title: Tranexamic acid evokes pain by modulating neuronal excitability in the spinal dorsal horn.
abstract: Tranexamic acid (TXA) is an antifibrinolytic agent widely used to reduce blood loss during surgery. However, a serious adverse effect of TXA is seizure due to inhibition of γ-aminobutyric acid (GABA) and glycine receptors in cortical neurons. These receptors are also present in the spinal cord, and antagonism of these receptors in spinal dorsal horn neurons produces pain-related phenomena, such as allodynia and hyperalgesia, in experimental animals. Moreover, some patients who are injected intrathecally with TXA develop severe back pain. However, the effect of TXA on spinal dorsal horn neurons remain poorly understood. Here, we investigated the effects of TXA by using behavioral measures in rats and found that TXA produces behaviors indicative of spontaneous pain and mechanical allodynia. We then performed whole-cell patch-clamp experiments that showed that TXA inhibits GABAA and glycine receptors in spinal dorsal horn neurons. Finally, we also showed that TXA facilitates activation of the extracellular signal-regulated kinase in the spinal cord. These results indicated that TXA produces pain by inhibiting GABAA and glycine receptors in the spinal dorsal horn.
authors: Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, 951-8510 Japan.
authors: Nobuko
authors: N
authors: Ohashi
authors: Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, 951-8510 Japan.
authors: Mika
authors: M
authors: Sasaki
authors: Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, 951-8510 Japan.
authors: Masayuki
authors: M
authors: Ohashi
authors: Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, 951-8510 Japan.
authors: Yoshinori
authors: Y
authors: Kamiya
authors: Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, 951-8510 Japan.
authors: Hiroshi
authors: H
authors: Baba
authors: Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, 951-8510 Japan.
authors: Tatsuro
authors: T
authors: Kohno
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059330:GABAergic Neurons / Q000187:drug effects / Q000473:pathology; D005998:Glycine / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D053444:Inhibitory Postsynaptic Potentials; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D008954:Models, Biological; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D017208:Rats, Wistar; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D005680:gamma-Aminobutyric Acid; D014148:Tranexamic Acid; D048049:Extracellular Signal-Regulated MAP Kinases; D005998:Glycine