Pharmacological properties of a C‐fibre response evoked by saphenous nerve stimulation in an isolated spinal cord‐nerve preparation of the newborn rat

Nussbaumer, J.C.; Yanagisawa, Mitsuhiko; Otsuka, Masanori

doi:10.1111/j.1476-5381.1989.tb12607.x

Cited by 79 publications

(43 citation statements)

References 44 publications

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“…Finally, it is possible that spantide activates an alternative receptor that mediates an overriding vasoconstriction or blocks the capsaicin receptor. The presence of more than one type of spantide-susceptible tachykinin receptor has been previously suggested (Chahl, 1985;Featherstone, Fosbraey & Morton, 1986;Buck & Shatzer, 1988;Nussbaumer, Yanagisawa & Otsuka, 1989).…”

Section: Discussionmentioning

confidence: 99%

Influence of perivascular peptides on endoneurial blood flow and microvascular resistance in the sciatic nerve of the rat.

Zochodne

1991

The Journal of Physiology

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SUMMARY1. A variety of vasoactive peptides has been identified in the axon terminals innervating vasa nervorum but their function is unknown. In mesenteric arterioles, substance P (SP) and calcitonin gene-related peptide (CGRP) have been postulated to have a role in tonic vasodilatation.2. We explored the effect of epineurial capsaicin, SP, CGRP, spantide (SP antagonist), and hCGRP (8-37) (CGRP antagonist) on blood flow (EBF) and microvascular resistance (EMR) in the endoneurial compartment of the rat sciatic nerve, as measured by hydrogen clearance.3. Epineurial capsaicin induced a prompt, intense and prolonged increase in EBF and lowering of EMR as compared to epineurial application of the carrier alone in a separate animal group. The hyperaemic response was also confirmed by studying serial clearance curves in individual animals.4. Multifibre sciatic-tibial motor conduction was not changed by epineurial capsaicin.5. When co-administered with capsaicin, hCGRP (8-37) completely blocked the hyperaemic response and increased EMR above the pooled control range. Spantide also blocked the capsaicin response.6. When administered alone, both epineurial hCGRP (8-37) and spantide lowered EBF below and increased EMR above the control measurements in the same animals.7. At 10-M epineurial CGRP, but not SP lowered EMR. Vasodilatation from intra-arterial administration of CGRP was much greater and was more prolonged compared with that induced by SP. hCGRP (8-37), but not spantide reduced the intra-arterial response to CGRP.8. The findings suggest that epineurial peptidergic terminals mediate a vasodilatory response (particularly through CGRP) that increases blood flow in the 'downstream' endoneurial compartment. Physiological peptide release (blocked by SP and CGRP receptor antagonism) may be important in maintaining tonic vasodilatation.

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Section: Discussionmentioning

confidence: 99%

Influence of perivascular peptides on endoneurial blood flow and microvascular resistance in the sciatic nerve of the rat.

Zochodne

1991

The Journal of Physiology

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“…Previous studies have shown that the slow VRPs induced by both saphenous nerve stimulation and application of capsaicin to skin were markedly depressed by a tachykinin antagonist spantide (Nussbaumer et al, 1989;Yanagisawa et al, 1992). There is evidence that these slow depolarizing responses represent a component of nociceptive spinal reflexes (Nussbaumer et al, 1989;Yanagisawa et al, 1992). (Yoshioka et al, 1990b), these concentrations would be sufficiently high to block other types of muscarinic receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Isolated spinal cord-saphenous nerve preparation The hemisected spinal cord below the middle thoracic level was isolated together with the attached L3-L5 ventral roots and dorsal roots, the latter remaining connected with the dorsal root ganglia and the femoral and saphenous nerves (Nussbaumer et al, 1989). The saphenous nerve was stimulated supramaximally with one to five pulses of 500 ys duration and 30-40 V intensity at 50 Hz and the potential changes were recorded from the L3 ventral root on a pen recorder.…”

Section: Preparationsmentioning

confidence: 99%

“…These responses are presumably mediated by different types of muscarinic receptors (Newberry & Connolly, 1989;Yoshioka et al, 1990b), but their pharmacological properties have not been fully characterized. In isolated spinal cord preparations, activation of primary afferent fibres by either electrical stimulation or peripheral noxious stimulation evokes a depolarization of slow time course in ventral roots (Yanagisawa et al, 1982;Akagi et al, 1985;Otsuka & Yanagisawa, 1988;Nussbaumer et al, 1989;Yanagisawa et al, 1992). There is evidence that this depolarization, hereafter referred to as the slow ventral root potential (VRP), represents a C-fibre-evoked nociceptive response in which tachykininergic primary afferents are involved (Otsuka & Yanagisawa, 1987).…”

