of substance P to produce NK1R internalization from 32 to 9 nM, and the EC 50 of neurokinin A from 170 to 60 nM. 3 Substance P was significantly more potent than neurokinin A, both with and without these peptidase inhibitors. 4 In the presence of peptidase inhibitors, neurokinin B was 10 times less potent than neurokinin A and 64 times less potent than substance P (EC 50 ¼ 573 nM). 5 Several aminopeptidase inhibitors (actinonin, amastatin, bacitracin, bestatin and puromycin) failed to further increase the effect of thiorphan plus captopril on the NK1R internalization produced by 10 nM substance P. 6 Electrical stimulation of the dorsal root produced NK1R internalization by releasing endogenous neurokinins. Thiorphan plus captopril increased NK1R internalization produced by 1 Hz stimulation, but not by 30 Hz stimulation. 7 Therefore, NEN and DCP restrict NK1R activation by endogenous neurokinins when they are gradually released by low-frequency firing of primary afferents, but become saturated or inhibited when primary afferents fire at a high frequency.

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Neurokinin-1 receptor localisation in guinea pig autonomic ganglia

1999

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We have used multiple‐labelling immunohistochemistry and confocal microscopy to determine the distribution of immunoreactivity to the tachykinin neurokinin‐1 (NK1) receptors in guinea pig sympathetic ganglia. Although nerve fibres containing immunoreactivity to substance P were common in all ganglia except the superior cervical ganglia, most neurons expressing NK1 receptor immunoreactivity were not closely surrounded by pericellular baskets of substance P‐immunoreactive boutons. Conversely, many neurons surrounded by baskets of substance P‐immunoreactive boutons lacked NK1 immunoreactivity. In the coeliac and inferior mesenteric ganglia, NK1 receptor expression was restricted almost entirely to noradrenergic neurons that contained somatostatin immunoreactivity and projected to the enteric plexuses. In the lumbar chain and paracervical ganglia, NK1 immunoreactivity was expressed by nonnoradrenergic vasodilator neurons containing immunoreactivity to vasoactive intestinal peptide. Taken together, our results show that sympathetic neurons in different functional pathways express NK1 receptor immunoreactivity. However, the neurons that could respond to endogenously released substance P through NK1 receptors may be distant from presynaptic release sites. These observations suggest that, in sympathetic ganglia, substance P may modulate ganglionic transmission through heterosynaptic actions on NK1 receptors. J. Comp. Neurol. 412:693–704, 1999. © 1999 Wiley‐Liss, Inc.

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Noxious Cutaneous Thermal Stimuli Induce a Graded Release of Endogenous Substance P in the Spinal Cord: Imaging Peptide ActionIn Vivo

Cited by 142 publications

References 46 publications

Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

Effect of peptidases on the ability of exogenous and endogenous neurokinins to produce neurokinin 1 receptor internalization in the rat spinal cord

Neurokinin-1 receptor localisation in guinea pig autonomic ganglia

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