The Effects of Substance P and Baclofen on Motoneurones of Isolated Spinal Cord of the Newborn Rat

1980 ◽  
Vol 89 (1) ◽  
pp. 201-214
Author(s):  
MASANORI OTSUKA ◽  
MITSUHIKO YANAGISAWA
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Ventral Root ◽  
Spinal Reflexes ◽  
Monosynaptic Reflex ◽  
Artificial Cerebrospinal Fluid ◽  
Site Of Action ◽  
Spinal Neurones ◽  
Depolarizing Agents ◽  
Root Stimulation

The effects of substance P (SP) and baclofen were studied in the isolated spinal cord of newborn rats. Potential changes generated in motoneurones were recorded extracellularly from the ventral root (L3-L5). When SP (8 × 10−5M) was introduced into the bath, the depolarization of motoneurones began with a delay of 1·1 s. A large part of this delay can be explained as a time needed for SP to reach the site of action on spinal neurones. When the preparation was perfused with artificial cerebrospinal fluid (CSF) containing low Ca (0·1 mM) and high Mg (1·6-3·5 mM), the spinal reflexes induced by dorsal root stimulation and recorded from the corresponding ventral root were completely abolished. The depolarizing action of SP (10−7M) on the motoneurones was potentiated in the low-Ca medium, suggesting that SP acts directly on the motoneurones. Baclofen at 10−6M depressed the monosynaptic reflex by about 75%. The SP-induced depolarization of motoneurones was greatly depressed by baclofen in both normal and 0·1 mM-Ca mediums. The effects of baclofen (10−6M) on the responses to various depolarizing agents were compared with that on the response to SP in artificial CSF containing 0·1 mM-Ca and 1·6-2 mM-Mg. The SP response was reduced by about 80%, whereas the responses to acetylcholine and glycine were not appreciably affected, and those to L-glutamate, GABA and noradrenaline were depressed by 10–22% by baclofen. These results suggest that baclofen blocks transmission at certain primary afferent synapses by antagonizing the action of SP that is released as a transmitter.

scholarly journals Effects of Baclofen on Spinal Reflexes and Persistent Inward Currents in Motoneurons of Chronic Spinal Rats With Spasticity

2004 ◽  
Vol 92 (5) ◽  
pp. 2694-2703 ◽  
Author(s):  
Y. Li ◽  
X. Li ◽  
P. J. Harvey ◽  
D. J. Bennett
Keyword(s):  
Spinal Cord ◽  
Ventral Root ◽  
Spinal Reflexes ◽  
Monosynaptic Reflex ◽  
Persistent Inward Currents ◽  
Inward Currents ◽  
Muscle Spasms ◽  
Acute Spinal Rats ◽  
Chronic Spinal Rats ◽  
Higher Doses

