Corticofugal Output from the Primary Somatosensory Cortex Selectively Modulates Innocuous and Noxious Inputs in the Rat Spinothalamic System

Abstract

Sensory maps for pain can be modified by deafferentation or injury, and such plasticity has been attributed mainly to changes in the convergence of projections in "bottom-up" mechanisms. We addressed the possible contribution of "top-down" mechanisms by investigating the functional significance of corticofugal influences from the primary somatosensory cortex (S1) to the ventroposterolateral thalamic nucleus (VPL). The strong convergence of spinal and lemniscal afferents to the VPL and the close correspondence between afferents and efferents within the VPL-S1 network suggest the existence of functionally related thalamocortical circuits that are implicated in the detection of innocuous and noxious inputs. Functional characterization of single nociceptive, wide dynamic range, and non-nociceptive VPL neurons and labeling the axons and terminal fields with the juxtacellular technique showed that all three types of cells project to a restricted area, within S1. The convergence of the terminal trees of axons from VPL neurons activated by innocuous, noxious, or both inputs suggests that their inputs are not segregated into anatomically distinct regions. Microinjections within S1 were performed for pharmacological manipulation of corticofugal modulation. Glutamatergic activation of corticofugal output enhanced noxious-evoked responses and affected in a biphasic way tactile-evoked responses of VPL cells. GABA A -mediated depression of corticofugal output concomitantly depressed noxious and enhanced innocuous-evoked responses of VPL neurons. Microinjections of a GABA A antagonist on corticofugal cells enhanced noxious-evoked responses of VPL cells. Our findings demonstrate that corticofugal influences from S1 contribute to selectively modulate somatosensory submodalities at the thalamic level.

Altered somatosensory processing in trigeminal neuralgia

“…A GABAergic hypofunction of this network followed by pain hypersensitivity and delayed loss of sensory neurons was proposed as an explanation for neuropathic pain [Canavero and Bonicalzi, 1998;DaSilva et al, 2008;Woolf and Salter, 2000]. Recent studies have shown under experimental conditions in rats that a decrease of glutamatergic excitatory or alternatively an increase of GABAergic inhibitory drive from SI would reduce thalamic responsiveness to painful stimulation [Monconduit et al, 2006;Wang et al, 2007]. Thus, the observed cortical signal reduction in the present study may reflect a top-down mechanism to reduce pain related relay.…”

“…c, contralateral; i, ipsilateral. Levels of statistical significance: ***P < 0.0001, **P < 0.01, *P < 0.05. to tactile stimulation [Lamour et al, 1983;Monconduit et al, 2006]. Further, it was demonstrated that thalamocortical inputs following noxious stimulation are not clearly segregated into anatomically distinct regions in rats [Monconduit et al, 2006], and accordingly a less confined somatotopy for noxious compared to innocuous inputs has been observed in human somatosensory cortex [Apkarian et al, 2005].…”

“…One argument for the cortical origin in this study is the absence of significant differences in thalamic activations between patients and controls although admittedly thalamic activations in fMRI are small und accordingly difficult to quantify. Another argument is the fact that there are nearly ten times as many fibers projecting back from SI to the thalamus as there are in the forward direction from thalamus to cortex implying a powerful endogenous control of the processing of sensory information originating from SI [Briggs and Usrey, 2008;Monconduit et al, 2006]. This cortico-thalamic feedback network comprises both glutamatergic excitatory and GABAergic inhibitory components and is thought to gate sensory stimuli.…”

Changes of Meningeal Excitability Mediated by Corticotrigeminal Networks: A Link for the Endogenous Modulation of Migraine Pain

“…In the latter case, a five-channel Eckhorn mini-matrix microdrive system (Thomas Recordings) was used. Microelectrode signals were amplified, filtered, digitized, and discriminated with a personal computer-controlled multichannel neuronal acquisition processor (Plexon) as described previously (Monconduit et al, 2006). Baseline cortical activity and evoked trigeminovascular neuronal responses were obtained and analyzed as cumulative frequency and poststimulus histograms (PSTHs), respectively, to detect the occurrence of statistically significant neuronal responses.…”

Cortical astrocytes rewire somatosensory cortical circuits for peripheral neuropathic pain

“…Direct manipulation of the S1 cortex modulates the neuronal activity evoked by innocuous and noxious peripheral stimulation in downstream brain areas associated with pain signaling including the thalamus and anterior cingulate cortex (9,13). Such S1 cortex manipulation can temporarily relieve neuropathic pain in humans and animals (14)(15)(16).…”