Role of TTX-Sensitive and TTX-Resistant Sodium Channels in Aδ- and C-Fiber Conduction and Synaptic Transmission

2008 ◽  
Vol 99 (2) ◽  
pp. 617-628 ◽  
Author(s):  
Vitor Pinto ◽  
Victor A. Derkach ◽  
Boris V. Safronov
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Dorsal Horn ◽  
Conduction Velocity ◽  
Room Temperature ◽  
Dorsal Horn Neurons ◽  
Dorsal Roots ◽  
Relative Contribution ◽  
C Fibers ◽  
C Fiber

Thin afferent axons conduct nociceptive signals from the periphery to the spinal cord. Their somata express two classes of Na+ channels, TTX-sensitive (TTX-S) and TTX-resistant (TTX-R), but their relative contribution to axonal conduction and synaptic transmission is not well understood. We studied this contribution by comparing effects of nanomolar TTX concentrations on currents associated with compound action potentials in the peripheral and central branches of Aδ- and C-fiber axons as well as on the Aδ- and C-fiber-mediated excitatory postsynaptic currents (EPSCs) in spinal dorsal horn neurons of rat. At room temperature, TTX completely blocked Aδ-fibers (IC50, 5–7 nM) in dorsal roots (central branch) and spinal, sciatic, and sural nerves (peripheral branch). The C-fiber responses were blocked by 85–89% in the peripheral branch and by 65–66% in dorsal roots (IC50, 14–33 nM) with simultaneous threefold reduction in their conduction velocity. At physiological temperature, the degree of TTX block in dorsal roots increased to 93%. The Aδ- and C-fiber-mediated EPSCs in dorsal horn neurons were also sensitive to TTX. At room temperature, 30 nM blocked completely Aδ-input and 84% of the C-fiber input, which was completely suppressed at 300 nM TTX. We conclude that in mammals, the TTX-S Na+ channels dominate conduction in all thin primary afferents. It is the only type of functional Na+ channel in Aδ-fibers. In C-fibers, the TTX-S Na+ channels determine the physiological conduction velocity and control synaptic transmission. TTX-R Na+ channels could not provide propagation of full-amplitude spikes able to trigger synaptic release in the spinal cord.

Anesthetic blockade of the dorsolateral funiculus enhances evoked activity of spinal cord dorsal horn neurons

1991 ◽  
Vol 66 (1) ◽  
pp. 140-152 ◽  
Author(s):  
L. M. Pubols ◽  
D. A. Simone ◽  
N. A. Bernau ◽  
J. D. Atkinson
Keyword(s):  
Spontaneous Activity ◽  
Dorsal Horn ◽  
Tibial Nerve ◽  
Spinal Cord Dorsal Horn ◽  
Dorsal Horn Neurons ◽  
C Fibers ◽  
C Fiber ◽  
Dorsolateral Funiculus ◽  
Electrical Stimuli ◽  
Fiber Stimulation

1. A previous study of cat lumbar dorsal horn neurons found reduced responsiveness to A-fiber stimulation 1.5-12 h after thoracic dorsolateral funiculus (DLF) lesions. The present study was undertaken to determine whether this was due to the loss of descending activity or to factors specifically associated with injury by examining the response properties of dorsal horn cells before and during lidocaine blockade of the ipsilateral DLF. Electric shocks applied to the dorsal columns were used to search for dorsal horn cells. Noxious and nonnoxious cutaneous mechanical stimuli and graded electrical stimuli applied to the tibial nerve were used to activate peripheral afferent fibers. Cells were classed as low threshold (LT), high threshold (HT), or multireceptive (MR), according to their responses to natural stimuli. Baseline data were collected from a total of 58 cells. Twelve of these were further studied after lidocaine injection of the DLF. All cells examined with lidocaine were in dorsal horn laminae III-V. 2. All cells responded to activation of tibial nerve A fibers. However, the median threshold for the HT and MR cells (200 microA) was significantly higher than that of the LT cells (75 microA). Some cells in each class were also activated by C fibers (10, 70, and 64% of the LT, HT, and MR cells, respectively). 3. For the cells that were further characterized by lidocaine blockade of the DLF, all LT cells (n = 3) responded only to A-fiber stimulation, and all HT (n = 3) and MR cells (n = 6) responded to both A- and C-fiber stimulation. 4. For LT cells, responses evoked by mechanical and electrical stimuli were unaltered by lidocaine blockade. 5. HT and MR cells showed enhanced responses to electrical stimulation of C fibers during DLF blockade. There was no consistent effect of the blockade on A-fiber-evoked responses. 6. Two of three HT and four of six MR cells studied with lidocaine had spontaneous activity, which exhibited a small but significant increase during DLF blockade. 7. Receptive fields for noxious stimulation expanded in two of six MR cells during DLF blockade. Two of three HT cells developed responses to tactile stimuli during the blockade. 8. In two additional cells (1 HT and 1 MR), spontaneous activity and responses to C-fiber input increased after the DLF was cut.(ABSTRACT TRUNCATED AT 400 WORDS)

