Limits...
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) enhances ERK activation in the superficial dorsal horn of the spinal cord.Under Krebs solution, few neurons are positive for pERK, an indicator of nociceptive stimulation, in slices of the superficial dorsal horn of the spinal cord (n = 7). In contrast, TXA (1 mM, 10 min) significantly increases the number of pERK-positive neurons (n = 7). ERK activation was quantified by counting the number of pERK-labeled neurons in the superficial dorsal horn in control and TXA groups. Filled arrowheads indicate pERK-positive neurons. Bar = 50 μm. The data are given as mean ± SD. **P < 0.01 by unpaired t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4544020&req=5

f6: Tranexamic acid (TXA) enhances ERK activation in the superficial dorsal horn of the spinal cord.Under Krebs solution, few neurons are positive for pERK, an indicator of nociceptive stimulation, in slices of the superficial dorsal horn of the spinal cord (n = 7). In contrast, TXA (1 mM, 10 min) significantly increases the number of pERK-positive neurons (n = 7). ERK activation was quantified by counting the number of pERK-labeled neurons in the superficial dorsal horn in control and TXA groups. Filled arrowheads indicate pERK-positive neurons. Bar = 50 μm. The data are given as mean ± SD. **P < 0.01 by unpaired t-test.

Mentions: To obtain spatial information on neuronal excitation in the spinal dorsal horn, we investigated the effect of TXA on neuronal pERK expression, which is indicative of pain. There were very few pERK-positive neurons in the superficial dorsal horn of control spinal cord slices when perfused with standard Krebs solution. However, following application of TXA to the perfusate for 10 min, the number of pERK-positive neurons significantly increased from 5.2 ± 1.4 to 13.1 ± 2.5 (n = 7, P < 0.01, Fig. 6). These results suggested that TXA enhances ERK activation.


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) enhances ERK activation in the superficial dorsal horn of the spinal cord.Under Krebs solution, few neurons are positive for pERK, an indicator of nociceptive stimulation, in slices of the superficial dorsal horn of the spinal cord (n = 7). In contrast, TXA (1 mM, 10 min) significantly increases the number of pERK-positive neurons (n = 7). ERK activation was quantified by counting the number of pERK-labeled neurons in the superficial dorsal horn in control and TXA groups. Filled arrowheads indicate pERK-positive neurons. Bar = 50 μm. The data are given as mean ± SD. **P < 0.01 by unpaired t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Tranexamic acid (TXA) enhances ERK activation in the superficial dorsal horn of the spinal cord.Under Krebs solution, few neurons are positive for pERK, an indicator of nociceptive stimulation, in slices of the superficial dorsal horn of the spinal cord (n = 7). In contrast, TXA (1 mM, 10 min) significantly increases the number of pERK-positive neurons (n = 7). ERK activation was quantified by counting the number of pERK-labeled neurons in the superficial dorsal horn in control and TXA groups. Filled arrowheads indicate pERK-positive neurons. Bar = 50 μm. The data are given as mean ± SD. **P < 0.01 by unpaired t-test.
Mentions: To obtain spatial information on neuronal excitation in the spinal dorsal horn, we investigated the effect of TXA on neuronal pERK expression, which is indicative of pain. There were very few pERK-positive neurons in the superficial dorsal horn of control spinal cord slices when perfused with standard Krebs solution. However, following application of TXA to the perfusate for 10 min, the number of pERK-positive neurons significantly increased from 5.2 ± 1.4 to 13.1 ± 2.5 (n = 7, P < 0.01, Fig. 6). These results suggested that TXA enhances ERK activation.

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