WE examined whether endothelin-1 (ET-1), a potent vasoconstrictive peptide secreted in high concentration by metastatic prostate cancer cells, produces endothelin receptor-dependent pain behavior when applied to rat sciatic nerve. ET-1 (200–800 μM) applied to the epineurial surface of rat sciatic nerve produced reliable, robust, unilateral hindpaw flinching lasting 60 min. Preemptive systemic morphine completely blocked this effect in a naloxone-reversible manner, suggesting that this behavior was pain-related. Equipotent doses of epineurially applied epinephrine had no effect, suggesting that ET-1 effects are on tissue sites other than sciatic nerve microvessels. Prior and co-administration of BQ-123, an endothelin-A (ETA) receptor antagonist, also blocked ET-1-induced hindpaw flinching establishing that pain behavior induced by ET-1 application to rat sciatic nerve is ETA receptor mediated.

Background: Epidural corticosteroid injections are used frequently worldwide in the treatment of radicular pain. Concerns have arisen involving rare major neurologic injuries after this treatment. Recommendations to prevent these complications have been published, but local implementation is not always feasible due to local circumstances, necessitating local recommendations based on literature review.Methods: A work group of 4 stakeholder pain societies in Belgium, The Netherlands, and Luxembourg (Benelux) has reviewed the literature involving neurological complications after epidural corticosteroid injections and possible safety measures to prevent these major neurologic injuries.Results: Twenty‐six considerations and recommendations were selected by the work group. These involve the use of imaging, injection equipment particulate and nonparticulate corticosteroids, epidural approach, and maximal volume to be injected.Conclusion: Raising awareness about possible neurological complications and adoption of safety measures recommended by the work group aim at reducing the risks for these devastating events.