ATP P2× Receptors and Sensory Synaptic Transmission Between Primary Afferent Fibers and Spinal Dorsal Horn Neurons in Rats

1998 ◽  
Vol 80 (6) ◽  
pp. 3356-3360 ◽  
Author(s):  
Ping Li ◽  
Amelita A. Calejesan ◽  
Min Zhuo
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Dorsal Horn ◽  
Lumbar Spinal Cord ◽  
Superficial Dorsal Horn ◽  
Primary Afferent ◽  
Dorsal Horn Neurons ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Lumbar Spinal

Li, Ping, Amelita A. Calean, and Min Zhuo. ATP P2× receptors and sensory synaptic transmission between primary afferent fibers and spinal dorsal horn neurons in rats. J. Neurophysiol. 80: 3356–3360, 1998. Glutamate is a major fast transmitter between primary afferent fibers and dorsal horn neurons in the spinal cord. Recent evidence indicates that ATP acts as another fast transmitter at the rat cervical spinal cord and is proposed to serve as a transmitter for nociception and pain. Sensory synaptic transmission between dorsal root afferent fibers and neurons in the superficial dorsal horn of the lumbar spinal cord were examined by whole cell patch-clamp recording techniques. Experiments were designed to test if ATP could serve as a transmitter at the lumbar spinal cord. Monosynaptic excitatory postsynaptic currents (EPSCs) were completely abolished after the blockade of both glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate and N-methyl-d-aspartate receptors. No residual current was detected, indicating that glutamate but not ATP is a fast transmitter at the dorsal horn of the lumbar spinal cord. Pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), a selective P2× receptor antagonist, produced an inhibitory modulatory effect on fast EPSCs and altered responses to paired-pulse stimulation, suggesting the involvement of a presynaptic mechanism. Intrathecal administration of PPADS did not produce any antinociceptive effect in two different types of behavioral nociceptive tests. The present results suggest that ATP P2×2 receptors modulate excitatory synaptic transmission in the superficial dorsal horn of the lumbar spinal cord by a presynaptic mechanism, and such a mechanism does not play an important role in behavioral responses to noxious heating. The involvement of other P2× subtype receptors, which is are less sensitive to PPADS, in acute nociceptive modulation and persistent pain remains to be investigated.

An electrophysiological study of dorsal horn neurons in the spinal cord of rats with an experimental peripheral neuropathy

1993 ◽  
Vol 69 (6) ◽  
pp. 2072-2085 ◽  
Author(s):  
J. M. Laird ◽  
G. J. Bennett
Keyword(s):  
Spinal Cord ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Dorsal Horn ◽  
Mechanical Stimulation ◽  
Injury Site ◽  
Dorsal Horn Neurons ◽  
C Fiber ◽  
The Mean ◽  
Stimulation Of

