Voltage-Gated Calcium Channels as Targets for the Treatment of Chronic Pain

McGivern, Joseph G.; McDonough, Stefan I.

doi:10.2174/1568007043336743

Cited by 72 publications

(28 citation statements)

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“…There are substantial experimental evidences that argues in favor of the participation of voltage-gated Ca 2+ channels as key elements in the transmission of pain signals (McGivern and McDonough, 2004;Lee et al, 2005;Chung et al, 2008;Zamponi et al, 2009;Perret and Luo, 2009). Knowing that eugenol is related to capsaicin in terms of chemical structure and that capsaicin has been demonstrated to inhibit high voltage-gated Ca 2+ channels (Petersen et al, 1989;Bleakman et al, 1990), these information combined have motivated studies to investigate whether eugenol would interact with high voltage-gated Ca 2+ channels.…”

Section: Constituents Of Essential Oils That Acts In the Central And mentioning

confidence: 99%

Essential oils components as a new path to understand ion channel molecular pharmacology

2011

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Section: Constituents Of Essential Oils That Acts In the Central And mentioning

confidence: 99%

Essential oils components as a new path to understand ion channel molecular pharmacology

2011

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“…Pharmacology and genetic studies showed that Ca v 2.2 inhibiting activity was an effective way to manage or alleviate symptoms of inflammatory, chronic and neuropathic pain (Kerr et al, 1988; Gohil et al, 1994; Saegusa et al, 2001, 2002; McGivern and McDonough, 2004; McGivern, 2006; Altier et al, 2007; Trang et al, 2015). Ca v 2.2 antagonists have therefore long been considered as potential analgesics (Hazelhoff et al, 1982; Mathela et al, 2005; La et al, 2008; Yamamoto and Takahara, 2009; Pajouhesh et al, 2010; Schmidtkco et al, 2010; Swensen et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Valepotriates From the Roots and Rhizomes of Valeriana jatamansi Jones as Novel N-Type Calcium Channel Antagonists

Fan

Jiang²,

Liu

et al. 2018

Front. Pharmacol.

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The roots and rhizomes of Valeriana jatamansi have long been used as folk medicine in Asia and usually named as “Zhizhuxiang” in Chinese for the treatment of abdominal distention and pain. However, its active ingredients and molecular targets for treatment of abdominal pain remain unrevealed. Inhibitors of Ca v 2.2 N-type voltage-gated calcium channels (VGCCs) are actively sought after for their potential in treating pain, especially chronic pain. As far as we know, the method used for seeking analgesic active ingredient from plant material has rarely been reported. The analgesic potentials of the EtOH extract (0.01 mg/ml) of the roots and rhizomes of V. jatamansi and its EtOAc, n -BuOH and H 2 O soluble parts (0.01 mg/ml, respectively) were tested herein on Ca v 2.2, using whole-oocyte recordings in vitro by tow-electrode voltage clamp. The results indicated that the EtOAc-soluble part exhibited the most potent inhibition of Ca v 2.2 peak current (20 mv). The EtOAc-soluble part was then subjected to silica gel column chromatography (CC) and giving 9 fractions. Phytochemical studies were carried out by repeated CC and extensive spectroscopic analyses after the fraction (0.01 mg/ml) was identified to be active and got seventeen compounds ( 1 – 17 ). All isolates were then sent for further bioactive verification ( 1 and 3 at concentration of 10 μM, others at 30 μM). In addition, the selectivity of the active compounds 1 and 3 were tested on various ion channels including Ca v 1.2, Ca v 2.1 and Ca v 3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. The results indicated that compound 1 and 3 (an abundant compound) inhibited Ca v 2.2 with an EC 50 of 3.3 and 4.8 μM, respectively, and had weaker or no effect on Ca v 1.2, Ca v 2.1 and Ca v 3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. Compounds 1 and 3 appear to act as allosteric modulators rather than pore blockers of Ca v 2.2, which may play crucial role in attenuating nociception. The results of present research indicated that the ethnopharmacological utilization of V. jatamansi for relieving the abdominal distention and pain may mediate through Ca v 2.2 channel. Our work is the first demonstration of inhibition of Ca v 2.2 by iridoids, which may provide a fresh source for finding new analgesics.

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“…39 Protein SUMOylation has been reported to modulate neurotransmitter release 36 perhaps via N-type calcium channels that, in turn, are modulated by CRMP2. In summary, SUMO regulation of CRMP2/CaV2.2 signaling may have important implications for chronic pain because CaV2.2 channels are genetically 40,41 and clinically 28,42,43 validated targets for pain management. Future work will also investigate whether SUMOylation of CRMP2 affects its other functions, as well as how it regulates its other interactions.…”

Section: Discussionmentioning

confidence: 99%