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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

Model of the spinal dorsal horn circuit underlying the mechanism of tranexamic acid (TXA)-produced pain.TXA directly inhibits GABA and glycine receptors located on postsynaptic sites of the recorded SG neurons. TXA also inhibits GABAA and glycine receptors located on postsynaptic sites on excitatory interneurons. This leads to increased glutamate release from the excitatory interneurons to the recorded SG neurons located postsynaptically, resulting in increased spontaneous activity. SG, substantia gelatinosa; DRG, dorsal root ganglion.
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f7: Model of the spinal dorsal horn circuit underlying the mechanism of tranexamic acid (TXA)-produced pain.TXA directly inhibits GABA and glycine receptors located on postsynaptic sites of the recorded SG neurons. TXA also inhibits GABAA and glycine receptors located on postsynaptic sites on excitatory interneurons. This leads to increased glutamate release from the excitatory interneurons to the recorded SG neurons located postsynaptically, resulting in increased spontaneous activity. SG, substantia gelatinosa; DRG, dorsal root ganglion.

Mentions: Given this, we propose the following model circuit for the underlying mechanism of TXA in the spinal dorsal horn (Fig. 7). TXA directly inhibits GABAA and glycine receptors located on postsynaptic sites of the recorded SG neurons, resulting in increased neuronal excitability. In addition, TXA inhibits GABAA and glycine receptors postsynaptically located on the excitatory interneurons, thus inducing excitability. Consequently, TXA leads to increased glutamate release from presynaptic excitatory interneurons to SG neurons. We propose that these mechanisms could produce pain.


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)

Model of the spinal dorsal horn circuit underlying the mechanism of tranexamic acid (TXA)-produced pain.TXA directly inhibits GABA and glycine receptors located on postsynaptic sites of the recorded SG neurons. TXA also inhibits GABAA and glycine receptors located on postsynaptic sites on excitatory interneurons. This leads to increased glutamate release from the excitatory interneurons to the recorded SG neurons located postsynaptically, resulting in increased spontaneous activity. SG, substantia gelatinosa; DRG, dorsal root ganglion.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Model of the spinal dorsal horn circuit underlying the mechanism of tranexamic acid (TXA)-produced pain.TXA directly inhibits GABA and glycine receptors located on postsynaptic sites of the recorded SG neurons. TXA also inhibits GABAA and glycine receptors located on postsynaptic sites on excitatory interneurons. This leads to increased glutamate release from the excitatory interneurons to the recorded SG neurons located postsynaptically, resulting in increased spontaneous activity. SG, substantia gelatinosa; DRG, dorsal root ganglion.
Mentions: Given this, we propose the following model circuit for the underlying mechanism of TXA in the spinal dorsal horn (Fig. 7). TXA directly inhibits GABAA and glycine receptors located on postsynaptic sites of the recorded SG neurons, resulting in increased neuronal excitability. In addition, TXA inhibits GABAA and glycine receptors postsynaptically located on the excitatory interneurons, thus inducing excitability. Consequently, TXA leads to increased glutamate release from presynaptic excitatory interneurons to SG neurons. We propose that these mechanisms could produce pain.

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