Involvement of substance P and neurokinin-1 receptors in the hyperexcitability of dorsal horn neurons during development of acute arthritis in rat's knee joint

1995 ◽  
Vol 73 (4) ◽  
pp. 1574-1583 ◽  
Author(s):  
V. Neugebauer ◽  
F. Weiretter ◽  
H. G. Schaible
Keyword(s):  
Substance P ◽  
Knee Joint ◽  
Intravenous Administration ◽  
Initial Period ◽  
Receptive Fields ◽  
Neurokinin A ◽  
Mechanical Stimuli ◽  
Similar Reduction ◽  
Spinal Cord Neurons ◽  
Neurokinin 1

1. In anesthetized rats we studied the involvement of substance P and neurokinin-1 receptors in the generation and maintenance of hyperexcitability in spinal cord neurons, which develops in the course of an acute experimental inflammation in the knee. In all experiments one nociceptive neuron with knee input was identified, and the responses to mechanical stimuli and the receptive fields were monitored before and after induction of inflammation by the injections of kaolin and carrageenan into the knee joint. In 18 experiments either the specific antagonist at the neurokinin-1 receptor ionophoretically close to the neuron or intravenously during the injections of kaolin and carrageenan and in three periods of 15 min in the 95 min postkaolin (initial period of inflammation) to test their effects on the development of hyperexcitability. CP96,345 and CP96,344 were also administered after full development of inflammation to study their effects in hyperexcitable neurons. CP96,345 was ejected at currents that reduced or completely suppressed the effects of ionophoretically administered substance P but not those of neurokinin A, the agonist at neurokinin-2 receptors. 2. After the injections of kaolin and carrageenan into the knee joint, untreated control neurons (n = 8) developed hyperexcitability consisting of enhanced responses to noxious stimuli applied to the injected knee and the noninjected ankle, of an enhancement or induction of the responses to innocuous pressure applied to the joints and of an expansion of the receptive field. In eight neurons treated with ionophoretic administration of CP96,345 during the induction and initial period of inflammation, the development of hyperexcitability was not completely prevented but significantly attenuated. In comparison with the changes in the control neurons, the development of hyperexcitability was markedly reduced from the 2nd h up to 5 h postkaolin, but it was barely affected by CP96,345 within the 1st h postkaolin. Intravenous administration of CP96,345 in the initial period of inflammation produced a similar reduction of the development of hyperexcitability in another four neurons. The ionophoretic application of CP96,344 during and after induction of inflammation did not apparently impair the development of hyperexcitability (n = 6 neurons). 3. After development of inflammation and hyperexcitability, both the responses to innocuous and noxious pressure applied to the inflamed knee joint were reduced by the ionophoretic (n = 16 neurons) and intravenous administration (n = 9 neurons) of CP96,345 (tested 4.5-8 h postkaolin). Similarly, the responses to innocuous and noxious pressure applied to the noninflamed ankle were reduced by CP96,345 after inflammation had developed in the knee joint.(ABSTRACT TRUNCATED AT 400 WORDS)

Substance P-induced inflammation in the rat knee joint is mediated by neurokinin 1 (NK1) receptors

1993 ◽  
Vol 46 (1-2) ◽  
pp. 198-201 ◽  
Author(s):  
F.Y. Lam ◽  
W.R. Ferrell ◽  
D.T. Scott
Keyword(s):  
Substance P ◽  
Knee Joint ◽  
Nk1 Receptors ◽  
Neurokinin 1

Presence of NK1 receptors on a mucosal-like mast cell line, RBL-2H3 cells

1998 ◽  
Vol 76 (2) ◽  
pp. 188-193 ◽  
Author(s):  
Helen J Cooke ◽  
Paula Fox ◽  
Lisa Alferes ◽  
Charity C Fox ◽  
Seth A Wolfe, Jr.
Keyword(s):  
Mast Cell ◽  
Substance P ◽  
Binding Sites ◽  
Neurokinin A ◽  
Competition Binding ◽  
Polymerase Chain ◽  
Mast Cell Line ◽  
Neurokinin 1 ◽  
Receptor Agonists And Antagonists ◽  
Substance P Receptors

Reverse transcription - polymerase chain reaction of mRNA from rat RBL-2H3 cells yielded a 316 base pair band consistent with that predicted for the neurokinin-1 (NK1) receptor. Saturation and competition binding with 125I-labeled Bolton-Hunter substance P, substance P fragments, and a series of selective tachykinin receptor agonists and antagonists demonstrated that RBL-2H3 cells express high affinity binding sites for substance P on their surfaces with the kinetic and pharmacological properties of NK1 receptors. The pharmacology of these 125I-labeled substance P binding sites was (from most to least potent) [Sar9,Met(O2)11]substance P > substance P 4-11 >> GR82334 >> MEN 10,376. However, substance P 1-4, substance P 8-11, substance P 9-11, and [Trp7, beta -Ala8]neurokinin A 4-10 failed to compete for binding. The metabolically stable NK1 receptor agonist, [Sar9,Met(O2)11] substance P, caused a 49% increase in 5-hydroxytryptamine release above basal levels. The results demonstrate the presence of functional NK1 receptors on RBL-2H3 cells, a mucosal-like mast cell line.Key words: substance P, receptors, mast cells, 5-hydroxytryptamine, tachykinins.

