Membrane Properties of Physiologically Classified Rat Dorsal Horn Neurons In Vitro: Correlation with Cutaneous Sensory Afferent Input (original) (raw)
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Superficial dorsal horn neurons with double spike activity in the rat
Neuroscience Letters, 2007
Superficial dorsal horn neurons promote the transfer of nociceptive information from the periphery to supraspinal structures. The membrane and discharge properties of spinal cord neurons can alter the reliability of peripheral signals. In this paper, we analyze the location and response properties of a particular class of dorsal horn neurons that exhibits double spike discharge with a very short interspike interval (2.01 ± 0.11 ms). These neurons receive nociceptive C-fiber input and are located in laminae I-II. Double spikes are generated spontaneously or by depolarizing current injection (interval of 2.37 ± 0.22). Cells presenting double spike (interval 2.28 ± 0.11) increased the firing rate by electrical noxious stimulation, as well as, in the first minutes after carrageenan injection into their receptive field. Carrageenan is a polysaccharide soluble in water and it is used for producing an experimental model of semi-chronic pain. In the present study carrageenan also produces an increase in the interval between double spikes and then, reduced their occurrence after 5-10 min. The results suggest that double spikes are due to intrinsic membrane properties and that their frequency is related to C-fiber nociceptive activity. The present work shows evidence that double spikes in superficial spinal cord neurones are related to the nociceptive stimulation, and they are possibly part of an acute pain-control mechanism.
The Journal of physiology, 1993
1. The cutaneous mechanoreceptive fields (RFs) of forty-two lumbar dorsal horn neurones have been examined intracellularly using the hemisected spinal cord-hindlimb preparation of 10 to 14-day-old rats. The neurones were classified into three groups on the basis of their excitatory responses to innocuous and noxious mechanical stimulation; the majority (25/42) were activated by noxious and innocuous stimuli and were classed as 'wide-dynamic' type (WDR). 'Nociceptive-specific' neurones (NS) which were excited by noxious stimuli made up the next largest group (12/42) followed by 'low-threshold' neurones (LT, 5/42) which responded only weakly to noxious stimuli. Another fourteen neurones which did not respond to peripheral stimuli were used to test antagonist selectivity against excitatory amino acid agonists. 2. The response to light touch or pinch consisted of an initial EPSP and cell firing followed by subthreshold EPSPs. The mean +/- S.E.M. values for the am...
Differential Modulation of Dorsal Horn Neurons by Various Spinal Cord Stimulation Strategies
Biomedicines, 2021
New strategies for spinal cord stimulation (SCS) for chronic pain have emerged in recent years, which may work better via different analgesic mechanisms than traditional low-frequency (e.g., 50 Hz) paresthesia-based SCS. To determine if 10 kHz and burst SCS waveforms might have a similar mechanistic basis, we examined whether these SCS strategies at intensities ostensibly below sensory thresholds would modulate spinal dorsal horn (DH) neuronal function in a neuron type-dependent manner. By using an in vivo electrophysiological approach in rodents, we found that low-intensity 10 kHz SCS, but not burst SCS, selectively activates inhibitory interneurons in the spinal DH. This study suggests that low-intensity 10 kHz SCS may inhibit pain-sensory processing in the spinal DH by activating inhibitory interneurons without activating DC fibers, resulting in paresthesia-free pain relief, whereas burst SCS likely operates via other mechanisms.
The Journal of Physiology
1. Single-unit extracellular recordings were made from thirty-one dorsal horn neurones in the sacral spinal cord of barbiturate-anaesthetized rats. Each neurone was tested with four noxious mechanical pinches applied to its receptive field on the tail. Each pinch lasted 120 s, with a step-like change in intensity after 60 s. In two pinches the step increased the intensity, from 4 to 6 N or from 6 to 8 N, and in two the step decreased the intensity, from 8 to 6 N or from 6 to 4 N.
Journal of Neuroscience, 2010
Rationally, an increased intrinsic excitability of dorsal horn neurons could be a factor contributing to alter the gain of the nociceptive system during central sensitization, however direct evidence is scarce. Here we have examined this hypothesis using current and voltageclamp recordings from dorsal horn neurons in the spinal cord in vitro preparation obtained from mice pups of either sex. Cords were extracted from carrageenan-pretreated and control animals to allow for comparison.
