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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) increases the number of action potentials in dorsal horn neurons.TXA (1 mM) significantly increases the number of action potentials induced by current injection (100 pA, 1000 ms) in all recorded neurons (n = 7). *P < 0.05 by paired t-test.
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f4: Tranexamic acid (TXA) increases the number of action potentials in dorsal horn neurons.TXA (1 mM) significantly increases the number of action potentials induced by current injection (100 pA, 1000 ms) in all recorded neurons (n = 7). *P < 0.05 by paired t-test.

Mentions: Given that TXA decreases inhibition in SG neurons, it may also increase the potential for neuronal excitation. We therefore investigated action potential discharge activity in current-clamp mode. TXA significantly increased the number of action potentials from 6.9 ± 2.6 to 12.0 ± 4.8 (n = 7, P < 0.05 by paired t-test) when a depolarizing current was injected into the recorded neurons (Fig. 4A,B).


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) increases the number of action potentials in dorsal horn neurons.TXA (1 mM) significantly increases the number of action potentials induced by current injection (100 pA, 1000 ms) in all recorded neurons (n = 7). *P < 0.05 by paired t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Tranexamic acid (TXA) increases the number of action potentials in dorsal horn neurons.TXA (1 mM) significantly increases the number of action potentials induced by current injection (100 pA, 1000 ms) in all recorded neurons (n = 7). *P < 0.05 by paired t-test.
Mentions: Given that TXA decreases inhibition in SG neurons, it may also increase the potential for neuronal excitation. We therefore investigated action potential discharge activity in current-clamp mode. TXA significantly increased the number of action potentials from 6.9 ± 2.6 to 12.0 ± 4.8 (n = 7, P < 0.05 by paired t-test) when a depolarizing current was injected into the recorded neurons (Fig. 4A,B).

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