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Tranexamic acid evokes pain by modulating neuronal excitability in the spinal dorsal horn.

Ohashi N, Sasaki M, Ohashi M, Kamiya Y, Baba H, Kohno T - Sci Rep (2015)

Bottom Line: Tranexamic acid (TXA) is an antifibrinolytic agent widely used to reduce blood loss during surgery.However, the effect of TXA on spinal dorsal horn neurons remain poorly understood.These results indicated that TXA produces pain by inhibiting GABAA and glycine receptors in the spinal dorsal horn.

View Article: PubMed Central - PubMed

Affiliation: Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, 951-8510 Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Assessment of behavioral response to intrathecal and intraperitoneal injection of tranexamic acid (TXA).(A) Total time devoted to licking/biting responses during a 60-min observation period is increased in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. (B) The latency to the start of the behavior is shortened in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. (C) Mechanical thresholds for paw withdrawal in response to von Frey stimulation are significantly reduced in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. Concentrations of intrathecal or intraperitoneal injected TXA range from 0.001 to 0.1 pmol and from 10 to 100 μmol, respectively. The data are given as mean ± SD. In each dose group, n = 5; *P < 0.05, **P < 0.01 by one or two-way ANOVA.
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f1: Assessment of behavioral response to intrathecal and intraperitoneal injection of tranexamic acid (TXA).(A) Total time devoted to licking/biting responses during a 60-min observation period is increased in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. (B) The latency to the start of the behavior is shortened in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. (C) Mechanical thresholds for paw withdrawal in response to von Frey stimulation are significantly reduced in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. Concentrations of intrathecal or intraperitoneal injected TXA range from 0.001 to 0.1 pmol and from 10 to 100 μmol, respectively. The data are given as mean ± SD. In each dose group, n = 5; *P < 0.05, **P < 0.01 by one or two-way ANOVA.

Mentions: To examine whether TXA evokes pain responses, we investigated the actions of TXA using behavioral measures, such as licking/biting, in rats. Total time devoted to licking/biting behaviors during the 60-min period following intrathecal or intraperitoneal injection of TXA increased in a concentration-dependent manner at doses from 0.001 to 0.1 pmol or from 10 to 100 μmol, respectively (each dose group: n = 5, P < 0.05 by one-way ANOVA, Fig. 1A). Similarly, the latency between TXA injection and the onset of licking/biting behaviors shortened in a concentration-dependent manner (each dose group: n = 5, P < 0.05 by one-way ANOVA, Fig. 1B).


Tranexamic acid evokes pain by modulating neuronal excitability in the spinal dorsal horn.

Ohashi N, Sasaki M, Ohashi M, Kamiya Y, Baba H, Kohno T - Sci Rep (2015)

Assessment of behavioral response to intrathecal and intraperitoneal injection of tranexamic acid (TXA).(A) Total time devoted to licking/biting responses during a 60-min observation period is increased in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. (B) The latency to the start of the behavior is shortened in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. (C) Mechanical thresholds for paw withdrawal in response to von Frey stimulation are significantly reduced in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. Concentrations of intrathecal or intraperitoneal injected TXA range from 0.001 to 0.1 pmol and from 10 to 100 μmol, respectively. The data are given as mean ± SD. In each dose group, n = 5; *P < 0.05, **P < 0.01 by one or two-way ANOVA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4544020&req=5

f1: Assessment of behavioral response to intrathecal and intraperitoneal injection of tranexamic acid (TXA).(A) Total time devoted to licking/biting responses during a 60-min observation period is increased in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. (B) The latency to the start of the behavior is shortened in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. (C) Mechanical thresholds for paw withdrawal in response to von Frey stimulation are significantly reduced in a concentration-dependent manner by intrathecal or intraperitoneal injection of TXA. Concentrations of intrathecal or intraperitoneal injected TXA range from 0.001 to 0.1 pmol and from 10 to 100 μmol, respectively. The data are given as mean ± SD. In each dose group, n = 5; *P < 0.05, **P < 0.01 by one or two-way ANOVA.
Mentions: To examine whether TXA evokes pain responses, we investigated the actions of TXA using behavioral measures, such as licking/biting, in rats. Total time devoted to licking/biting behaviors during the 60-min period following intrathecal or intraperitoneal injection of TXA increased in a concentration-dependent manner at doses from 0.001 to 0.1 pmol or from 10 to 100 μmol, respectively (each dose group: n = 5, P < 0.05 by one-way ANOVA, Fig. 1A). Similarly, the latency between TXA injection and the onset of licking/biting behaviors shortened in a concentration-dependent manner (each dose group: n = 5, P < 0.05 by one-way ANOVA, Fig. 1B).

Bottom Line: Tranexamic acid (TXA) is an antifibrinolytic agent widely used to reduce blood loss during surgery.However, the effect of TXA on spinal dorsal horn neurons remain poorly understood.These results indicated that TXA produces pain by inhibiting GABAA and glycine receptors in the spinal dorsal horn.

View Article: PubMed Central - PubMed

Affiliation: Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, 951-8510 Japan.

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.

No MeSH data available.


Related in: MedlinePlus