Section: Introductionmentioning

confidence: 99%

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Muscarinic excitatory and inhibitory mechanisms involved in afferent fibre‐evoked depolarization of motoneurones in the neonatal rat spinal cord

Kurihara

Suzuki

Yanagisawa

et al. 1993

British J Pharmacology

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1 The involvement of acetylcholine and muscarinic receptors in spinal synaptic responses evoked by electrical and noxious sensory stimuli was investigated in the neonatal rat spinal cord in vitro. 2 Potentials were recorded extracellularly from a ventral root (L3-L5) of the isolated spinal cord, spinal cord-cutaneous nerve, and spinal cord-skin preparations of 1-to 4-day-old rats. Spinal reflexes were elicited by electrical stimulation of the ipsilateral dorsal root or the cutaneous saphenous nerve, or by noxious skin stimulation.3 Single shock stimulation of supramaximum intensity of a dorsal root induced a mono-synaptic reflex in the corresponding ventral root. Bath-application of the muscarinic agonists, muscarine (0.3-30 9M) and (+ )-cis-dioxolane (0.1-100 9AM), produced an inhibition of the mono-synaptic reflex and a depolarization of motoneurones. Other muscarinic agonists, arecoline (10 nM-10 AM) and oxotremorine (1OnM-1 tM), inhibited the mono-synaptic reflex with little or no depolarization of motoneurones.Repetitive stimulation of the saphenous nerve at C-fibre strength induced a slow depolarizing response lasting about 30 s of the L3 ventral root. This slow ventral root potential (VRP) was also inhibited by arecoline (10 nM-1I0 AM) and oxotremorine (10 nM-1 9AM). 4 In the spinal cord-saphenous nerve-skin preparation, a slow VRP was evoked by application of capsaicin (0.5 9AM), bradykinin (3 9AM), or noxious heat (47°C) to skin. This slow VRP was depressed by the muscarinic agonists, arecoline (3 9AM) and oxotremorine (1 9AM). 5 Of the (+)-cis-dioxolane-induced inhibition of mono-synaptic reflex and motoneurone depolarization, the M2 antagonists, AF-DX 116 (0.1-1I9M) and methoctramine (100-300 nM), preferentially blocked the former response, whereas the M3 antagonists, 4-DAMP (3-10 nM) and p-F-HHSiD (0.3-3 AM), preferentially blocked the latter response. AF-DX 116 (0.1-1I9M) and methoctramine (100-300 nM) also effectively antagonized the arecoline-and oxotremorine-induced inhibition of the slow VRP. The pA2 values of AF-DX 116 and methoctramine against the arecoline-induced inhibition of the mono-synaptic reflex were both 6.79, and that of 4-DAMP against the (+)-cis-dioxolane-induced motoneurone depolarization was 8.16. 6 In the spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow VRP was augmented by the anticholinesterase, edrophonium (5 9AM). (1 AM) and methoctramine (100 nM) also potentiated the slow VRP, whereas 4-DAMP (10 nM) depressed the response. 4-DAMP (5-10 nM) depressed the capsaicin-induced slow VRP in the spinal cord-skin preparation. 7 Oxotremorine (0.3 9lM) and arecoline (1 AM) markedly depressed the depolarization of motoneurones evoked by application of capsaicin (3 9AM) to the spinal cord, whereas they depressed only slightly the depolarization induced by substance P (10 nM). 8 The present study suggests that both excitatory (via M3-type receptors) and inhibitory (via M2-type receptors) muscarinic mechanisms are involved in afferent fibre-evoked nociceptive tr...

