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.

Morphology and Synaptic Pattern of Calretinin-immunoreactive Neurons in the Superficial Dorsal Horn of the Rat Spinal Cord / 대한해부학회지

The distribution and the synaptic relationships of calretinin-immunoreactive neurons were studied in the superficial dorsal horn of the rat spinal cord. Calretinin-immunoreactive neurons and fibers were found in all laminae of spinal cord. The densest staining of both cell bodies and fibers occurred in the superficial laminae. In lamina I, marginal cells and other neurons with small round cell bodies showed calretinin-like immunoreactivity. A calretinin-immunoreactive plexus of nerve fibers was also found in this lamina. Lamina II was densely packed with calretinin-immunoreactive neuronal elements. The outer layer of lamina II was primarily composed of calretinin-immunoreactive neurons with a round or oval shape, whereas in the inner layer dorsoventrally orientated labeled neurons with spindle-shaped cell bodies were observed. Densely labeled neuropils with punctate profiles were also seen. By electron microscopy most of the labeled punctate profiles appeared to be dendrites, but axonal profiles were also found in smaller numbers. Labeled dendritic profiles established symmetric or asymmetric synapses with unlabeled axons and labeled axons established primarily symmetric synaptic contacts with unlabeled dendrites. Synaptic contacts between two calretinin-immunoreactive processes were observed infrequently.