The antinociceptive effect of intrathecal kynurenic acid and its interaction with endomorphin-1 in rats

Kekesi, Gabriella; Joó, Gabriella; Csullog, Emese; Dobos, Ildikó; Klimscha, Walter; Tóth, Kálmán; Benedek, György; Horváth, Gyöngyi

doi:10.1016/s0014-2999(02)01787-9

Cited by 21 publications

(17 citation statements)

References 20 publications

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“…Therefore, it can be proposed that effects on the thermoregulatory sympathetic efferents might lead to the observed changes of the core temperature after morphine administration. Since the co-administration of NMDA receptor antagonists and opioid receptor agonists can produce enhanced antinociception (Kekesi et al, 2002), they are antagonists in terms of their effect on the core temperature; thus, the combination of these ligands may be beneficial for pain therapy to prevent thermoregulatory side effects of morphine.…”

Section: Discussionmentioning

confidence: 99%

Telemetry monitoring for non-invasive assessment of changes in core temperature after spinal drug administration in freely moving rats

Safrany-Fark

Petrovszki

Kekesi

et al. 2015

Journal of Pharmacological and Toxicological Methods

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Section: Discussionmentioning

confidence: 99%

Telemetry monitoring for non-invasive assessment of changes in core temperature after spinal drug administration in freely moving rats

Safrany-Fark

Petrovszki

Kekesi

et al. 2015

Journal of Pharmacological and Toxicological Methods

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“…The composition of nACSF was (in mM): 122 NaCl, 24 NaHCO 3 , 2.5 CaCl 2 , 3 KCl, 1 MgSO 4 , and 12 D-glucose. The composition of mACSF was (in mM): 118 NaCl, 24 NaHCO 3 , 1.5 CaCl 2 , 3 KCl, 5 MgCl 2 , 1.4 NaH 2 PO 4 , 1.3 MgSO 4 , 25 D-glucose, and 1 M kynurenic acid; the latter is a nonspecific blocker of glutamate transmission (Kekesi et al 2002). Both kinds of ACSF were saturated with 95% O 2 -5% CO 2 , and maintained at pH 7.4.…”

Section: Drugs and Solutionmentioning

confidence: 99%

Persistent Sodium and Calcium Currents Cause Plateau Potentials in Motoneurons of Chronic Spinal Rats

Bennett

2003

Journal of Neurophysiology

266

417

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After chronic spinal cord injury motoneurons exhibit large plateau potentials (sustained depolarizations triggered by brief inputs) that play a primary role in the development of muscle spasms and spasticity (Bennett et al. 2001a , b ). The present study examined the voltage-gated persistent inward currents (PICs) underlying these plateaus. Adult rats were spinalized at the S2 sacral spinal level and after 2 mo, when spasticity developed, intracellular recordings were made from motoneurons below the injury. For recording, the whole sacrocaudal spinal cord was removed and maintained in vitro in normal artificial cerebral spinal fluid (nACSF), without application of neuromodulators. During a slow triangular voltage-clamp command (ramp) a PIC was activated with a threshold of –54.2 ± 4.8 mV (similar to plateau threshold), with a peak current of 2.88 ± 0.95 nA and produced a pronounced negative-slope region in the V–I relation. This PIC was in part mediated by Cav1.3 L-type calcium channels because it was low threshold and significantly reduced by 10 to 20 μM nimodipine or 400 μM Cd2+. The PIC that remained during a calcium channel blockade (in Cd2+) was completely and rapidly blocked by tetrodotoxin (TTX; 0.5 to 2 μM), and thus was a TTX-sensitive persistent sodium current. This persistent sodium current was activated rapidly about 7 mV below the spike threshold (spike threshold –46.1 ± 4.5 mV), contributed approximately 1/2 of the initial peak of the total PIC, inactivated partly to contribute only approximately 1/3 of the sustained PIC (at 5 to 10 s), and deactivated rapidly with hyperpolarization (<50 ms). When TTX was added to the bath first, the nimodipine-sensitive persistent calcium current (L-type) was seen in isolation; it was slowly activated (>250 ms), had a low but variable threshold (either slightly above or below the spike threshold), contributed the other approximately 1/2 of the initial peak of the total PIC (before TTX), did not usually inactivate with time (contributed approximately two-thirds of the sustained PIC), and deactivated slowly with hyperpolarization to rest (in >300 ms). In summary, low-threshold persistent calcium (Cav1.3) and sodium currents spontaneously develop in motoneurons of chronic spinal rats and these enable large, rapidly activated plateaus that ultimately lead to spasticity.

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“…r (-) [126] Thermal hyperalgesia, carrageenan i.th. r (+) (-) [195] Kynurenic acid IC50 = 7.9 µM [194] l Thermal hyperalgesia, carrageenan--µ-opiod attenuation i.th. r (+) (+) [195] Thermal hyperalgesia, carrageenan i.th.…”

Section: Competitive Glycine Site Antagonistsmentioning

confidence: 99%

“…r (+) (-) [195] Kynurenic acid IC50 = 7.9 µM [194] l Thermal hyperalgesia, carrageenan--µ-opiod attenuation i.th. r (+) (+) [195] Thermal hyperalgesia, carrageenan i.th. r (+) (+) [ AZ-2-PQT, is a potent and selective full antagonist at the glycine site [197].…”

Section: Competitive Glycine Site Antagonistsmentioning

confidence: 99%

N-Methyl-D-Aspartate Receptor (NMDA) Antagonists as Potential Pain Therapeutics

Brown¹,

Krupp²

2006

CTMC

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NMDA receptors are known to be involved in nociceptive transmission and pain processing. Many structurally diverse NMDA antagonists have been reported to have activity in both animal models and clinical models of neuropathic pain. Untoward side effects such as ataxia and sedation have severely limited the clinical uses of this class of potential therapeutics. However, antagonists at the glycine-site, NR2B sites and weak-binding channel blockers have demonstrated an improved side effect profile in animal models of pain. These types of compounds may hold potential promise for future pain therapies. This review covers reported pain data surrounding representative examples of NMDA antagonists and provides a current assessment of potential clinical utility.

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The antinociceptive effect of intrathecal kynurenic acid and its interaction with endomorphin-1 in rats

Cited by 21 publications

References 20 publications

Telemetry monitoring for non-invasive assessment of changes in core temperature after spinal drug administration in freely moving rats

Telemetry monitoring for non-invasive assessment of changes in core temperature after spinal drug administration in freely moving rats

Persistent Sodium and Calcium Currents Cause Plateau Potentials in Motoneurons of Chronic Spinal Rats

N-Methyl-D-Aspartate Receptor (NMDA) Antagonists as Potential Pain Therapeutics

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