Abstract
Inflammation is the body’s mechanism to trigger the immune system, thereby preventing
bacteria and viruses from manifesting their toxic effect. Inflammation plays a vital role in regulating
inflammatory mediator levels to initiate the wound healing process depending on the nature of the
stimuli. This process occurs due to chemical release from white blood cells by elevating blood flow
to the site of action, leading to redness and increased body temperature. Currently, there are numerous
Non-steroidal anti-inflammatory drugs (NSAIDs) available, but these drugs are reported with
adverse effects such as gastric bleeding, progressive kidney damage, and increased risk of heart attacks
when prolonged use. For such instances, alternative options need to be adopted. The introduction
of voltage-gated ion channel blockers can be a substantial alternative to mask the side effects of
these currently available drugs. Chronic inflammatory disorders such as rheumatoid and osteoarthritis,
cancer and migraine, etc., can cause dreadful pain, which is often debilitating for the patient.
The underlying mechanism for both acute and chronic inflammation involves various complex receptors,
different types of cells, receptors, and proteins. The working of voltage-gated sodium and
calcium channels is closely linked to both inflammatory and neuropathic pain. Certain drugs such as
carbamazepine and gabapentin, which are ion channel blockers, have greater pharmacotherapeutic
activity for sodium and calcium channel blockers for the treatment of chronic inflammatory pain
states. This review intends to provide brief information on the mechanism of action, latest clinical
trials, and applications of these blockers in treating inflammatory conditions.
Keywords:
Voltage-gated ion channel blockers, inflammation, inflammatory conditions, sodium channel blockers, potassium channel blockers, calcium channel blockers.
Graphical Abstract
[5]
Madden JA, Rusch NJ. Electrophysiology of vascular smooth muscle. Heart Physiol Pathophysiol 2001; 213-27.
[20]
Ren D, Navarro B, Xu H, Yue L, Shi Q, Clapham DE. A prokaryotic voltage-gated sodium channel. Science (1979) 2001; 294(5550): 2372-5.
[54]
Bidaud I, Mezghrani A, Swayne LA, Monteil A, Lory P. Voltage-gated calcium channels in genetic diseases. Biochimica et Biophysica Acta (BBA) -. Mol Cell Res 2006; 1763(11): 1169-74.
[62]
Taddei S, Bruno RM. Calcium channel blockers. Encyclopedia of Endocrine Diseases 2018; 689-95.
[67]
Morais-Cabral JH, Zhou Y, MacKinnon R. Energetic optimization of ion conduction rate by the K+ selectivity filter. Nature 2001; 414(6859): 37-42.
[68]
Zhou Y, Morais CJH, Kaufman A, Mackinnon R. Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 Å resolution. Nature 2001; 414(6859): 43-8.
[83]
Lü Q, Miller C. Silver as a probe of pore-forming residues in a potassium channel. Science 1995; 268(5208): 304-7.
[87]
Gründer S, Thiemann A, Pusch M, Jentsch TJ. Regions involved in the opening of CIC-2 chloride channel by voltage and cell volume. Nature 1992; 360(6406): 759-62.
[91]
Jurenka JS. Jurenka. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research. Altern Med Rev 2009; 14(2): 141-53.
[92]
Aggarwal B, Chandra Bharti A. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res 2003; 23(1A): 363-98.
[93]
Huang MT, Lysz T, Ferraro T, Abidi TF, Laskin JD, Conney AH. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res 1991; 51(3): 813-9.
[94]
Cho J-W, Lee K-S, Kim C-W. Curcumin attenuates the expression of IL-1beta, IL-6, and TNF-alpha as well as cyclin E in TNF-alpha-treated HaCaT cells; NF-kappaB and MAPKs as potential upstream targets. Int J Mol Med 2007; 19(3): 469-74.
[101]
Truini A, Garcia-Larrea L, Cruccu G. Reappraising neuropathic pain in humans-how symptoms help disclose mechanisms. Nature Reviews Neurology 2013; 9(10): 572-82.