Antihyperalgesia by α2-GABAA Receptors Occurs Via a Genuine Spinal Action and Does Not Involve Supraspinal Sites

Drugs that enhance GABAergic inhibition alleviate inflammatory and neuropathic pain after spinal application. This antihyperalgesia occurs mainly through GABAA receptors (GABAARs) containing α2 subunits (α2-GABAARs). Previous work indicates that potentiation of these receptors in the spinal cord evokes profound antihyperalgesia also after systemic administration, but possible synergistic or antagonistic actions of supraspinal α2-GABAARs on spinal antihyperalgesia have not yet been addressed. Here we generated two lines of GABAAR-mutated mice, which either lack α2-GABAARs specifically from the spinal cord, or, which express only benzodiazepine-insensitive α2-GABAARs at this site. We analyzed the consequences of these mutations for antihyperalgesia evoked by systemic treatment with the novel non-sedative benzodiazepine site agonist HZ166 in neuropathic and inflammatory pain. Wild-type mice and both types of mutated mice had similar baseline nociceptive sensitivities and developed similar hyperalgesia. However, antihyperalgesia by systemic HZ166 was reduced in both mutated mouse lines by about 60% and was virtually indistinguishable from that of global point-mutated mice, in which all α2-GABAARs were benzodiazepine insensitive. The major (α2-dependent) component of GABAAR-mediated antihyperalgesia was therefore exclusively of spinal origin, whereas supraspinal α2-GABAARs had neither synergistic nor antagonistic effects on antihyperalgesia. Our results thus indicate that drugs that specifically target α2-GABAARs exert their antihyperalgesic effect through enhanced spinal nociceptive control. Such drugs may therefore be well-suited for the systemic treatment of different chronic pain conditions

Managing ditches for agroecological engineering of landscape. A review

International audienceAbstractAgriculture must now feed the planet with the lowest environmental impact. Landscape management is a means to protect natural resources from the adverse impacts. In particular, the adequate management of ditches could improve crop quality. Here, we review ditch design and maintenance. We found the following major points: (1) ditch networks have been primarily designed for waterlogging control and erosion prevention. Nonetheless, when properly managed, farm ditches provide other important ecosystem services, namely groundwater recharge, flood attenuation, water purification, or biodiversity conservation. (2) All ditch ecosystem services depend on many geochemical, geophysical, and biological processes, whose occurrence and intensity vary largely with ditch characteristics. (3) The major ruling characteristics are vegetative cover; ditch morphology; slope orientation; reach connections such as piped sections and weirs, soil, sediment and litter properties, biota, and biofilms; and network topology. (4) Ditch maintenance is an efficient engineering tool to optimize ecosystem services because several ditch characteristics change widely with ditch maintenance. For instance, maintenance operations, dredging, chemical weeding, and burning improve waterlogging and soil erosion control, but they are negative for biodiversity conservation. Mowing has low adverse effects on biodiversity conservation and water purification when mowing is performed at an adequate season. The effects of burning have been poorly investigated