pH-dependent inhibition of tetrodotoxin-resistant Na+ channels by diclofenac in rat nociceptive neurons

Nakamura, Michiko; Jang, Il‐Sung

doi:10.1016/j.pnpbp.2015.07.003

Cited by 8 publications

(5 citation statements)

References 40 publications

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“…Furthermore, the patient did not complain of any pain at the injection site, as expected by the extent of the putative muscle injury visualized by MR imaging. The contradiction between the impressive morphological and laboratory signs and lack of clinical symptoms might also result from long-lasting tissue deposition of diclofenac, which is known to exert local anesthetic effects [13, 14]. In that context, it should be reminded that every single rat in our previous experimental study showed a massive T2 enhancement at the injection site [5].…”

Section: Discussionmentioning

confidence: 99%

Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging

Probst

Kühn

Modeß

et al. 2017

Drug Saf - Case Rep

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Intramuscular injection of diclofenac is still frequently practiced, although there is ample evidence that the risk of local tissue intolerability is highly underestimated. The aim of this study was to evaluate local toxicity in a patient using magnetic resonance imaging. A patient who gave written informed consent received a medically indicated intramuscular administration of diclofenac 75 mg/2 mL. Simultaneously with magnetic resonance imaging of the depot, a clinical–chemical evaluation and quantification of diclofenac in plasma was performed. A manifold enhancement of the T2-weighted magnetic resonance signal was observed in a muscle area of approximately 60 mL volume, with maximum signal intensity 30 min after injection, the time of maximum diclofenac plasma exposure. Plasma creatine kinase activity was elevated approximately sixfold within 8 h and normalized within 1 week, whereas the magnetic resonance enhancement disappeared within 5 weeks. Interestingly, the patient did not complain about any clinical symptoms at the injection site. Asymptomatic tissue injury after intramuscular injection of diclofenac, caused by intramuscular dosing, can be reliably evaluated by magnetic resonance imaging and should be applied early during the development of parenteral dosage forms. Clinical Trials Registration Number: BB130/16 (Ethics Committee of the University Medicine Greifswald).

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Section: Discussionmentioning

confidence: 99%

Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging

Probst

Kühn

Modeß

et al. 2017

Drug Saf - Case Rep

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“…Clonidine produced both Aα-fiber and C-fiber CAP amplitude reductions (refer to Section 3.4). Furthermore, many researchers have demonstrated a suppression by NSAIDs [56,63,329], lidocaine, and α 2 -adrenoceptor agonists [145] of TTXresistant voltage-dependent sodium channels, which may be involved in slow-conducting CAP production. Knocking down Nav1.8 channels resistant to TTX reportedly resulted in suppressed pain associated with neuropathy or inflammation in rats [330].…”

Section: Discussionmentioning

confidence: 99%

“…This order partly resembled the order for sodium channel suppression in DRG neurons (diclofenac > flufenamic acid > indomethacin > aspirin; [56]) and in cardiomyocytes (diclofenac > naproxen ≥ ibuprofen; [59]) in rats. Diclofenac at 0.3 mM reduced the TTX-resistant sodium channel current amplitudes by about 20% in trigeminal ganglion neurons in rats [63]. Flufenamic acid and tolfenamic acid at 0.1 mM reduced TTX-resistant Nav1.8 channel current amplitudes with the extents of approximately 30 and 30%, respectively [64].…”

Section: Nsaidsmentioning

confidence: 97%

Inhibitory Actions of Clinical Analgesics, Analgesic Adjuvants, and Plant-Derived Analgesics on Nerve Action Potential Conduction

Kumamoto

2022

Encyclopedia

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The action potential (AP) conduction in nerve fibers plays a crucial role in transmitting nociceptive information from the periphery to the cerebral cortex. Nerve AP conduction inhibition possibly results in analgesia. It is well-known that many analgesics suppress nerve AP conduction and voltage-dependent sodium and potassium channels that are involved in producing APs. The compound action potential (CAP) recorded from a bundle of nerve fibers is a guide for knowing if analgesics affect nerve AP conduction. This entry mentions the inhibitory effects of clinically used analgesics, analgesic adjuvants, and plant-derived analgesics on fast-conducting CAPs and voltage-dependent sodium and potassium channels. The efficacies of their effects were compared among the compounds, and it was revealed that some of the compounds have similar efficacies in suppressing CAPs. It is suggested that analgesics-induced nerve AP conduction inhibition may contribute to at least a part of their analgesic effects.

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“…Clonidine inhibited both Aα-fiber and C-fiber CAPs (see Section 3.1 ). Moreover, many investigators have reported an inhibition by lidocaine, α 2 -adrenoceptor agonists [ 148 ] and NSAIDs [ 108 , 115 , 293 ] of TTX-resistant voltage-gated Na + channels (see Table 2 , Table 3 and Table 5 ) that may be involved in producing slow-conducting CAPs. It has been reported that the knockdown of TTX-resistant Nav1.8 channels results in inhibition of neuropathic and inflammatory pain in rats [ 294 ].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding rank order among NSAIDs, the order for CAP inhibition at 0.5 mM was flufenamic acid > diclofenac > indomethacin >> aspirin = naproxen = ibuprofen [21]; this was in part similar to those for Na + channel inhibition in rat cardiomyocytes (diclofenac > naproxen ≥ ibuprofen; [111]) and also in rat DRG neurons (diclofenac > flufenamic acid > indomethacin > aspirin; [108]). With respect to TTX-resistant Na + channels, diclofenac at 0.3 mM reduced peak current amplitudes by about 20% in rat trigeminal ganglion neurons [115]; Nav1.8 channel currents were inhibited by flufenamic acid and tolfenamic acid (current amplitude reduction: ca. 30 and 30%, respectively, at 0.1 mM; [116]).…”

Section: Nsaidsmentioning

confidence: 99%

Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants—Possible Involvement in Pain Alleviation

Kumamoto

2020

Pharmaceuticals

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Nociceptive information is transmitted from the periphery to the cerebral cortex mainly by action potential (AP) conduction in nerve fibers and chemical transmission at synapses. Although this nociceptive transmission is largely inhibited at synapses by analgesics and their adjuvants, it is possible that the antinociceptive drugs inhibit nerve AP conduction, contributing to their antinociceptive effects. Many of the drugs are reported to inhibit the nerve conduction of AP and voltage-gated Na+ and K+ channels involved in its production. Compound action potential (CAP) is a useful measure to know whether drugs act on nerve AP conduction. Clinically-used analgesics and analgesic adjuvants (opioids, non-steroidal anti-inflammatory drugs, α2-adrenoceptor agonists, antiepileptics, antidepressants and local anesthetics) were found to inhibit fast-conducting CAPs recorded from the frog sciatic nerve by using the air-gap method. Similar actions were produced by antinociceptive plant-derived chemicals. Their inhibitory actions depended on the concentrations and chemical structures of the drugs. This review article will mention the inhibitory actions of the antinociceptive compounds on CAPs in frog and mammalian peripheral (particularly, sciatic) nerves and on voltage-gated Na+ and K+ channels involved in AP production. Nerve AP conduction inhibition produced by analgesics and analgesic adjuvants is suggested to contribute to at least a part of their antinociceptive effects.

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pH-dependent inhibition of tetrodotoxin-resistant Na+ channels by diclofenac in rat nociceptive neurons

Cited by 8 publications

References 40 publications

Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging

Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging

Inhibitory Actions of Clinical Analgesics, Analgesic Adjuvants, and Plant-Derived Analgesics on Nerve Action Potential Conduction

Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants—Possible Involvement in Pain Alleviation

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