Topical drug therapeutics for neuropathic pain

ABSTRACT

Introduction: Neuropathic pain (NP) is a particularly severe and intractable chronic condition that is not well treated by commonly recommended systemic pharmacological therapies, partly due to dose-limiting side effects or adverse events. The use of topical therapeutics for NP is growing and benefits from the reduced potential for adverse effects, as well as the ability to directly target peripheral pathological processes.

Areas covered: The current review defines and describes the limitations of various commonly prescribed systemic pharmacological therapies for NP. It also provides a justification for increased research aimed at developing topical therapeutics for NP, particularly localized and peripheral NP. The review discusses the various classes of topical treatments used for NP, including agents that: block sensory inputs; activate inhibitory systems; provide mechanism-based therapeutics; are used in mucosal tissues; and include combinations that produce multimodal therapeutic effects.

Expert opinion: There are arguments that the current topical therapeutics for NP rely too heavily on the use of local anesthetics and capsaicinoids, and more research is certainly needed on topical therapies that are multimodal and/or are targeted at the peripheral sources of pathology. The potential for novel topical therapeutics may be enhanced by further research on topical co-drugs, drug-drug salts, co-crystals and hydrates, and ionic liquids.

KEYWORDS:

• Α₂-adrenergic agents
• anticonvulsants
• antidepressants
• capsaicinoids
• local anesthetics
• multimodal therapy
• nitric oxide donors
• NMDA antagonists
• NSAIDs
• opioids

Declaration of interest

The author has a pending patent of the use of topical treatments for NP, and is a partner in SynergesX Pharma, a company developing synergistic topical combinations for CRPS and NP. He has no other 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 apart from those disclosed.

Reviewer disclosures

One referee is a patent holder on (1) topical phenytoin for use in the treatment of peripheral neuropathic pain and (2) a topical pharmaceutical composition containing phenytoin and a (co-)analgesic for the treatment of chronic pain.

Additional information

Funding

The author has received grant funding from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, and the Louise and Alan Edwards Foundation.