Modulation of spinal cord transmission by changes in extracellular K+ activity and extracellular volume

1987 ◽  
Vol 65 (5) ◽  
pp. 1058-1066 ◽  
Author(s):  
Eva Syková

The neuronal activity in spinal cord in response to electrical or adequate stimulation of afferent fibres increases extracellular K+ activity. The increase during a stimulation can reach 9–10 mM (so-called ceiling level) and persists for some time even when a stimulation is discontinued. The activation of a neuronal Na–K pump is a limiting factor in stimulation-evoked increase in extracellular K+ activity and in the time course of its recovery to the resting level. Drugs that affect either the neuronal activity (picrotoxin, strychnine, GABA, 5-HT) or activity of Na–K ATPase (oubain, naloxone, morphine, enkephalins) substantially change the K+ transience. Repetitive electrical stimulation of low threshold cutaneous afferents at frequency 1–100 Hz induced transient shrinkage of extracellular space in spinal dorsal horns by 5–75%. The increase in extracellular K+ activity depolarizes the membranes of neurones, glial cells, and primary afferent fibres and may eventually lead to either facilitation or inhibition of synaptic transmission. It is also suggested that the transient poststimulation changes in extracellular volume may alter synaptic potency in spinal cord.

1975 ◽  
Vol 38 (5) ◽  
pp. 1181-1195 ◽  
Author(s):  
P. Rudomin ◽  
R. Nunez ◽  
J. Madrid

1. In the unanesthetized spinal cord, conditioning stimulation of low-threshold afferents (below 1.3 times threshold strength) in the biceps semitendinosus (BST) nerve often reduced the peak amplitude of the monosynaptic Ia EPSPs evoked in gastrocnemius motoneurons without affecting the monosynaptic component of the EPSPs evoked by stimulation of the ipsilateral ventral funiculus (VF) in the thoracic cord. 2. Volleys to the BST nerve comprising higher threshold afferents (usually above 1.4 times threshold strength) reduced the peak amplitude of the monosynaptic Ia and VF EPSPs and shortened their falling phase. 3. Conditioning volleys to low-threshold cutaneous afferents often increased the Ia-EPSP peak amplitude, sometimes without affecting the monosynaptic component of the VF EPSP. 4. In most cases the Ia nd VF monosynaptic EPSPs elicited in a given motoneuron summated nonlinearly. The amount of nonlinear summation between Ia and VF monosynaptic EPSPs was often reduced by low-threshold BST conditioning volleys. These observations suggest that in many instances, both species of fibers end in "electrotonically close" synaptic loci over the motoneuron surface. Therefore, amplitude changes of monosynaptic Ia EPSPs produced by conditioning afferent volleys without concomitant changes of monosynaptic VF EPSPs do not appear to result from postsynaptic remote conductance changes and may be attributed to a presynaptic mechanism. 5. At the time of occurrence of the Ia and VF monosynaptic EPSP the variance of the motoneuron membrane potential may be increased above base-line levels with a time course approximately matching the EPSP itself. Conditioning stimulation of BST afferents usually reduced Ia EPSP variance, often without affecting or even increasing the variance of the monosynaptic VF EPSPs. These observations provide additional evidence that Ia EPSP variability is introduced, at least in part, through the segmental pathways mediating primary afferent depolarization. 6. The possibility of a differential control of the information flow transmitted through two independent channels converging on a given cell ensemble is discussed.


2011 ◽  
Vol 14 (5) ◽  
pp. 583-597 ◽  
Author(s):  
Friederike Knerlich-Lukoschus ◽  
Beata von der Ropp-Brenner ◽  
Ralph Lucius ◽  
Hubertus Maximilian Mehdorn ◽  
Janka Held-Feindt