1. Extracellular single-unit recordings have been made from 295 dorsal horn neurons in the lumbar enlargement of rat spinal cord; 191 neurons in 20 rats with an experimental peripheral neuropathy, and 104 in 10 sham-operated rats. Recordings were made 9-11 days after inducing the neuropathy by tying four loose ligatures around the sciatic nerve in the nerve-injured rats or performing a sham procedure in the sham-operated rats. 2. A survey of the general properties of all neurons encountered was made in the 10 sham-operated rats (104 neurons) and compared with those seen in 17 of the nerve-injured animals (180 neurons). The vast majority (87%; 156/180) of neurons recorded in the nerve-injured animals showed abnormal characteristics; these included responses to very gentle mechanical stimulation of the nerve-injury site and to manipulations that resulted in movement of this site such as extension of the leg and probing of the skin and muscle of the thigh (53%), absence of detectable peripheral receptive fields (RFs; 56%), and very high spontaneous activity (7%). In the sham-operated rats none of the neurons recorded could be activated by gentle mechanical stimulation of the sciatic nerve, and only 6% had no detectable peripheral RF. 3. In the nerve-injured animals, 31% (55/180) of cells had both a peripheral RF, and a response to gentle mechanical stimulation of the nerve-injury site. All cells of this type tested (n = 5) showed very prolonged responses (up to 10 min long) to 15 s pinch stimuli applied to the RF and to 15 s gentle tapping of the injury site. The majority of cells in this group were excited by noxious stimuli (71%; 39/55) and had C-fiber inputs (60%; 33/55). 4. The mean threshold temperatures for evoking responses to heat stimuli in cells tested in nerve-injured rats and in sham-operated animals were not different. However, there was a group of neurons in the nerve-injured rats that had low thresholds, failed to encode stimulus intensity, and did not have a C-fiber input. 5. There were significantly fewer neurons excited by low-intensity stimulation of the skin in the nerve-injured (24%; 43/180) than in the sham-operated rats (71%; 74/104). Measurements of mechanical threshold with von Frey hairs showed that, although the mean threshold did not change, none of the cells tested in the nerve-injured animals had thresholds < 12 mN, whereas the lowest threshold recorded in the sham-operated animals was 0.2 mN.(ABSTRACT TRUNCATED AT 400 WORDS)

Tonic descending influences on receptive-field properties of nociceptive dorsal horn neurons in sacral spinal cord of rat

1990 ◽  
Vol 63 (5) ◽  
pp. 1022-1032 ◽  
Author(s):  
J. M. Laird ◽  
F. Cervero
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Intact Animal ◽  
Cervical Spinal Cord ◽  
Afferent Input ◽  
Superficial Dorsal Horn ◽  
Descending Inhibition ◽  
Dorsal Horn Neurons ◽  
C Fiber ◽  
Mechanical Thresholds

1. Single-unit electrical activity has been recorded from 34 dorsal horn neurons in the sacral segments (S1-2) of the spinal cord in halothane-anesthetized rats. All of the neurons had cutaneous receptive fields (RFs) on the rat's tail. The neurons were classified according to their responses to both innocuous and noxious mechanical stimulation of their RFs. Twenty-five cells were driven by both innocuous and noxious skin stimulation (multireceptive or class 2), and 9 neurons were driven only by noxious skin stimulation (nocireceptive or class 3). 2. The RF size, mechanical threshold, and afferent input properties of these neurons were determined in the intact anesthetized and spinalized states. Reversible spinalization was achieved by cooling the cervical spinal cord to 4 degrees C. 3. The class 2 neurons had a mean RF size of 919.8 +/- 112.0 (SE) mm2 in the intact animal. Fourteen of the 25 class 2 cells had larger RFs in the spinal state (mean increase = 330.0 mm2, SE = 79.2) and so were under tonic descending inhibition. Five neurons, all with C-fiber input, had smaller RFs (mean decrease = 247.6 mm2, SE = 136.6) and higher mechanical thresholds in the spinal state and so were under tonic descending excitation. Six neurons were unaffected by spinalization. 4. Five class 3 neurons recorded in the superficial dorsal horn had small RFs in the intact animal (mean = 201.0 mm2, SE = 48.8) and showed little or no change in RF size on spinalization (mean increase = 33.4 mm2, SE = 16.7), but their mechanical thresholds did decrease, indicating weak tonic descending inhibition. In contrast, four class 3 neurons recorded in the deep dorsal horn had larger RFs in the intact animal (mean = 566.8 mm2, SE = 156.8), and were under strong tonic descending inhibition, because they had much larger RFs (mean increase = 461.0 mm2, SE = 68.3), lower mechanical thresholds, and stronger C-fiber afferent input in the spinal state. 5. We conclude that the majority of nociceptive dorsal horn neurons are subject to a net tonic descending control of their RF properties. The class 2 neurons in the deep dorsal horn appear to be a heterogeneous population, some cells being under tonic descending excitation and others under tonic descending inhibition. Class 3 cells can be separated into those located in the superficial dorsal horn, whose RF properties show very little change on spinalization, and those in the deep dorsal horn, whose RF properties change markedly on spinalization.(ABSTRACT TRUNCATED AT 400 WORDS)

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