Evidence for a central component in the sensitization of spinal neurons with joint input during development of acute arthritis in cat's knee

1990 ◽  
Vol 64 (1) ◽  
pp. 299-311 ◽  
Author(s):  
V. Neugebauer ◽  
H. G. Schaible
Keyword(s):  
Spinal Cord ◽  
Knee Joint ◽  
Mechanical Stimulation ◽  
Receptive Fields ◽  
Lumbar Spinal Cord ◽  
Mechanical Stimuli ◽  
Spinal Neurons ◽  
Deep Tissue ◽  
Lumbar Spinal ◽  
Stimulation Of

1. In the spinalized cat, nociceptive spinal neurons with knee input show enhanced responses to mechanical stimulation of that joint once an inflammation has developed in the knee. Enhanced responses may result from increased afferent inflow as well as from modifications of the nociceptive processing within the spinal cord. To examine the significance of these components, we tested in 30 chloralose-anesthetized, spinalized cats whether, during development of arthritis, changes of responsiveness in spinal neurons are restricted to stimulation of the inflamed joint or whether responsiveness in these neurons is altered in general. While continuously recording from a neuron, we injected kaolin and carrageenan into one knee and tested the responses to mechanical stimuli applied to the joint and to regions adjacent to and remote from the knee during the developing arthritis. In addition, in six cats we monitored the neurons' responses to electrical stimulation of the sural nerves and the rostral lumbar spinal cord. 2. Of 32 neurons in laminae VI, VII, and VIII of the lumbar spinal cord, 15 ascending and eight nonascending cells were driven by mechanical stimulation of one or both knee joint(s). Nine of these were nociceptive specific (NS), responding exclusively or predominantly to noxious compression of the knee and other deep tissue, and 12 were wide-dynamic-range (WDR) cells with graded responses to gentle and noxious stimuli applied to the knee joint(s), deep tissue, and skin. Two neurons with high ongoing discharges had some excitatory joint input but showed marked inhibition by most stimuli used (INH neurons). The majority of the neurons had receptive fields on both legs. Nine of the 32 neurons had no input from the knee(s). 3. All 23 neurons with joint input became sensitive or more responsive to movements and gentle compression of the inflamed knee once the inflammation had developed. In general, these neurons also showed enhanced responses to compression of the adjacent muscles in thigh and lower leg. In 20 neurons, response properties were even altered for stimuli applied to regions remote from the inflamed joint, including the contralateral leg in 18 cases. We found expansion of initially restricted receptive fields (mainly in NS cells), enhancement of preexisting responses, and/or lowering of threshold to mechanical stimuli applied to these regions; few neurons developed inhibitory reactions.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Substance P (Neurokinin-1) and Neurokinin A (Neurokinin-2) Receptor Gene and Protein Expression in the Healthy and Inflamed Human Intestine

2000 ◽  
Vol 157 (5) ◽  
pp. 1511-1522 ◽  
Author(s):  
Daniela Renzi ◽  
Beatrice Pellegrini ◽  
Francesco Tonelli ◽  
Calogero Surrenti ◽  
Antonio Calabrò
Keyword(s):  
Substance P ◽  
Protein Expression ◽  
Receptor Gene ◽  
Neurokinin A ◽  
Human Intestine ◽  
Gene And Protein Expression ◽  
Neurokinin 1

N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists block the hyperexcitability of dorsal horn neurons during development of acute arthritis in rat's knee joint

1993 ◽  
Vol 70 (4) ◽  
pp. 1365-1377 ◽  
Author(s):  
V. Neugebauer ◽  
T. Lucke ◽  
H. G. Schaible
Keyword(s):  
Dorsal Horn ◽  
Time Course ◽  
Receptive Fields ◽  
Nmda Antagonist ◽  
Mechanical Stimuli ◽  
Nmda Antagonists ◽  
Spinal Cord Neurons ◽  
Intravenous Injections ◽  
Mechanical Threshold ◽  
Before And After

1. In 22 anesthetized rats we studied the involvement of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the generation and maintenance of hyperexcitability in spinal cord neurons with knee input that develops in the course of an acute inflammation in the knee. In all experiments one neuron with knee input was identified, and the responses to mechanical stimuli and the receptive fields were monitored before and after induction of inflammation by the intra-articular injections of kaolin and carrageenan into the joint cavity. In most experiments multibarrel electrodes were used to administer specific NMDA and non-NMDA antagonists ionophoretically close to the neuron to test their effects on the inflammation-evoked changes. 2. Six neurons in the deep dorsal horn in six rats were used to establish the time course of the development of hyperexcitability in the untreated animal. In control periods of up to 3 h, the responses to mechanical stimuli and the receptive fields were stable. After induction of inflammation, the neurons developed increased responsiveness to mechanical stimuli applied to the injected knee but also to mechanical stimuli applied to the ipsilateral ankle and paw (including a reduction in the mechanical threshold in nociceptive specific neurons). The receptive fields expanded in five out of six neurons. The changes of responsiveness occurred mainly in the 2nd to 3rd h after the injection of kaolin. 3. In four rats three to four intravenous injections of the NMDA antagonist ketamine (2 mg/kg) were given during the injections of kaolin and carrageenan and in the following periods (up to 101 min postkaolin). During this treatment none of the four neurons exhibited the changes of responsiveness that were usually seen in control animals, although swelling of the knee developed in the same fashion as in control rats. Similarly, the generation of hyperexcitability was prevented when the NMDA antagonists ketamine and DL-2-amino-5-phosphonovalerate (AP5) were administered ionophoretically (ketamine in 4, AP5 in 2 rats) during the injections of kaolin and carrageenan and up to 100 min postkaolin. The doses of ketamine and AP5 were sufficient to reduce the responses to NMDA, whereas the responses to the non-NMDA agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were not influenced. 4. The ionophoretic application of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) during the injections of the kaolin and carrageenan and up to 103 min postkaolin also prevented the generation of hyperexcitability in six neurons in six rats.(ABSTRACT TRUNCATED AT 400 WORDS)

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