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“…This preparation enables us to obtain stable extracellular recording from ventral roots and thus to carry out detailed pharmacological analyses of both responses to nerve stimulation and responses to exogenously applied agents. Activation of primary afferent fibres by either electrical stimulation at C-fibre strength or peripheral noxious stimulation evokes a depolarization of a slow time course in ventral roots and this depolarization is markedly depressed by tachykinin antagonists as well as opioid agonists (Akagi et al, 1985;Otsuka & Yanagisawa, 1988;Nussbaumer et al, 1989;Yanagisawa et al, 1992;Guo et al, 1993;Hosoki et al, 1994). These and other lines of evidence suggest that this depolarization, hereafter referred to as the slow ventral root potential (VRP), represents a C-fibre-evoked nociceptive response in which tachykininergic primary afferents are involved (Otsuka & Yanagisawa, 1987).…”

Section: Introductionmentioning

confidence: 99%

The excitatory and inhibitory modulation of primary afferent fibre‐evoked responses of ventral roots in the neonatal rat spinal cord exerted by nitric oxide

Kurihara¹,

Yoshioka²

1996

British J Pharmacology

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1 We investigated the role of nitric oxide (NO) in modulating spinal synaptic responses evoked by electrical and noxious sensory stimuli in the neonatal rat spinal cord in vitro. 2 Potentials were recorded extracellularly from a ventral root (L3 -L5) of the isolated spinal cord preparation or spinal cord-saphenous nerve-skin preparation of 0-to 2-day-old rats. Spinal reflexes were elicited by electrical stimulation of the ipsilateral dorsal root or by noxious skin stimulation. 3 In the spinal cord preparation, single shock stimulation of a dorsal root at C-fibre strength induced mono-synaptic reflex followed by a slow depolarizing response lasting about 30 s (slow ventral root potential; slow VRP) in the ipsilateral ventral root of the same segment. Bath-application of NO gascontaining medium (l0-4-10-2 dilution of saturated medium) and NO donors, 1-hydroxy-2-oxo-3-(Nethyl-2-aminoethyl)-3-ethyl-1-triazene (NOC12, 3-300 gM), S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 3-300 gM) and S-nitroso-L-glutathione (GSNO, 3-300 gM), produced an inhibition of the slow VRP and a depolarization of ventral roots. Another NO donor, 3-morpholinosydononimine (SIN-1, 30-300 gM), also depressed the slow VRP but did not depolarize ventral roots. These agents did not affect the mono-synaptic reflex. 4 In the spinal cord-saphenous nerve-skin preparation, application of capsaicin (0.1-0.2 gM) to skin evoked a slow depolarizing response of the L3 ventral root. This slow VRP was depressed by NOC12 (10-300 gM) and SIN-I (100-300 gM). When the concentration of NOC12 was increased to 1 mM, spontaneous synaptic activities were augmented and the depressant effect of NOC12 on the slow VRP became less pronounced.5 A NO-scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl-3-oxide(carboxy-PTIO, 100-300 pM) prevented the depressant effect on the dorsal root-evoked slow VRP and ventral root depolarizing effects of NO donors. Carboxy-PTIO increased spontaneous synaptic activities and markedly potentiated the slow VRP. A NO synthase (NOS) inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME, 0.03-1 uM), but not D-NAME (0.03-1 gM), also markedly potentiated the slow VRP and this effect was reversed by L-arginine (300 gM). 6 8-Bromo-cyclic guanosine 3': 5'-monophosphate (8-Br-cyclic GMP, 100-300 gM) produced both an inhibition of the slow VRP and a depolarization of ventral roots. A cyclic GMP-dependent protein kinase inhibitor, KT5823 (0.3 gM), partly inhibited the depressant effects of NO donors and 8-Br-cyclic GMP on the dorsal root-evoked slow VRP. In contrast, KT5823 did not inhibit the depolarizing effects of NO donors.7 Perfusion of the spinal cord with medium containing tetrodotoxin (0.3 gM) and/or low Ca21 (0.1 mM)-high Mg2e (10 mM) markedly potentiated the depolarizing effect of NO donors. The SNAPevoked depolarization in the tetrodotoxin-containing low Ca2+-high Mg2+ medium was significantly inhibited by excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (30 MM) and 6-cyano-7-nitroquinoxaline-...

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Pharmacological properties of a C‐fibre response evoked by saphenous nerve stimulation in an isolated spinal cord‐nerve preparation of the newborn rat

Cited by 79 publications

References 44 publications

Influence of perivascular peptides on endoneurial blood flow and microvascular resistance in the sciatic nerve of the rat.

Influence of perivascular peptides on endoneurial blood flow and microvascular resistance in the sciatic nerve of the rat.

Muscarinic excitatory and inhibitory mechanisms involved in afferent fibre‐evoked depolarization of motoneurones in the neonatal rat spinal cord

The excitatory and inhibitory modulation of primary afferent fibre‐evoked responses of ventral roots in the neonatal rat spinal cord exerted by nitric oxide

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