In the months after spinal cord injury, motoneurons develop large voltage-dependent persistent inward currents (PICs) that cause sustained reflexes and associated muscle spasms. These muscle spasms are triggered by any excitatory postsynaptic potential (EPSP) that is long enough to activate the PICs, which take >100 ms to activate. The PICs are composed of a persistent sodium current (Na PIC) and a persistent calcium current (Ca PIC). Considering that Ca PICs have been shown in other neurons to be inhibited by baclofen, we tested whether part of the antispastic action of baclofen was to reduce the motoneuron PICs as opposed to EPSPs. The whole sacrocaudal spinal cord from acute spinal rats and spastic chronic spinal rats (with sacral spinal transection 2 mo previously) was studied in vitro. Ventral root reflexes were recorded in response to dorsal root stimulation. Intracellular recordings were made from motoneurons, and slow voltage ramps were used to measure PICs. Chronic spinal rats exhibited large monosynaptic and long-lasting polysynaptic ventral root reflexes, and motoneurons had associated large EPSPs and PICs. Baclofen inhibited these reflexes at very low doses with a 50% inhibition (EC50) of the mono- and polysynaptic reflexes at 0.26 ± 0.07and 0.25 ± 0.09 (SD) μM, respectively. Baclofen inhibited the monosynaptic reflex in acute spinal rats at even lower doses (EC50 = 0.18 ± 0.02 μM). In chronic (and acute) spinal rats, all reflexes and EPSPs were eliminated with 1 μM baclofen with little change in motoneuron properties (PICs, input resistance, etc), suggesting that baclofen's antispastic action is presynaptic to the motoneuron. Unexpectedly, in chronic spinal rats higher doses of baclofen (20–30 μM) significantly increased the total motoneuron PIC by 31.6 ± 12.4%. However, the Ca PIC component (measured in TTX to block the Na PIC) was significantly reduced by baclofen. Thus baclofen increased the Na PIC and decreased the Ca PIC with a net increase in total PIC. By contrast, when a PIC was induced by 5-HT (10–30 μM) in motoneurons of acute spinal rats, baclofen (20–30 μM) significantly decreased the PIC by 38.8 ± 25.8%, primarily due to a reduction in the Ca PIC (measured in TTX), which dominated the total PIC in these acute spinal neurons. In summary, baclofen does not exert its antispastic action postsynaptically at clinically achievable doses (<1 μM), and at higher doses (10–30 μM), baclofen unexpectedly increases motoneuron excitability (Na PIC) in chronic spinal rats.

Motoneuron properties during motor inhibition produced by microinjection of carbachol into the pontine reticular formation of the decerebrate cat

1987 ◽  
Vol 57 (4) ◽  
pp. 1118-1129 ◽  
Author(s):  
F. R. Morales ◽  
J. K. Engelhardt ◽  
P. J. Soja ◽  
A. E. Pereda ◽  
M. H. Chase
Keyword(s):  
Spinal Cord ◽  
Motor Activity ◽  
Reticular Formation ◽  
Input Resistance ◽  
Ventral Root ◽  
Monosynaptic Reflex ◽  
Pontine Reticular Formation ◽  
Active Sleep ◽  
Decerebrate Cat ◽  
Inhibitory Postsynaptic Potentials

It is well established that cholinergic agonists, when injected into the pontine reticular formation in cats, produce a generalized suppression of motor activity (1, 3, 6, 14, 18, 27, 33, 50). The responsible neuronal mechanisms were explored by measuring ventral root activity, the amplitude of the Ia-monosynaptic reflex, and the basic electrophysiological properties of hindlimb motoneurons before and after carbachol was microinjected into the pontine reticular formation of decerebrate cats. Intrapontine microinjections of carbachol (0.25-1.0 microliter, 16 mg/ml) resulted in the tonic suppression of ventral root activity and a decrease in the amplitude of the Ia-monosynaptic reflex. An analysis of intracellular records from lumbar motoneurons during the suppression of motor activity induced by carbachol revealed a considerable decrease in input resistance and membrane time constant as well as a reduction in motoneuron excitability, as evidenced by a nearly twofold increase in rheobase. Discrete inhibitory postsynaptic potentials were also observed following carbachol administration. The changes in motoneuron properties (rheobase, input resistance, and membrane time constant), as well as the development of discrete inhibitory postsynaptic potentials, indicate that spinal cord motoneurons were postsynaptically inhibited following the pontine administration of carbachol. In addition, the inhibitory processes that arose after carbachol administration in the decerebrate cat were remarkably similar to those that are present during active sleep in the chronic cat. These findings suggest that the microinjection of carbachol into the pontine reticular formation activates the same brain stem-spinal cord system that is responsible for the postsynaptic inhibition of alpha-motoneurons that occurs during active sleep.

