Nayef E. Saadé

Inhibition of nociceptive evoked activity in spinal neurons through a dorsal column-brainstem-spinal loop

In decerebrate-decerebellate cats, dorsal column stimulation (DCst), rostral to bilateral dorsal column cuts, inhibited dorsal horn neurons discharging to various types of nociceptive stimuli. Similar inhibitory effects were observed from conditioning nucleus raphe magnus stimulation. Activation of this dorsal column-brainstem-spinal loop could be part of an important supraspinal gating system to account for the alleviation of pain both by DCst and peripheral nerve stimulation in man.

Polysensory interactions on single neurons of cat inferior colliculus

In cats with upper spinal lesions disconnecting the dorsal column (DC) from the spinocervicolemniscal and ventral tract (VT) systems, single unit responses in the inferior colliculus could be evoked by DC and VT stimulation. Excitatory convergence and inhibitory interactions were observed between DC, VT, visual and auditory inputs both in the external and central subnuclei of the inferior colliculus.

Effects of 4-aminopyridine, GABA and bicuculline on cutaneous receptive fields of cat dorsal horn neurons

4-Aminopyridine (4-AP), bicuculline and GABA were applied locally to dorsal horn cells in the lumbar spinal cord in Nembutal-anaesthetized cats and in spinal cats. 4-AP expanded the cutaneous receptive field of 29 of 33 cells tested. Bicuculline and GABA had little or no effect on receptive field size.

Modulation of segmental mechanisms by activation of a dorsal column brainstem spinal loop

In decerebrate-decerebellate cats, dorsal column stimulation (DCst) rostral to selective dorsal funicular cuts, to prevent antidromic activation of afferent DC fibers, produced primary afferent depolarization and modulated reflexes at the lower spinal level. These findings indicate the importance of a DC-brainstem-spinal loop in explaining the effects of DC stimulation in man and experimental animals.

Inhibition of nociceptive withdrawal flexion reflexes through a dorsal column-brainstem-spinal loop

In decerebrate-decerebellate cats, dorsal column stimulation (DCst) rostral to dorsal funicular cuts, to prevent antidromic activation of afferent dorsal column fibers, inhibited spinal flexion reflexes evoked by nociceptive stimuli. The effects of DCst above the cuts were compared to those below the cuts. Our findings indicate that the analgesic effects of DCst can be attributed to activation of a DC-brainstem-spinal loop in addition to antidromic activation of spinal gating mechanisms.

Spinal input pathways affecting the medullary gigantocellular reticular nucleus

Abstract Single neurons were recorded in nucleus reticularis gigantocellularis of anesthetized or decerebrate cats. Most of the neurons were isolated using contralateral dorsal funicular stimulation to initially identify the neuron, and all were tested for responsiveness to, or modulation by, input from the contralateral dorsal funiculus and the ipsilateral ventrolateral tracts in the presence of either complete spinal transection sparing the dorsal funiculi or transection of the dorsal half of the spinal cord. Two-thirds of the neurons were excited by way of both spinal pathways when the stimulus was applied rostal to the spinal lesion. The remaining one-third of the neurons were excited by one pathway (90% via dorsal funiculus and 10% via ventrolateral tracts) and inhibited by the other pathway. Most neurons responded within 2 to 8 ms after stimulation of either pathway, and 4.5% were driven antidromically from the ventrolateral tracts. In cats with only the dorsal funiculi intact, all neurons tested for cutaneous responsiveness had small excitatory receptive fields; 90% responded to touch and 10% to hair bending. The thresholds to peripheral nerve stimulation suggested that these neurons were excited by way of the large Aα fibers. Nearly three-fourths of the neurons tested responded to stimulation of the medial lemniscus just caudal to the thalamus; most responded within 5 ms. In cats with only the ventral half of the spinal cord intact, nearly all neurons tested responded to electrical stimulation of each of the four paws, but only 19% responded to cutaneous stimulation (tap or noxious pinch). Clear interactions were found between the two input pathways in nearly all neurons, the pattern of effects (inhibitory and facilitatory) varying with the nature of the effects from each pathway alone. In 4% of the neurons, spontaneous discharge was found to be increased (only ventral half of spinal cord intact) or decreased (only dorsal funiculi intact) during noxious pinching of the skin. Clearly, input by way of both spinal pathways can affect most, if not all, neurons in the gigantocellular nucleus of the medullary reticular formation.

Dorsal column input to inferior raphe centralis neurons.

In anesthetized decerebellate cats with additional decerebration or decortication and with one of two types of cervical spinal lesions which either eliminated the dorsal half of the spinal cord or spared the dorsal funiculi, peripheral electric and localized natural stimuli activated neurons in the inferior raphe nuclear complex. Medial lemniscal as well as direct dorsal funicular stimulation was also effective. The majority of raphe neurons activated by stimulation of the dorsal funiculi were also discharged by ventrolateral funicular stimulation.

Cutaneous receptive field alterations induced by 4-aminopyridine

The dorsal column nuclei contain a precise somatotopic map of the body surface (ref. 8). This map is formed by the existence of small discrete receptive fields (cRFs) evoked by natural cutaneous stimuli in the cells of the nuclei. However, if percutaneous electrical stimuli are applied, there are signs of a very extensive subliminal fringe beyond the cRF since responses, often apparently monosynaptic, are evoked by stimuli distant from the cRFL This subliminal fringe might provide a basis for the observed plasticity of connections to dorsal column nuclei la. It has been shown that cold block of the normal input to the gracile nucleus results in the immediate appearance of novel RFs in some cells 8. If dorsal roots supplying the gracile nucleus are cut, there is a slow appearance of new inputs to cells which have lost their normal afferent drive 9 in addition to the immediate change 3. It is therefore of interest to find if the application of excitatory chemicals would reveal the existence of ineffective inputs. In this study, the convulsant 4-aminopyridine (4-AP) has been applied to test for the existence of dormant inputs. Its mode of action seems to be presynaptic, synaptic and postsynapticS,6,11,1L The complexity of this action does not concern us here since the intention was only to raise the level of excitability to reveal normally ineffective inputs. The action is non-specific, facilitating both inhibitory as well as excitatory connections 5,6. Systemic 4-AP has been shown to unmask dormant connections in visual cortex 4. Adult cats were anaesthetized with Nembutal (30 mg/kg, i.p.) with additional doses administered as needed i.v. during the experiment. They were paralyzed with Flaxedil and CO2, temperature and blood pressure were monitored. Holes were drilled in the parietal bone to place stimulating electrodes stereotactically in the 2 medial lemnisci (co-ordinates A5, L4.5, V1.8). The dorsal column nuclei were exposed by removing the atlanto-occipital membrane and a portion of the occipital bone. Extra-

Interactions of inputs from dorsal columns and ventral tracts with visual inputs on single neurons of cat superior colliculus

Abstract In cats with upper spinal lesions disconnecting the dorsal column (DC) from the spinocervicolemniscal and ventral tract (VT) systems, single unit responses in the superior colliculus could be evoked by DC and VT stimulation. Excitatory convergence, as well as facilitatory and inhibitory interactions, were observed between DC, VT, visual and auditory inputs.

Interactions of ventral tract and dorsal column inputs into the cat cuneate nucleus

In decerebrate- decerebellate cats with spinal lesions separating the dorsal column (DC) from the spinocervicothalamic and ventral tract (VT) pathways, conditioning VT stimulation activated a few, but inhibited most, of the cuneate neurons discharging to test DC stimulation. This VT input into the cuneate nucleus is mediated through the brain stem.