{
  "abstract": "Phentolamine, a non-selective α-adrenergic antagonist traditionally used for vascular conditions and local anesthetic reversal, may have properties as a modulator of pain pathways. In this study 1 using ex vivo preparations from mice, pigs, and humans, phentolamine decreased compound action potentials in a concentration-dependent manner, with a preference for C-fibers over Aδ-fibers. Notably, this effect was consistent across species, and C-fibers from NaV1.8/NaV1.9 double knockout mice exhibited reduced sensitivity to phentolamine. Patch-clamp experiments further confirmed voltage-gated sodium channel inhibition, with NaV1.8 showing the highest susceptibility. Together, these findings reveal that phentolamine’s pharmacology extends beyond adrenergic blockade, positioning it as a valuable tool for probing pain signaling pathways and a potential scaffold for the development of novel C-fiber-targeted analgesics to address chronic pain and itch disorders.",
  "authors": [
    {
      "affiliations": [
        "Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, USA"
      ],
      "name": "Ryan S D’Souza"
    },
    {
      "affiliations": [
        "Institute of Neurophysiology, University Hospital RWTH Aachen, Aachen, Germany"
      ],
      "name": "Sven Engler"
    },
    {
      "affiliations": [
        "Human Anatomy and Embryology Unit, Universitat de Barcelona Facultat de Medicina i Ciències de la Salut, Barcelona, Spain",
        "Anesthesia, HM Delfos, Barcelona, Spain"
      ],
      "name": "Hipolito Labandeyra"
    }
  ],
  "title": "Phentolamine: more than just an adrenergic blocker – a pathway to a potential analgesic?",
  "uid": "bbc39e57-cf9f-5a39-92e2-69f337c28014"
}