Use of NK1 receptor antagonists in the exploration of physiological functions of substance P and neurokinin A

1995 ◽  
Vol 73 (7) ◽  
pp. 903-907 ◽  
Author(s):  
M. Qtsuka ◽  
K. Yoshioka ◽  
M. Yanagisawa ◽  
H. Suzuki ◽  
F.-Y. Zhao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Substance P ◽  
Guinea Pig ◽  
Saphenous Nerve ◽  
Ventral Root ◽  
Neonatal Rat ◽  
Neurokinin A ◽  
Receptor Antagonists ◽  
Stimulation Of

Tachykinin NK1 receptor antagonists were used to explore the physiological functions of substance P (SP) and neurokinin A (NKA). Pharmacological profiles of three NK1 receptor antagonists, GR71251, GR82334, and RP 67580, were examined in the isolated spinal cord preparation of the neonatal rat. These tachykinin receptor antagonists exhibited considerable specificities and antagonized the actions of both SP and NKA to induce the depolarization of ventral roots. Electrical stimulation of the saphenous nerve with C-fiber strength evoked a depolarization lasting about 30 s of the ipsilateral L3 ventral root. This response, which is referred to as saphenous-nerve-evoked slow ventral root potential (VRP), was depressed by these NK1 receptor antagonists. In contrast, the saphenous-nerve-evoked slow VRP was potentiated by application of a mixture of peptidase inhibitors, including thiorphan, actinonin, and captopril in the presence of naloxone, but not after further addition of GR71251. Likewise, in the isolated coeliac ganglion of the guinea pig, electrical stimulation of the mesenteric nerves evoked in some ganglionic cells slow excitatory postsynaptic potentials (EPSPs), which were depressed by GR71251 and potentiated by peptidase inhibitors. These results further support the notion that SP and NKA serve as neurotransmitters producing slow EPSPs in the neonatal rat spinal cord and guinea pig prevertebral ganglia.Key words: substance P, neurokinin A, neurotransmitter, tachykinin antagonist, spinal cord.

Neuropeptide-Mediated Facilitation and Inhibition of Sensory Inputs and Spinal Cord Reflexes in the Lamprey

1999 ◽  
Vol 81 (4) ◽  
pp. 1730-1740 ◽  
Author(s):  
Maria Ullström ◽  
David Parker ◽  
Erik Svensson ◽  
Sten Grillner
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Motor Neurons ◽  
Ventral Root ◽  
Sensory Level ◽  
Synaptic Inputs ◽  
Sensory Inputs ◽  
Reflex Responses ◽  
Spinal Cord Reflexes ◽  
Root Responses

Neuropeptide-mediated facilitation and inhibition of sensory inputs and spinal cord reflexes in the lamprey. The effects of neuromodulators present in the dorsal horn [tachykinins, neuropeptide Y (NPY), bombesin, and GABAB agonists] were studied on reflex responses evoked by cutaneous stimulation in the lamprey. Reflex responses were elicited in an isolated spinal cord preparation by electrical stimulation of the attached tail fin. To be able to separate modulator-induced effects at the sensory level from that at the motor or premotor level, the spinal cord was separated into three pools with Vaseline barriers. The caudal pool contained the tail fin. Neuromodulators were added to this pool to modulate sensory inputs evoked by tail fin stimulation. The middle pool contained high divalent cation or low calcium Ringer to block polysynaptic transmission and thus limit the input to the rostral pool to that from ascending axons that project through the middle pool. Ascending inputs and reflex responses were monitored by making intracellular recordings from motor neurons and extracellular recordings from ventral roots in the rostral pool. The tachykinin neuropeptide substance P, which has previously been shown to potentiate sensory input at the cellular and synaptic levels, facilitated tail fin-evoked synaptic inputs to neurons in the rostral pool and concentration dependently facilitated rostral ventral root activity. Substance P also facilitated the modulatory effects of tail fin stimulation on ongoing locomotor activity in the rostral pool. In contrast, NPY and the GABAB receptor agonist baclofen, both of which have presynaptic inhibitory effects on sensory afferents, reduced the strength of ascending inputs and rostral ventral root responses. We also examined the effects of the neuropeptide bombesin, which is present in sensory axons, at the cellular, synaptic, and reflex levels. As with substance P, bombesin increased tail fin stimulation-evoked inputs and ventral root responses in the rostral pool. These effects were associated with the increased excitability of slowly adapting mechanosensory neurons and the potentiation of glutamatergic synaptic inputs to spinobulbar neurons. These results show the possible behavioral relevance of neuropeptide-mediated modulation of sensory inputs at the cellular and synaptic levels. Given that the types and locations of neuropeptides in the dorsal spinal cord of the lamprey show strong homologies to that of higher vertebrates, these results are presumably relevant to other vertebrate systems.

