Local anesthetic-like inhibition of voltage-gated Na(+) channels by the partial µ-opioid receptor agonist buprenorphine.

BACKGROUND: Opioids induce analgesia mainly by inhibiting synaptic transmission via G protein-coupled opioid receptors. In addition to analgesia, buprenorphine induces a pronounced antihyperalgesia and is an effective adjuvant to local anesthetics. These properties only partially apply to other opioids, and thus targets other than opioid receptors are likely to be employed. Here we asked if buprenorphine inhibits voltage-gated Na(+) channels. METHODS: Na(+) currents were examined by whole cell patch clamp recordings on different recombinant Na(+) channel α-subunits. The effect of buprenorphine on unmyelinated mouse C-fibers was examined with the skin-nerve preparation. Data are presented as mean ± SEM. RESULTS: Buprenorphine induced a concentration-dependent tonic (IC(50) 33 ± 2 µM) and use-dependent block of endogenous Na(+) channels in ND7/23 cells. This block was state-dependent and displayed slow on and off characteristics. The effect of buprenorphine was reduced on local anesthetic insensitive Nav1.4-mutant constructs and was more pronounced on the inactivation-deficient Nav1.4-WCW mutant. Neuronal (Nav1.3, Nav1.7, and Nav1.8), cardiac (Nav1.5), and skeletal muscle (Nav1.4) α-subunits displayed small differences in tonic block, but similar degrees of use-dependent block. According to our patch clamp data, buprenorphine blocked electrically evoked action potentials in C-fiber nerve terminals. Buprenorphine was more potent than other opioids, including morphine (IC(50) 378 ± 20 µM), fentanyl (IC(50) 95 ± 5 µM), sufentanil (IC(50) 111 ± 6 µM), remifenatil (IC(50) 612 ± 17 µM), and tramadol (IC(50) 194 ± 9 µM). CONCLUSIONS: Buprenorphine is a potent local anesthetic and blocks voltage-gated Na(+) channels via the local anesthetic binding site. This property is likely to be relevant when buprenorphine is used for pain treatment and for local anesthesia.

Protected forests in Europe approaches-harmonising the definitions for international comparison and forest policy making.

Comparison of forest protection between regions in Europe is extremely difficult, because there is such wide variation of strategies, procedures and constraints; the way forests have been used historically and their present closeness to nature also varies, and furthermore so does the definition of what constitutes a forest. For the European Ministerial Conference on the Protection of Forests in Europe (MCPFE) in 2003, forest protection has been harmonised into three categories for the sake of comparison: protection to safeguard biodiversity, protection of landscape and specific natural features, and protective forest functions. There is no single, uniform and universal model and no internationally agreed target with respect to the percentage of forests which should be protected. What is more important than a fixed percentage level of forested area (e.g. 5 or 10%) is that the protection network should be biogeographically and ecologically representative and accordingly distributed on a regional basis. Long-term practical experience and research have proved that conservation of different species of organisms can be assured by appropriate silvicultural management of multifunctional production forests. Consequently, the focus of debate in Europe appears to shift more and more from total protection in segregated areas to 'precision protection' and to combining protection and timber production in the holistic, integrated concept of modern management of forest areas.Advances in regional ecological planning and the growing adoption of naturalistic forest management practices have slowed the decline of the biological diversity in the multifunctional production forests. However, this fact is not yet widely and sufficiently acknowledged and appreciated. There is consequently a political and scientific need for continued study of the effects of naturalistic silvicultural management on the biodiversity of forests. Information from such research is crucially needed before new and additional protection networks and schemes are set up on a large-scale. Protection by voluntary contracts between parties is a workable model concept for European forestry based on private forest ownership. In small private forests, patches of forest worth protecting are often small and located within production forests. Forest certification can contribute to the efforts of maintaining biodiversity in multifunctional production forests and offers an instrument of independently monitoring and verifying that forests are managed according to the agreed criteria. Forest certification is not an alternative or a means of increasing forest protection, because as a voluntary process it cannot guarantee the permanence of protected areas or deal with issues of finance and compensation.