Lamina specific loss of inhibition may lead to distinct neuropathic manifestations: a computational modeling approach

Introduction It has been reported that inhibitory control at the superficial dorsal horn (SDH) can act in a regionally distinct manner, which suggests that regionally specific subpopulations of SDH inhibitory neurons may prevent one specific neuropathic condition. Methods In an attempt to address this issue, we provide an alternative approach by integrating neuroanatomical information provided by different studies to construct a network-model of the SDH. We use Neuroids to simulate each neuron included in that model by adapting available experimental evidence. Results Simulations suggest that the maintenance of the proper level of pain sensitivity may be attributed to lamina II inhibitory neurons and, therefore, hyperalgesia may be elicited by suppression of the inhibitory tone at that lamina. In contrast, lamina III inhibitory neurons are more likely to be responsible for keeping the nociceptive pathway from the mechanoreceptive pathway, so loss of inhibitory control in that region may result in allodynia. The SDH network-model is also able to replicate non-linearities associated to pain processing, such as Aβ-fiber mediated analgesia and frequency-dependent increase of the neural response. Discussion By incorporating biophysical accuracy and newer experimental evidence, the SDH network-model may become a valuable tool for assessing the contribution of specific SDH connectivity patterns to noxious transmission in both physiological and pathological conditions.

The implementation of the Neuroid in the Gate Control System leads to new ideas about pain processing

INTRODUCTION: Several theories have been proposed to elucidate the mechanisms related with pain perception, among which, the Gate Control Theory (GCT) provides one of the most explicit explanations. This theory, as elegantly conceived, is unable to explain how the Frequency-Intensity (F-I) curves exhibited by Aβ- and C-fibres influence pain processing. In this paper, a novel neuron-model known as the Neuroid, which emphasizes the functional rather the physiological character of nerve cells, was used as the main building block to replicate the Gate Control System (GCS). METHODS: Two Aβ-fibre models were built: one model that preserved the paradoxical relation between the activation threshold and the F-I curve slope, and one model based on the hypothetical average response across the receptive field. RESULTS: The results suggest that the average response of the Aβ-fibres does not increase monotonically but reaches a plateau for high intensity stimuli. In addition, it was seen that activation of C-fibres does not necessarily imply the activation of projection neurons and, therefore, the onset of pain sensation. Also, we observed that the activation of Aβ-fibres may both, decrease and increase the activity of the projections neurons, an aspect which has not been directly described in previous works. CONCLUSION: Hypothetical implications arise as a consequence of the implementation of the Neuroid, specifically, about the correlation between the intensity of stimulation and the physiological pain threshold.