Interaction between neurons in different laminae of the dorsal horn of the spinal cord. A correlation study in normal and neuropathic rats.
ABSTRACT Simultaneous recordings of 135 pairs of units, located respectively in the superficial (I-IIo) and deep (V) laminae of the dorsal horn of the lumbar spinal cord of anaesthetized and paralysed animals, were performed both from normal (62 pairs) and from peripherally injured (chronically constricted sciatic nerve) rats (73 pairs). In each pair, one neuron was classified as nociceptive, responding only to noxious stimuli, and the other as a wide dynamic range neuron, responding to both non-noxious and noxious stimuli. To understand if some interaction was present between diverse neurons modulated by noxious inputs, we used cross-correlation techniques. The responses of simultaneously recorded pairs of units to suprathreshold (5 mA, 0.5 ms) electrical stimuli were used. A clearly delayed peak in the cross-correlograms of recordings from normal animals was present, indicating connectivity of superficial and deep-layer cells. This feature was not present in the cross-correlograms obtained from nerve-injured animals. Even if a specific pathway cannot be explicitly assigned to support these functional results, an overall connection between superficial and deep layers of the spinal cord is suggested. These connections are supposed to be either inactive or rearranged in the nerve-injured rats, thus suppressing a well timed coordinated connectivity. This anomaly could underlie a reduced degree of functional coherence in the modulation of nociceptive spinal inputs in cases of chronic pain.
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ABSTRACT: 1. The effects of repetitive stimulation of primary afferents in lumbar dorsal roots on synaptic transmission in the dorsal horn (DH) were studied in a rat spinal cord slice-dorsal root ganglion (DRG)-peripheral nerve trunk preparation by the use of intracellular recording from neurons (n = 115) of the spinal dorsal horn (depth 147 +/- 139, mean +/- SD). All DH neurons were excited synaptically by electrical stimulation of the dorsal root or the peripheral nerve trunk. The electrical shocks were calibrated to produce activation either of large fibers (10-20 V, 0.02 ms) or the whole fiber population including unmyelinated afferents (supramaximal stimulus: > 35 V, 0.5 ms). Postsynaptic potentials induced by low intensity repetitive stimulation of primary afferents at frequencies below 5 Hz failed to produce a prolonged change in the resting membrane potential. In 97/115 DH neurons, slow excitatory postsynaptic potentials (EPSP)--evoked by high intensity low-frequency repetitive stimulation (0.1-2 Hz) of primary afferents--summated, producing a prolonged cumulative depolarization. In the remaining 18/115 DH neurons, high intensity low-frequency stimulation produced a cumulative hyperpolarizing response. 2. In 22 of 97 neurons that responded to high intensity repetitive stimulation with a cumulative depolarization, wind-up in the firing of action potentials was recorded. In all but two experiments, neurons that responded with wind-up to stimulation of one root responded with wind-up to stimulation of the adjacent dorsal root. In 14/22 wind-up neurons, the synaptic response to high intensity stimulation of primary afferents was composed of a short latency EPSP, followed by an inhibitory postsynaptic potential (IPSP), followed by a slow EPSP. The decrease of the amplitude and duration of the IPSP obtained during train stimulation did not seem to contribute to facilitation of transmission induced by repetitive stimulation. 3. The wind-up in firing of action potentials was followed by a prolonged potentiation of synaptic transmission in tetanized synapses. A test of other, adjacent primary afferents revealed that these synapses in the neurons in the superficial laminae had not undergone potentiation. This "synaptic specificity" of post-wind-up potentiation suggested that the mechanism for the induction of stimulation-dependent changes in the excitability of the DH neuron is presynaptic to the recorded-from neuron. 4. In a concentration of 0.5 microM and higher, tetrodotoxin (TTX) applied to sensory neurons selectively blocked action potentials in large myelinated primary afferents.(ABSTRACT TRUNCATED AT 400 WORDS)Journal of Neurophysiology 01/1994; 71(1):216-28. · 3.30 Impact Factor
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ABSTRACT: Recently, Bennett and Xie reported that when the sciatic nerve of the rat is ligated loosely, the rat develops a pain syndrome with many features similar to those observed in neuropathic pain states in man. Anatomical and physiological studies to date indicate that the major pathology is a loss of large diameter myelinated fibers distal to the ligatures, with more subtle changes in small myelinated fibers. With a view to evaluating possible changes in the unmyelinated fibers, we have performed an electron microscopic analysis of the sciatic nerve 2 weeks after four ligatures were applied, at which time the animals displayed profound hyperalgesia and mechanical and thermal allodynia. Cross-sectional photomontages of regions proximal and distal to the ligatures were studied. Consistent with light microscopic and electrophysiological studies, we found a near complete loss of large myelinated fibers distal to the ligatures. Phagocytosis of large fibers was common. There was also considerable variation in the damage to small myelinated fibers. In some fascicles many small (less than 3 microns) myelinated axons remained; in other fascicles none could be detected. Importantly, we also found significant changes in the unmyelinated fiber spectrum. Counts of unmyelinated axons revealed a 34% and 71% decrease in the distal compared to the proximal nerve, in the two rats studied. The large clusters of unmyelinated axons that characterize normal nerve (and the nerve proximal to the ligatures) were rarely found distally. Rather, many of the unmyelinated axons coursed singly or in very loose bundles. Many of the surviving axons were shrunken and distorted, although still in contact with Schwann cells.(ABSTRACT TRUNCATED AT 250 WORDS)Pain 01/1992; 47(3):359-67. · 5.64 Impact Factor
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ABSTRACT: Morphology or peripheral myelinated fibres was analyzed in rats exhibiting hyperalgesia and allodynia with mechanical and thermal stimuli, consecutive to a mononeuropathy induced by 4 loose ligatures around a sciatic nerve. This preliminary study was based on weeks 2-3 after surgery, the time of the maximum alterations of the pain-related behaviour. At this time, contrasting with a marked decrease of the large afferent fibres a consistent number of much less than 5 micron fibres was pointed out. In addition to their extremely short internodal length, the majority of these fibres had an abnormal g-ratio, thus an abnormal myelin sheath. It is suggested that this group of abnormal fibres might be related to the A delta fibres described in neuromas and involved in pain-related behaviours seen in the mononeuropathic rats.Neuroscience Letters 04/1990; 111(1-2):28-33. · 2.03 Impact Factor