Cutaneous inputs to dorsal horn neurones in adult rats treated at birth with capsaicin

Cervero, F.; Shouenborg, J.; Sjölund, Bengt H.; Waddell, P.J.

doi:10.1016/0006-8993(84)90401-3

Cited by 62 publications

(10 citation statements)

References 25 publications

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“…The same types of conditioning stimuli have been directly shown to produce increases in excitability in dorsal horn neurones. Thus, high intensity electrical stimuli with stimulus parameters very similar to those used in the present study have been shown to evoke transient increases in the excitability of rat dorsal horn neurones (Cervero et al, 1984;Cook et al, 1989). Several types of 'natural' noxious stimulation of the periphery have been shown to produce increased excitability in dorsal horn neurones (Hoheisel & Mense, 1989;Hylden et al, 1989;Laird & Cervero, 1989;Neugebauer & Schaible, 1990;Woolf & King, 1990) and also in thalamic neurones (Guildbaud et al, 1987).…”

Section: Pharmacokineticssupporting

confidence: 52%

Effect of RP 67580, a non‐peptide neurokinin₁ receptor antagonist, on facilitation of a nociceptive spinal flexion reflex in the rat

Laird¹,

Hargreaves²,

Hill³

1993

British J Pharmacology

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1 In order to examine the contribution of neurokinin, (NKI) receptors to facilitation of a spinal nociceptive reflex in the rat, we have investigated the effects of RP 67580 ((3aR,7aR)-7,7-diphenyl-2(1-imino-2-(2-methoxyphenyl/ethyl)perhydroisoindole)), a non-peptide neurokinin, (NK,) receptor antagonist, selective for the rodent receptor sub-type, on the activity of individual motorunits. These results were compared with the effects of RP 68651, the inactive 3aS, 7aS enantiomer of RP 67580, as a control for non-specific activity. 2 Experiments were performed on 15 rats anaesthetized with a continuous i.v. infusion of alphaxalone/ alphadalone and spinalized at T9-10. Single unit recordings of motorunit activity from biceps femoris/ semitendinosus were made with a concentric needle electrode. In each experiment, a vehicle dose followed by 4 sequential rising doses of either RP 67580 or RP 68651 were given at 15 min intervals. High intensity electrical stimuli were applied to the hindlimb receptive field of the motorunit at a rate of 1 per 60 s throughout the experiment to establish a baseline. A conditioning stimulus (20 of these stimuli at 1 Hz) was delivered 5 min after each dose and the effect of the size of the baseline response examined. 3 The conditioning stimulus evoked a facilitation of the baseline at the start of all experiments (mean increase ± s.e.mean = 151 ± 20%). RP 67580 attenuated this facilitation, with an IDso (± s.e.mean) of 2.5 ± 4.2 fg kg-', i.v., whereas RP 68651 at doses of up to 3 mg kg', i.v. did not. There was no statistically significant effect of drug on the baseline reflex, nor on the response to the conditioning stimulus. Doses of 300 and 3000 Itg kg-' of both RP 67580 and RP 68651 evoked small depressor effects on systemic arterial blood pressure. 4 We conclude that the facilitation of a spinal flexor reflex by noxious conditioning stimuli in the rat is mediated by NK, receptors whereas the baseline reflex is not. The results suggest that brain penetrant NK, receptor antagonists may have central anti-nociceptive effects.

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Section: Pharmacokineticssupporting

confidence: 52%

Effect of RP 67580, a non‐peptide neurokinin₁ receptor antagonist, on facilitation of a nociceptive spinal flexion reflex in the rat

Laird¹,

Hargreaves²,

Hill³

1993

British J Pharmacology

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“…Neonatal capsaicin treatment selectively destroys a subpopulation of DRG neurons, mainly those with small, unmyelinated primary afferent axons (Wall et al, 1982;Nagy et a]., 1983;Cervero et al, 1984). This loss of C fiber input to the dorsal horn results in an alteration in the processing of nociceptive information in the spinal cord (Hylden et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…Capsaicin, when administered neonatally. results in a selective destruction of a large subpopulation of small diameter, mainly unmyelinated primary afferents (Jancs6 et al, 1977;Wall et al, 1982;Nagy et al, 1983;Cervero et al, 1984;Harnmond and Ruda, 1989, I99 1). These unmyelinated axons include thosc that contain the peptides CGRP and SOM.…”

Section: Introductionmentioning

confidence: 99%

Quantification of axotomy‐induced alteration of neuropeptide mRNAs in dorsal root ganglion neurons with special reference to neuropeptide Y mRNA and the effects of neonatal capsaicin treatment

