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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

Tranexamic acid (TXA) inhibits the amplitude and decreases the integrated area of currents induced by exogenous GABA or glycine.(A) TXA (1 mM, 2 min) significantly decreases the amplitude and integrated area of the current elicited by exogenous application of GABA (1 mM, 30 s; n = 7). (B) TXA (1 mM, 2 min) significantly decreases the amplitude and integrated area of the current elicited by exogenous application of glycine (1 mM, 30 s; n = 7). Holding potential = 0 mV for all recordings. **P < 0.01 by paired t-test.
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f3: Tranexamic acid (TXA) inhibits the amplitude and decreases the integrated area of currents induced by exogenous GABA or glycine.(A) TXA (1 mM, 2 min) significantly decreases the amplitude and integrated area of the current elicited by exogenous application of GABA (1 mM, 30 s; n = 7). (B) TXA (1 mM, 2 min) significantly decreases the amplitude and integrated area of the current elicited by exogenous application of glycine (1 mM, 30 s; n = 7). Holding potential = 0 mV for all recordings. **P < 0.01 by paired t-test.

Mentions: Next, we investigated the effects of TXA on the current induced by exogenously administered GABA or glycine (1 mM, 30 s) in SG neurons, in the presence of TTX to isolate postsynaptic actions. In the presence of TXA, the mean amplitude of the elicited GABA current decreased to 57.4 ± 12.2% of control, and the integrated area decreased to 40.0 ± 12.1% of control (n = 7, P < 0.01; Fig. 3A).


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)

Tranexamic acid (TXA) inhibits the amplitude and decreases the integrated area of currents induced by exogenous GABA or glycine.(A) TXA (1 mM, 2 min) significantly decreases the amplitude and integrated area of the current elicited by exogenous application of GABA (1 mM, 30 s; n = 7). (B) TXA (1 mM, 2 min) significantly decreases the amplitude and integrated area of the current elicited by exogenous application of glycine (1 mM, 30 s; n = 7). Holding potential = 0 mV for all recordings. **P < 0.01 by paired t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Tranexamic acid (TXA) inhibits the amplitude and decreases the integrated area of currents induced by exogenous GABA or glycine.(A) TXA (1 mM, 2 min) significantly decreases the amplitude and integrated area of the current elicited by exogenous application of GABA (1 mM, 30 s; n = 7). (B) TXA (1 mM, 2 min) significantly decreases the amplitude and integrated area of the current elicited by exogenous application of glycine (1 mM, 30 s; n = 7). Holding potential = 0 mV for all recordings. **P < 0.01 by paired t-test.
Mentions: Next, we investigated the effects of TXA on the current induced by exogenously administered GABA or glycine (1 mM, 30 s) in SG neurons, in the presence of TTX to isolate postsynaptic actions. In the presence of TXA, the mean amplitude of the elicited GABA current decreased to 57.4 ± 12.2% of control, and the integrated area decreased to 40.0 ± 12.1% of control (n = 7, P < 0.01; Fig. 3A).

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