Pain, 1994
Nociceptive primary afferents have the capacity to induce a state of increased excitability or central sensitization in dorsal horn neurones. This contributes to the mechanical hypersensitivity (allodynia) which occurs after peripheral tissue injury where low-mechanothreshold primary afferent activation begins to elicit pain. The relative susceptibility of dorsal horn cells with an apparent exclusive nociceptive input (nociceptive-specific (NS) or high-threshold (HT) cells) and those with a convergent input from low-and high-threshold mechanoreceptors (wide-dynamic-range (WDR) or multireceptive neurones) to sensitivity changes has been disputed. We have examined whether high-mechanothreshold neurones in the superficial dorsal and the ventral horn can modify their sensitivity following cutaneous application of the chemical irritant mustard oil. This produced both a prolonged reduction in the mechanical threshold of the cutaneous flexion withdrawal reflex, recorded from semitendinosus a-motor neurones, and an increase in the activity evoked in these neurones by low-intensity touch stimuli to the glabrous skin. Eight NS or HT only cells, defined in terms of their cutaneous mechanoreceptive field properties, were recorded in the superficial dorsal horn before and after cutaneous application of mustard oil. Mustard oil was applied outside of the mechanical receptive field of the cells and produced a transient increase in action potential discharge in 4 cells but increased the mechanoreceptive field size in all cells for 30-60 min. Mechanical thresholds declined in 6 cells to levels associated with low-threshold (LT) and WDR cells, and this was accompanied by recruitment of a novel brush/ touch response in 5 cells. The responses evoked by graded electrical stimulation of the sural nerve were tested in 5 cells. Only 1 cell failed to show any change after mustard oil. In 3 cells, an increase in the response to A-fibre afferents occurred, a novel A-fibre response was recruited in 2 cells and the C-fibre response increased in 2 cells. Cells in the superficial dorsal horn of the rat spinal cord that are normally NS can begin, therefore, to respond to LT primary afferent mechanoreceptors after an increase in central excitability produced by activation of peripheral chemoreceptors.
Neuroscience, 1993
Intracellular recordings from neurons in the dorsal root ganglion and dorsal horn, in an in vitro spinal cord-dorsal root ganglion preparation, were used to investigate the role of large and small afferent fibers in the sensory synaptic transmission of the superficial dorsal horn. Raising the extracellular potassium concentration from 3.1 to 25-50 mM in the dorsal root ganglion compartment evoked a large amplitude depolarization and blocked action potentials in the large neurons of the dorsal root ganglion, and it s~apti~lly excited dorsal horn neurons. Excitatory postsynaptic potentials that were evoked by electrical stim~ation of large myelinated fibers, but not those evoked by activation of small unmyelinated fibers, were blocked by the potassium treatment of the dorsal root. Tetrodotoxin (0.3-IOpM), when applied to the sensory neurons, abolished action potentials in large myelinated fibers but had no effect on the potassium-induced depolarization of the soma of large neurons of the dorsal root ganglion. Bath application of tetrodotoxin to the dorsal root ganglion blocked the postsynaptic potentials evoked in dorsal horn neurons by electrical stimulation of large fibers (stimulus intensity lO-2OV, 0.02 ms) but failed to block postsynaptic potentials induced by electrical stimulation of slow fibers (stimulus intensity > 3.5 V, 0.5 ms). In addition, the tetrodotoxin failed to block the synaptic activation of dorsal horn neurons which was induced by the application of high potassium to sensory neurons. Cap&tin (IO-LOOhM, lOs), applied to the sensory neurons, resulted in a prolonged synaptic activation of the dorsal horn neurons and a subsequent long lasting desensitization. During the period of capsaicin d~nsiti~tion, synaptic activation of dorsal horn neurons by application of high potassium to the dorsal root ganglion and electrical stimulation of slow fibres was blocked. The opioid receptor agonist (D-Ala2, D-Leu5)-enkephalinamide (1 PM), applied to the spinal cord slice, abolished the dorsal horn neuron excitation evoked by electrical or chemical activation of slow primary afferent fibers. These findings indicate that high concentrations of K+ applied to the dorsal root ganglia selectively activate a primary afferent input to the dorsal horn, which is capsaicin sensitive and tetrodotoxin resistant.
Brain Research, 1993
The nociceptive nature of the neurons of the superficial dorsal horn (laminae I-liD which project to the medullary ventrolateral reticular formation is studied in the rat. Medullary injections of Fluoro-Gold showed exclusive retrograde labeling of laminae I-III cells when the tracer filled a zone intermediate between the lateral tip of the lateral reticular nucleus and the spinal trigeminal nucleus, pars caudalis. This zone is here called VLMIat. Following noxious mechanical or thermal stimulation of the skin, double-labeled neurons, which stained retrogradely and were Fos-immunoreactive, prevailed in laminae I and Iio. Double-labeled neurons were few in lamina IIi after thermal stimulation and entirely lacking in lamina III after the two kinds of stimulation. Findings in lamina I confirm previous electrophysiological data (see Men6trey et al., J. Neurophysiol., 52 (1984) 595-611) showing that lamina I cells projecting to the ventrolateral reticular medulla convey noxious messages. The occurrence of numerous double-labeled cells in lamina IIo suggests that this lamina is also involved in nociceptive transmission to the VLMIat.