Noguchi

León

Nahin

et al. 1993

J of Neuroscience Research

134

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Alteration in mRNA expression in dorsal root ganglia (DRG) neurons encoding 5 neuropeptides was quantitatively compared in normal rats and in those neonatally treated with capsaicin, a selective neurotoxin which destroys a subpopulation of DRG neurons with unmyelinated axons. Adult rats received a unilateral transection of the sciatic nerve and were killed 7 days later. Oligonucleotide probes specific for the genes encoding neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), galanin (GAL), somatostatin (SOM), and calcitonin gene-related peptide (CGRP) were used for in situ hybridization and RNA blot analysis. Following the nerve cut, RNA blot analysis demonstrated a dramatic induction of NPY, VIP, and GAL mRNA levels from the undetectable constitutive level of expression. Conversely, CGRP and SOM mRNAs, which are constitutively expressed, were reduced 55% and 70%, respectively, following the nerve cut. A unimodal size distribution for neurons expressing NPY mRNA was determined, with a mean cross-sectional area of 1700 microns2 representing 24.4% of DRG neurons ipsilateral to the nerve cut. Neurons expressing VIP mRNA were mainly small sized, with a cross-sectional area of approximately 700 microns2, while those expressing GAL mRNA were both small (approximately 700 microns2) and medium (approximately 1,300 microns2) sized. The percentages of neurons expressing VIP or GAL mRNA were 19.9% and 33.7%, respectively. In neonatal capsaicin-treated rats, there was a 10% reduction in neurons expressing NPY mRNA, a 37% reduction for VIP, and a 27% for GAL mRNA compared to vehicle-treated rats after nerve cut. Capsaicin-sensitive neurons comprised 37% of CGRP neurons and 83% of SOM neurons. These observations suggest that NPY is primarily induced in myelinated primary afferent neurons, while VIP and GAL mRNA induction occurs in a mixed population, a sizeable percentage of which has unmyelinated axons. Additionally, SOM mRNA expression is associated mainly with unmyelinated primary afferents.

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“…Noxious stimulation or damage of internal organs also evokes severe pain and hyperalgesia (Cervero, 1994), but the extent of wind-up and other NMDA-mediated phenomenon in visceral nociceptive pathways and the possible contribution of these mechanisms to visceral pain and hyperalgesia has received very little attention. A previous study from this laboratory has shown that only 26 % of viscero-somatic dorsal horn neurones in the thoracic spinal cord show wind-up on repetitive stimulation of visceral unmyelinated afferents (Alarcon & Cervero, 1990), which differs markedly from the 50-70% of dorsal horn neurones found to wind-up in the lumbar spinal cord on repetitive stimulation of cutaneous unmyelinated afferents (Schouenborg & Sj6lund, 1983;Cervero, Schouenborg, Sjolund & Waddell, 1984). Thus, it is possible that wind-up may not be as prominent in visceral nociceptive pathways as it is in cutaneous nociceptive pathways and that alternative mechanisms could underlie the onset and maintenance of visceral pain and hyperalgesia.…”

mentioning

confidence: 88%

Excitability changes of somatic and viscero‐somatic nociceptive reflexes in the decerebrate‐spinal rabbit: role of NMDA receptors.

Laird

Rubia

Cerveró

1995

The Journal of Physiology

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Cutaneous inputs to dorsal horn neurones in adult rats treated at birth with capsaicin

Cited by 62 publications

References 25 publications

Effect of RP 67580, a non‐peptide neurokinin₁ receptor antagonist, on facilitation of a nociceptive spinal flexion reflex in the rat

Effect of RP 67580, a non‐peptide neurokinin₁ receptor antagonist, on facilitation of a nociceptive spinal flexion reflex in the rat

Quantification of axotomy‐induced alteration of neuropeptide mRNAs in dorsal root ganglion neurons with special reference to neuropeptide Y mRNA and the effects of neonatal capsaicin treatment

Excitability changes of somatic and viscero‐somatic nociceptive reflexes in the decerebrate‐spinal rabbit: role of NMDA receptors.

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Cutaneous inputs to dorsal horn neurones in adult rats treated at birth with capsaicin

Cited by 62 publications

References 25 publications

Effect of RP 67580, a non‐peptide neurokinin1 receptor antagonist, on facilitation of a nociceptive spinal flexion reflex in the rat

Effect of RP 67580, a non‐peptide neurokinin1 receptor antagonist, on facilitation of a nociceptive spinal flexion reflex in the rat

Quantification of axotomy‐induced alteration of neuropeptide mRNAs in dorsal root ganglion neurons with special reference to neuropeptide Y mRNA and the effects of neonatal capsaicin treatment

Excitability changes of somatic and viscero‐somatic nociceptive reflexes in the decerebrate‐spinal rabbit: role of NMDA receptors.

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Effect of RP 67580, a non‐peptide neurokinin₁ receptor antagonist, on facilitation of a nociceptive spinal flexion reflex in the rat

Effect of RP 67580, a non‐peptide neurokinin₁ receptor antagonist, on facilitation of a nociceptive spinal flexion reflex in the rat