scholarly journals Interactions between Dorsal and Ventral Root Stimulation on the Generation of Locomotor-Like Activity in the Neonatal Mouse Spinal Cord

eNeuro ◽  
2016 ◽  
Vol 3 (3) ◽  
pp. ENEURO.0101-16.2016 ◽  
Author(s):  
Avinash Pujala ◽  
Dvir Blivis ◽  
Michael J. O’Donovan
Keyword(s):  
Spinal Cord ◽  
Ventral Root ◽  
Neonatal Mouse ◽  
Mouse Spinal Cord ◽  
Root Stimulation

scholarly journals Comparison of the Effects on Spinal Reflexes of Acetylsalicylate and Metamizol in Spinalized and Normal Rats

2005 ◽  
Vol 48 (3-4) ◽  
pp. 149-152
Author(s):  
Osman Genç ◽  
Sebahat Turgut ◽  
Günfer Turgut ◽  
Selim Kortunay
Keyword(s):  
Spinal Cord ◽  
Arachidonic Acid ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Ventral Root ◽  
Spinal Reflexes ◽  
Reflex Response ◽  
Antiinflammatory Drugs ◽  
Lumbosacral Region ◽  
Adult Rats ◽  
Stimulation Of

The effects of nonsteroidal antiinflammatory drugs, acetylsalicylate and metamizol, on spinal monosynaptic reflexes were investigated in spinalized and normal rats. Adult rats (n=36) weighing 150–200 g were anesthetized with ketamine and artificially ventilated. Half of rats were spinalized at C1 level. A laminectomy was performed in the lumbosacral region. Following electrical stimulation of the sciatic nerve by single pulses, reflex potentials were recorded from the ipsilateral L5 ventral root. Acetylsalicylate was administered orally (100 mg/kg for both spinalized and normal rats). Metamizol was administered intramuscularly (15 mg/kg for both spinalized and normal rats). These drug administrations significantly decreased the amplitude of reflex response in all groups (p<0.05). These data verify that observed inhibition by acetylsalicylicate and metamizol may be at the level of spinal cord. Also we suggested that the cyclooxygenase products of arachidonic acid may play an important role in regulating the reflex potential.

Substance P selectively blocks excitation of Renshaw cell by acetylcholine

1977 ◽  
Vol 55 (4) ◽  
pp. 958-961 ◽  
Author(s):  
K. Krnjević ◽  
Dušan Lekić
Keyword(s):  
Amino Acids ◽  
Substance P ◽  
Diffusion Barriers ◽  
Ventral Root ◽  
Renshaw Cells ◽  
Renshaw Cell ◽  
Small Doses ◽  
Higher Doses ◽  
Root Stimulation ◽  
Synaptic Responses

In cats, under Dial anaesthesia, Renshaw cells were excited by microiontophoretic applications of acetylcholine (ACh), aspartate, and glutamate. Substance P, in small doses (10–30 nA), selectively abolished the responses to ACh, leaving the discharges evoked by the amino acids unchanged or enhanced. Higher doses (> 50 nA) depressed all responses, but those evoked by amino acids went down last and recovered sooner. By contrast, neither synaptic responses to ventral root stimulation nor spontaneous discharges were affected by substance P, presumably owing to the high efficacy of synaptic transmission and the presence of diffusion barriers around junctional sites.