Object Central neuropathic pain is a frequent challenging complication after spinal cord injury (SCI), and specific therapeutic approaches remain elusive. The purpose of the present investigations was to identify potential key mediators of these pain syndromes by analyzing detailed expression profiles of important chemokines in an experimental SCI paradigm of posttraumatic neuropathic pain in rats. Methods Expression of CCR1, CCL3(MIP-1α), CXCR4, and CXCL12(SDF-1α) was investigated in parallel with behavioral testing for mechanical and thermal nociceptive thresholds after standardized SCI; 100-kdyn (moderate injury) and 200-kdyn (severe injury) force-defined thoracic spinal cord contusion lesions were applied via an Infinite Horizon Impactor at the T-9 level. Sham controls received laminectomies. Hindlimb locomotor function as well as mechanical and thermal sensitivities were monitored weekly by standardized behavioral testing after SCI. Chemokine expression was analyzed by real-time reverse transcriptase polymerase chain reaction in the early (7 days postoperatively) and late (42 days postoperatively) time courses after SCI, and immunohistochemical analysis (anatomical and quantitative) was performed 2, 7, 14, and 42 days after lesioning. Double staining with cellular markers and pain-related peptides (substance P and CGRP) or receptors (TRPV-1, TRPV-2, VRL-1, and TLR-4) was performed. Based on data obtained from behavioral testing, quantified immunohistochemical chemokine expressions in individual animals were correlated with the respective mechanical and thermal sensitivity thresholds 6 weeks after SCI. Results After 200-kdyn lesions, the animals exhibited prolonged reduction in their nociceptive thresholds, while 100-kdyn groups showed pain-related behaviors only in the early time course after SCI. Investigated chemokines were widely induced after SCI, involving cervical, thoracic, and lumbar spinal cord levels far beyond the lesion core. CCR1 and CCL3 were induced significantly in the dorsal horns 2 days after lesioning and remained at high levels after SCI with significantly higher intensities after 200-kdyn than 100-kdyn contusions. CXCR4 and CXCL12 levels continuously increased from 2 to 42 days after moderate and severe lesions. Additionally, chemokines were induced significantly in dorsal columns, with highest density levels 42 days after 200-kdyn lesions. In dorsal horns, CCR1 was coexpressed with TRPV-1 while CXCR4 and CXCL12 were partially coexpressed with substance P and CGRP. In dorsal columns, CCL3/CCR1 colabeled with GFAP, TRPV-2, TRPV-1, TLR-4; CXCR4/CXCL12 coexpressed with GFAP, CD68/ED1, and TLR4. Chemokine immunoreactivity density levels, especially CCL3 and its receptor, correlated in part significantly with nociceptive thresholds. Conclusions The authors report lesion grade–dependent upregulation of different chemokines/chemokine receptors after spinal cord contusion lesions in pain-processing spinal cord regions in a clinically relevant model of traumatic SCI in rats. Prolonged chemokine induction further correlated with below-level pain development in the delayed time course after severe SCI and was coexpressed with pain-associated peptides and receptors, suggesting that chemokines play a crucial role in chronic central pain mechanisms after SCI.


1978 ◽  
Vol 202 (1148) ◽  
pp. 417-421 ◽  

Motoneurons were directly visualized with Nomarski optics in slices prepared from new born rat spinal cord. Intracellular recordings from these neurons showed spontaneous potentials, probably triggered by inter-neuronal activity. Action potentials could also be evoked by direct intracellular stimulation of the motoneurons. Iontophoretically applied L-glutamate caused a fast depolarization of the motoneuronal membrane. Considerable differences in local sensitivity to L-glutamate were found on the surface of the motoneuron.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Chun-Yen Chen ◽  
Chao-Nan Lin ◽  
Rey-Shyong Chern ◽  
Yu-Chuan Tsai ◽  
Yung-Hsien Chang ◽  
...  

Aquapunctureis a modified acupuncture technique and it is generally accepted that it has a greater therapeutic effect than acupuncture because of the combination of the acupoint stimulation and the pharmacological effect of the drugs. However, to date, the mechanisms underlying the effects ofaquapunctureremain unclear. We hypothesized that both the change in the local spatial configuration and the substrate stimulation ofaquapuncturewould activate neuronal signaling. Thus, bee venom, normal saline, and vitamins B1 and B12 were injected into a Zusanli (ST36) acupoint as substrate ofaquapuncture, whereas a dry needle was inserted into ST36 as a control. Afteraquapuncture, activated neurons expressing Fos protein were mainly observed in the dorsal horn of the spinal cord in lumbar segments L3–5, with the distribution nearly identical among all groups. However, the bee venom injection induced significantly more Fos-expressing neurons than the other substrates. Based on these data, we suggest that changes in the spatial configuration of the acupoint activate neuronal signaling and that bee venom may further strengthen this neuronal activity. In conclusion, the mechanisms for the effects ofaquapunctureappear to be the spatial configuration changes occurring within the acupoint and the ability of injected substrates to stimulate neuronal activity.


