Cytokine activin C ameliorates chronic neuropathic pain in peripheral nerve injury rodents by modulating the TRPV1 channel.

BACKGROUND AND PURPOSE: The cytokine activin C is mainly expressed in small-diameter dorsal root ganglion (DRG) neurons and suppresses inflammatory pain. However, the effects of activin C in neuropathic pain remain elusive. EXPERIMENTAL APPROACH: Male rats and wild-type and TRPV1 knockout mice with peripheral nerve injury - sciatic nerve axotomy and spinal nerve ligation in rats; chronic constriction injury (CCI) in mice - provided models of chronic neuropathic pain. Ipsilateral lumbar (L)4-5 DRGs were assayed for activin C expression. Chronic neuropathic pain animals were treated with intrathecal or locally pre-administered activin C or the vehicle. Nociceptive behaviours and pain-related markers in L4-5 DRGs and spinal cord were evaluated. TRPV1 channel modulation by activin C was measured. KEY RESULTS: Following peripheral nerve injury, expression of activin ßC subunit mRNA and activin C protein was markedly up-regulated in L4-5 DRGs of animals with axotomy, SNL or CCI. [Correction added on 26 November 2020, after first online publication: The preceding sentence has been corrected in this current version.] Intrathecal activin C dose-dependently inhibited neuropathic pain in spinal nerve ligated rats. Local pre-administration of activin C decreased neuropathic pain, macrophage infiltration into ipsilateral L4-5 DRGs and microglial reaction in L4-5 spinal cords of mice with CCI. In rat DRG neurons, activin C enhanced capsaicin-induced TRPV1 currents. Pre-treatment with activin C reduced capsaicin-evoked acute hyperalgesia and normalized capsaicin-evoked persistent hypothermia in mice. Finally, the analgesic effect of activin C was abolished in TRPV1 knockout mice with CCI. CONCLUSION AND IMPLICATIONS: Activin C inhibits neuropathic pain by modulating TRPV1 channels, revealing potential analgesic applications in chronic neuropathic pain therapy.

Supervisory control of mobile sensor networks: math formulation, simulation, and implementation.

This paper uses a novel discrete-event controller (DEC) for the coordination of cooperating heterogeneous wireless sensor networks (WSNs) containing both unattended ground sensors (UGSs) and mobile sensor robots. The DEC sequences the most suitable tasks for each agent and assigns sensor resources according to the current perception of the environment. A matrix formulation makes this DEC particularly useful for WSN, where missions change and sensor agents may be added or may fail. WSN have peculiarities that complicate their supervisory control. Therefore, this paper introduces several new tools for DEC design and operation, including methods for generating the required supervisory matrices based on mission planning, methods for modifying the matrices in the event of failed nodes, or nodes entering the network, and a novel dynamic priority assignment weighting approach for selecting the most appropriate and useful sensors for a given mission task. The resulting DEC represents a complete dynamical description of the WSN system, which allows a fast programming of deployable WSN, a computer simulation analysis, and an efficient implementation. The DEC is actually implemented on an experimental wireless-sensor-network prototyping system. Both simulation and experimental results are presented to show the effectiveness and versatility of the developed control architecture.