Dopamine exerts activation-dependent modulation of spinal locomotor circuits in the neonatal mouse

2012 ◽  
Vol 108 (12) ◽  
pp. 3370-3381 ◽  
Author(s):  
Jennifer M. Humphreys ◽  
Patrick J. Whelan
Keyword(s):  
Spinal Cord ◽  
Feedback Loops ◽  
Ventral Root ◽  
Neonatal Mouse ◽  
Network Activity ◽  
Mouse Spinal Cord ◽  
Network Function ◽  
Renshaw Cell ◽  
Root Stimulation ◽  
Excitatory Drive

Monoamines can modulate the output of a variety of invertebrate and vertebrate networks, including the spinal cord networks that control walking. Here we examined the multiple changes in the output of locomotor networks induced by dopamine (DA). We found that DA can depress the activation of locomotor networks in the neonatal mouse spinal cord following ventral root stimulation. By examining disinhibited rhythms, where the Renshaw cell pathway was blocked, we found that DA depresses a putative recurrent excitatory pathway that projects onto rhythm-generating circuitry of the spinal cord. This depression was D2 but not D1 receptor dependent and was not due exclusively to depression of excitatory drive to motoneurons. Furthermore, the depression in excitation was not dependent on network activity. We next compared the modulatory effects of DA on network function by focusing on a serotonin and a N-methyl-dl-aspartate-evoked rhythm. In contrast to the depressive effects on a ventral root-evoked rhythm, we found that DA stabilized a drug-evoked rhythm, reduced the frequency of bursting, and increased amplitude. Overall, these data demonstrate that DA can potentiate network activity while at the same time reducing the gain of recurrent excitatory feedback loops from motoneurons onto the network.

Depression of Nociceptive Sensory Activity in the Rat Spinal Cord Due to the Intrathecal Administration of Drugs: Effect of Diazepam

Neurosurgery ◽  
1984 ◽  
Vol 15 (6) ◽  
pp. 917-920 ◽  
Author(s):  
Ilmar Jurna
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Nerve Fibers ◽  
Afferent Nerve ◽  
Spinal Reflexes ◽  
Sensory Response ◽  
Motor Responses ◽  
Afferent Nerve Fibers ◽  
C Fiber ◽  
Stimulation Of

Abstract The intrathecal (i.t.) administration of morphine inhibits nociceptive motor responses and activity in ascending axons evoked by stimulation of nociceptive afferent nerve fibers (nociceptive sensory response) in the rat. The i.t. administration of cholecystokinin octapeptide and ceruletide inhibits nociceptive motor responses, but does not affect ascending nociceptive activity. This shows that drug-induced depression of nociceptive motor responses is not always associated with depression of the nociceptive sensory response of the spinal cord. The microiontophoretic application of substance P excites single dorsal horn neurons that respond to noxious stimulation, whereas the i.t. administration of substance P inhibits both nociceptive motor and sensory responses. Thus, the results obtained from the i.t. administration of a drug may differ from those obtained from its application to single spinal neurons. Diazepam inhibits spinal reflexes and may reduce pain sensation in humans. To assess whether a spinal action is involved in the pain-relieving effect of diazepam, experiments were carried out on spinalized rats in which activity evoked by the stimulation of nociceptive and nonnociceptive afferent nerve fibers of the sural nerve was recorded from single ascending axons below the site of spinal cord transection. Diazepam, 20 ųg i.t., reduced activity evoked by afferent A delta and C fiber stimulation and by stimulation of afferent A beta fibers. The depressant effect caused by diazepam, 2 mg/kg i.v., on C fiber-evoked ascending activity was reduced by the i.t. injection of the benzodiazepine antagonist, Ro 15-1788 (40 ųg), an imidazodiazepine. It is concluded that the depression by diazepam of C fiber-evoked ascending activity contributes to pain relief caused by the drug.

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