1981 ◽  
Vol 3 (1) ◽  
pp. 195-209 ◽  
Author(s):  
Ronald J. Ignelzi ◽  
Judith K. Nyquist ◽  
William J. Tighe

2004 ◽  
Vol 91 (5) ◽  
pp. 2247-2258 ◽  
Author(s):  
D. J. Bennett ◽  
L. Sanelli ◽  
C. L. Cooke ◽  
P. J. Harvey ◽  
M. A. Gorassini

Following chronic sacral spinal cord transection in rats the affected tail muscles exhibit marked spasticity, with characteristic long-lasting tail spasms evoked by mild stimulation. The purpose of the present paper was to characterize the long-lasting reflex seen in tail muscles in response to electrical stimulation of the tail nerves in the awake spastic rat, including its development with time and relation to spasticity. Before and after sacral spinal transection, surface electrodes were placed on the tail for electrical stimulation of the caudal nerve trunk (mixed nerve) and for recording EMG from segmental tail muscles. In normal and acute spinal rats caudal nerve trunk stimulation evoked little or no EMG reflex. By 2 wk after injury, the same stimulation evoked long-lasting reflexes that were 1) very low threshold, 2) evoked from rest without prior EMG activity, 3) of polysynaptic latency with >6 ms central delay, 4) about 2 s long, and 5) enhanced by repeated stimulation (windup). These reflexes produced powerful whole tail contractions (spasms) and developed gradually over the weeks after the injury (≤52 wk tested), in close parallel to the development of spasticity. Pure low-threshold cutaneous stimulation, from electrical stimulation of the tip of the tail, also evoked long-lasting spastic reflexes, not seen in acute spinal or normal rats. In acute spinal rats a strong C-fiber stimulation of the tip of the tail (20 × T) could evoke a weak EMG response lasting about 1 s. Interestingly, when this C-fiber stimulation was used as a conditioning stimulation to depolarize the motoneuron pool in acute spinal rats, a subsequent low-threshold stimulation of the caudal nerve trunk evoked a 300–500 ms long reflex, similar to the onset of the long-lasting reflex in chronic spinal rats. A similar conditioned reflex was not seen in normal rats. Thus there is an unusually long low-threshold polysynaptic input to the motoneurons (pEPSP) that is normally inhibited by descending control. This pEPSP is released from inhibition immediately after injury but does not produce a long-lasting reflex because of a lack of motoneuron excitability. With chronic injury the motoneuron excitability is increased markedly, and the pEPSP then triggers sustained motoneuron discharges associated with long-lasting reflexes and muscle spasms.


1985 ◽  
Vol 54 (5) ◽  
pp. 1167-1177 ◽  
Author(s):  
L. A. Ritz ◽  
J. L. Culberson ◽  
P. B. Brown

We have explored the somatotopic organization of the two cat spinal cord regions where the dorsal horns are fused (i.e., continuous across the midline): the caudal and thoracic segments. We have mapped the low-threshold component of dorsal horn cell receptive fields (RFs) in these segments and have charted the locations of dorsal root low-threshold mechanoreceptive dermatomes. We also have determined the projections of caudal and thoracic dorsal roots to laminae III and IV by using degeneration techniques. The dorsal skin of the tail or thorax is represented laterally, and ventral skin is represented at the midline, in the fused dorsal horns. Many caudal and thoracic dorsal horn units had RFs that crossed the dorsal or ventral midline of the skin; these units were encountered near the edges or the midline, respectively, of the fused dorsal horns. The tail is fully represented within dorsal root dermatomes S3 to Ca5. Roots more caudal than Ca5 represent progressively smaller skin areas of the distal tail. Adjacent dermatomes overlapped 15-65%. Thoracic dermatomes had a nearly vertical orientation; adjacent dermatomes overlapped by 30-75%. Dorsal roots in caudal and thoracic regions have crossed projections to the medial and lateral (but not middle) portions of the contralateral dorsal horn. These crossed projections are a possible anatomical substrate for RFs that cross the ventral or dorsal midline. The dorsal root projection patterns are consistent with those that would be predicted from the dorsal root dermatomes and dorsal horn cell somatotopy, assuming that the presynaptic terminals' somatotopy is in register with that of dorsal horn cells (the presynaptic somatotopy hypothesis; see Ref. 12).


