Novel sodium channel antagonists in the treatment of neuropathic pain

ABSTRACT

Introduction: Effective and safe drugs for the treatment of neuropathic pain are still an unmet clinical need. Neuropathic pain, caused by a lesion or disease that affects the somatosensory system, is a debilitating and hampering condition that has a great economic cost and, above all, a tremendous impact on the quality of life. Sodium channels are one of the major players in generating and propagating action potentials. They represent an appealing target for researchers involved in the development of new and safer drugs useful in the treatment of neuropathic pain. The actual goal for researchers is to target sodium channels selectively to stop the abnormal signaling that characterizes neuropathic pain while leaving normal somatosensory functions intact.

Areas covered: This review covers the most recent publications regarding sodium channel blockers and their development as new treatments for neuropathic pain. The main areas discussed are the natural sources of new blockers, such as venom extracts and the recent efforts from many pharmaceutical companies in the field.

Expert opinion: There have been serious efforts by both the pharmaceutical industry and academia to develop new and safer therapeutic options for neuropathic pain. A number of different strategies have been undertaken; the main efforts directed towards the identification of selective blockers starting from both natural products or screening chemical libraries. At this time, researchers have identified and characterized selective compounds against Na_V1.7 or Na_V1.8 voltage-gated sodium channels but only time will tell if they reach the market.

KEYWORDS:

• Neuropathic pain
• pain
• sodium channel blockers
• sodium channel isoforms

Financial and competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Article highlights

• Neuropathic pain affects millions of people worldwide and it is still an unmet clinical issue.

• Voltage-gated sodium channels are important players in the transmission of painful stimuli and a suitable target for the management of neuropathic pain.

• In the past years we assisted at the disclosure of a great number of patent applications by pharmaceutical companies. This allowed to have a better idea of the ‘state of the art’ in this field.

• Some researchers focused their attention on natural products, in particular peptides extracted from venoms. These peptides represent very useful pharmacological tools however, the problems that affect their adminisration could hamper their progression into marketable drugs.

• The major efforts were spent in reaching subtype selectivity, in particular over Na_V1.7 and Na_V1.8 isoforms. Many important results have been reached but, at this point in time, it is premature to forecast how many of these selective blockers could reach the market.This box summarizes key points contained in the article.

ORCID

Mirko Rivara http://orcid.org/0000-0001-6809-0020

Valentina Zuliani http://orcid.org/0000-0002-2242-3317