Spinal PKCα inhibition and gene-silencing for pain relief: AMPAR trafficking at the synapses between primary afferents and sensory interneurons

Upregulation of Ca2+-permeable AMPA receptors (CP-AMPARs) in dorsal horn (DH) neurons has been causally linked to persistent inflammatory pain. This upregulation, demonstrated for both synaptic and extrasynaptic AMPARs, depends on the protein kinase C alpha (PKCα) activation; hence, spinal PKC inhibition has alleviated peripheral nociceptive hypersensitivity. However, whether targeting the spinal PKCα would alleviate both pain development and maintenance has not been explored yet (essential to pharmacological translation). Similarly, if it could balance the upregulated postsynaptic CP-AMPARs also remains unknown. Here, we utilized pharmacological and genetic inhibition of spinal PKCα in various schemes of pain treatment in an animal model of long-lasting peripheral inflammation. Pharmacological inhibition (pre- or post-treatment) reduced the peripheral nociceptive hypersensitivity and accompanying locomotive deficit and anxiety in rats with induced inflammation. These effects were dose-dependent and observed for both pain development and maintenance. Gene-therapy (knockdown of PKCα) was also found to relieve inflammatory pain when applied as pre- or post-treatment. Moreover, the revealed therapeutic effects were accompanied with the declined upregulation of CP-AMPARs at the DH synapses between primary afferents and sensory interneurons. Our results provide a new focus on the mechanism-based pain treatment through interference with molecular mechanisms of AMPAR trafficking in central pain pathways

Powered knee orthosis for performance of assistance and rehabilitation purposes

Such modern social issues as demographic ageing and relevance of living conditions enhancement, along with mobility maintenance of different population groups, makes powered orthosis and exoskeleton the core research and application issue. Being widely used, they play a key role for medication purposes, such as rehabilitation of patients suffering from stroke, spinal cord injuries or lower limb surgeries. From the perspective of a healthy person, powered orthosis and exoskeleton can help increasing the body performance capabilities, allowing transferring a heavy weight, moving faster and further. In the long term, such devices can find an application in sport, tourism and industry. This article describes a pilot version of a powered knee orthosis based on series elastic actuator (SEA) with flexible hydraulic transmission