1981 ◽  
Vol 95 (1) ◽  
pp. 93-109
Author(s):  
E. Sykova

K+ accumulates in the intercellular space as a result of neuronal activity. The changes in extracellular K+ concentration, delta[K]e (estimated by K+-selective microelectrodes), depends on neuronal activity, on the density of discharging neurones and the removal of the accumulated K+ by diffusion, active transport and current flow through cells. In the mammalian as well as the amphibian spinal cord a single volley in a peripheral nerve increases [K]e by 0.2-0.5 mmol. 1-1, while tetanic stimulation (100 Hz) by 7-8 m-mol. 1-1, with a maximum in the lower dorsal horn. Increased [K]e was also found in lumbar segments when the somatosensory cortex of the cat and medulla of the frog were stimulated. In the frog spinal cord, the tactile stimulation of the hindlimb evoked delta[K]e by about 0.1 mumol. 1-1, nociceptive stimulation by 0.2-1.0 mmol. 1-1. Spontaneous delta[K]e and dorsal root potentials (DRPs) were observed at various intervals after stimulation, associated with the decay phase of delta[K]e. It was shown that primary afferent depolarization (PAD) consists of two components: the ‘early’ component (mediated by GABA and depressed by picrotoxin or bicuculline) and the ‘late’ K+ component (potentiated by picrotoxin and bicuculline). Even when increased [K]e produces PAD, this does not mean that it also results in presynaptic inhibition. It was found that the delta[K]e produced depolarization of motoneurones and neuroglia and there is every reason to believe that this also applies to the interneurones. Evidence is available that an increase of [K]e up to 6 mmol. 1-1 facilitates impulse transmission in the spinal cord while higher levels result in its inhibition.


Neurosurgery ◽  
1984 ◽  
Vol 15 (6) ◽  
pp. 921-927
Author(s):  
Janice Ovelmen-Levitt ◽  
Betty Johnson ◽  
Purvis Bedenbaugh ◽  
Blaine S. Nashold

Abstract We performed an extracellular microelectrode analysis of the neuronal activity of cells located in deeper laminae of dorsal horns that had been deafferented by ipsilateral lumbar dorsal root rhizotomy or avulsion. Special attention was given to those cells that were recorded in preparations that were more than 6 weeks chronic. We compared the results to those obtained in nondenervated controls and in experiments in which the spinal cord was acutely transected at a midthoracic level, but had intact dorsal roots. There was an increase in ipsilateral flank and contralateral input in the chronically deafferented as compared to nondenervated controls. Differences were observed between long term rhizotomized and avulsed dorsal horns. Receptive fields extended on to flank and thoracic dermatomes after rhizotomy, often requiring only light cutaneous stimuli. Receptive fields were more restricted with avulsion injury, generally requiring moderate to strong, superficial or deep pinch. Histological analysis revealed consistent differential damage to the medial portion of Lissauer's tract with avulsion injury and subsequently more gliosis in the substantia gelatinosa. The loss of this propriospinal pathway may explain the lack of receptive field expansion on to the thoracic dermatomes and the stronger natural stimuli that were required. A higher percentage of cells with bilateral and inhibitory receptive fields was found in experiments in which the spinal cord was transected at a midthoracic level than in the controls. Ipsilateral excitatory receptive fields were also expanded as compared with control observations, but were not found on the flank. It is concluded that descending fibers have an inhibitory influence on both excitatory and inhibitory receptive fields, both ipsilaterally and contralaterally, which can be released by acute spinal cord transection. These alterations or release from inhibition may form a substrate for observations made after dorsal root denervations.


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