Characterization of cutaneous and articular sensory neurons
Background: A wide range of stimuli can activate sensory neurons and neurons innervating specific tissues often have distinct properties. Here, we used retrograde tracing to identify sensory neurons innervating the hind paw skin (cutaneous) and ankle/knee joints (articular), and combined immunohistochemistry and electrophysiology analysis to determine the neurochemical phenotype of cutaneous and articular neurons, as well as their electrical and chemical excitability. Results: Immunohistochemistry analysis using RetroBeads as a retrograde tracer confirmed previous data that cutaneous and articular neurons are a mixture of myelinated and unmyelinated neurons, and the majority of both populations are peptidergic. In whole-cell patch-clamp recordings from cultured dorsal root ganglion neurons, voltage-gated inward currents and action potential parameters were largely similar between articular and cutaneous neurons, although cutaneous neuron action potentials had a longer half-peak duration (HPD). An assessment of chemical sensitivity showed that all neurons responded to a pH 5.0 solution, but that acid-sensing ion channel (ASIC) currents, determined by inhibition with the nonselective acid-sensing ion channel antagonist benzamil, were of a greater magnitude in cutaneous compared to articular neurons. Forty to fifty percent of cutaneous and articular neurons responded to capsaicin, cinnamaldehyde, and menthol, indicating similar expression levels of transient receptor potential vanilloid 1 (TRPV1), transient receptor potential ankyrin 1 (TRPA1), and transient receptor potential melastatin 8 (TRPM8), respectively. By contrast, significantly more articular neurons responded to ATP than cutaneous neurons. Conclusion: This work makes a detailed characterization of cutaneous and articular sensory neurons and highlights the importance of making recordings from identified neuronal populations: sensory neurons innervating different tissues have subtly different properties, possibly reflecting different functions.
Brief and prolonged effects of Lissauer tract stimulation on dorsal horn cells
Pain, 1999
Increased excitability of dorsal horn neurones may play a critical role in producing some pain states and there is evidence that the excitability of neurones lying throughout the dorsal horn is subject to regulation by cells in its most super®cial laminae. This paper examines the effect on dorsal horn cell receptive ®elds and excitability of the speci®c activation of Lissauer's tract, a tract containing propriospinal axons which arise from cells in the substantia gelatinosa and which project to the substantia of neighbouring spinal segments. Experiments were carried out on anaesthetised spinal rats in the L3-4 spinal segments with microelectrode stimulation on the surface of the Lissauer tract (LT) and microelectrode recording of single cells or small groups of cells that responded to gentle brushing on the skin. Single shocks or brief trains of low-level stimuli to the LT produced a characteristic long-latency dorsal root potential (DRP) on the L3 dorsal root and a brief burst of ®ring in super®cial cells with no stimulation of primary afferents. Generally, this was accompanied by no excitation of deeper dorsal horn cells but commonly by a period of inhibition, often followed by facilitation. We then turned to the effect of long periods (30±90 min) of continual LT stimulation because we had seen hints of prolonged facilitation of the deeper cells after periods of such stimulation. Trains of 5 stimuli separated by 2 ms and repeated every 200 ms were used with individual pulses of 200 ms duration and less than 10 mA amplitude. This resulted in a shift of the effect on deep cells from primarily inhibition to mainly facilitation. We then examined in detail the effect of these long periods of LT stimulation on the size of receptive ®elds (RFs) of dorsal horn cells ®rst on single units and then by repeated mapping of the RFs of small groups of cells. Control periods of 60 min with no LT stimulation produced no signi®cant RF changes but 30, 60 or 90 min of LT stimulation produced successively greater expansions of RFs. When the LT stimulus was turned off after 1 h, the RFs remained expanded for at least 2 h. The spike height of these cells remained unchanged. The effect was not in¯uenced by the NMDA antagonist MK801 but was imitated by the GABA A antagonist picrotoxin. It is concluded that the prolonged expansion of RFs could not be produced by modulation of descending control since the animals had spinal transections. Neither was it dependent on an NMDA-sensitive mechanism. With these data it is not possible to conclude whether the mechanism is pre-synaptic, post-synaptic or both. It is proposed that the most likely explanation is a decrease in the normal tonic inhibition operated in part by a GABA dependent mechanism. This phenomenon may play a role in prolonged pathological states of increased spinal cord excitability. q 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.