Current models of somatosensory perception emphasize transmission from primary sensory neurons to the spinal cord and on to the brain. Mental influence on perception is largely assumed to occur locally within the brain. Here we investigate whether sensory inflow through the spinal cord undergoes direct top-down control by the cortex. Although the corticospinal tract (CST) is traditionally viewed as a primary motor pathway, a subset of corticospinal neurons (CSNs) originating in the primary and secondary somatosensory cortex directly innervate the spinal dorsal horn via CST axons. Either reduction in somatosensory CSN activity or transection of the CST in mice selectively impairs behavioural responses to light touch without altering responses to noxious stimuli. Moreover, such CSN manipulation greatly attenuates tactile allodynia in a model of peripheral neuropathic pain. Tactile stimulation activates somatosensory CSNs, and their corticospinal projections facilitate light-touch-evoked activity of cholecystokinin interneurons in the deep dorsal horn. This touch-driven feed-forward spinal-cortical-spinal sensitization loop is important for the recruitment of spinal nociceptive neurons under tactile allodynia. These results reveal direct cortical modulation of normal and pathological tactile sensory processing in the spinal cord and open up opportunities for new treatments for neuropathic pain.

The changes of crystal structure and morphology in poly(glycolide), PGA, homopolymer and poly(glycolide-co-l-lactide), PGA-co-PLA, (90/10) random copolymer during in vitro degradation were investigated by gel permeation chromatography (GPC), wide-angle X-ray diffraction (WAXD), and small-angle X-ray scattering (SAXS). GPC results showed that the molecular weight and polydispersity decreased significantly during the first 2 weeks of degradation. In contrast, the mass degree of crystallinity, φ mc, determined from WAXD showed an Avrami-like behavior in both polymers, increasing rapidly within the first 2 weeks and gradually reaching a plateau value. The effect of degradation on the crystal unit cell dimensions was noticeable and anisotropic, which may reflect the process of crystal perfection in vitro. Corresponding SAXS results also showed that the long period (L), lamellar thickness (l c), and amorphous layer thickness (l a) from the crystal lamellar stacks all decreased appreciably in both PGA and PGA-co-PLA samples during the first 3 weeks of degradation. By comparing molecular weight and lamellar thickness results, we conclude that the fully degraded chain fragments have an average length of about 3 times the crystal thickness. On the basis of these results, we propose that degradation proceeds through the combined processes of chain scission and cleavage-induced crystallization in the amorphous regions via two pathways. (1) The degradation occurs in the amorphous gaps between the crystal lamellar stacks, where the amorphous chains are broken leading to greater mobility to form new crystal lamellar stacks with thinner thickness. This process significantly reduces the averaged values of L, l c , and l a. (2) The degradation process also occurs in the amorphous layer domain between the adjacent lamellae within the lamellar stacks, where chain scission causes the rapid decrease in polydispersity.

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