I am a
Home I AM A Search Login

Papers of the Week

Papers: 14 Sep 2019 - 20 Sep 2019

Animal Studies

2019 Sep/Oct




Functional Reorganization of Local Circuit Connectivity in Superficial Spinal Dorsal Horn with Neuropathic Pain States.



The spinal dorsal horn is the first relay structure coding for pain transmission and modulation. Previous anatomical and electrophysiological studies have examined spinal dorsal horn circuitry, functional studies of circuit connections and network activity. Further work is required to understand spinal cord sensory information processing that underlies pathological neuropathic pain states. Our previous studies suggest that peripheral nerve injury enhances presynaptic excitatory input onto spinal superficial dorsal horn neurons, which in turn contributes to pathologic nociception. The potential changes in local postsynaptic circuits in the dorsal horn that lead to pathologically heightened behavioral responses to pain remain largely unexplored. We combined whole cell electrophysiological recordings with laser scanning photostimulation (LSPS) to test whether the spinal nerve ligation (SNL) mouse model of neuropathic pain leads to alterations in the functional connectivity of spinal cord circuits including lamina II excitatory interneurons. Here we show that SNL enhances excitation and decreases inhibition to lamina II excitatory interneurons along with their increased glutamate-evoked excitability. The enhanced excitatory postsynaptic input and connectivity evoked by SNL eventually return to normal levels concurrently with the resolution of the neuropathic pain states. The physiological pattern highly correlates with mouse pain behaviors following SNL, supporting a neurophysiological mechanism of central sensitization and neuropathic pain that is functionally localized to the spinal dorsal horn. Together, these data support that SNL induces functional changes in synaptic input and connectivity to lamina II excitatory interneurons that code for pain perception, and thus provide new insights into the mechanism and locus of pain hypersensitivity. Neuropathic pain presumably results from alterations in neuronal circuits that process nociception. This form of pain is often maladaptive. The contribution of circuit connections and detailed local spinal cord circuits underlying neuropathic pain are not well understood. Here, we apply laser-scanning photostimulation (LSPS) combined with whole cell recordings to investigate local circuit connectivity onto the lamina II interneurons during and after recovery following spinal nerve ligation that causes pathological neuropathic pain. The present study sheds light on local circuit organization in spinal dorsal horn and shows that reciprocal changes occur in local excitatory interneurons during both peak and after the gradual normalization of neuropathic pain. This elucidates nociceptive processing changes during and after neuropathic pain conditions and suggests new treatments.