Cellular and molecular mechanisms driving neuropathic pain: recent advancements and challenges

Valencia Fernandes, Dilip Sharma, Shivani Vaidya, P. A. Shantanu, Yun Guan, Kiran Kalia, Vinod Tiwari

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: Current pharmacotherapeutics for neuropathic pain offer only symptomatic relief without treating the underlying pathophysiology. Additionally, they are associated with various dose-limiting side effects. Pain research in the past few decades has revolved around the role of oxidative-nitrosative stress, protein kinases, glial cell activation, and inflammatory signaling cascades but has failed to produce specific and effective therapies. Areas covered: This review focuses on recent advances in cellular and molecular mechanisms of neuropathic pain that may be translated into future therapies. We discuss emerging targets such as WNT signaling mechanisms, the tetrahydrobiopterin pathway, Mrg receptors, endogenous lipid mediators, micro-RNAs and their roles in pain regulation. Recent evidence is also presented regarding genetic and epigenetic mechanisms of pain modulation. Expert opinion: During chronic neuropathic pain, maladaptation occurs in the peripheral and central nervous systems, including a shift in microglial phenotype from a surveillance state to an activated state. Microglial activation leads to an altered expression of cell surface proteins, growth factors, and intracellular signaling molecules that contribute to development of a neuroinflammatory cascade and chronic pain sensitization. Specific targeting of these cellular and molecular mechanisms may provide the key to development of effective neuropathic pain therapies that have minimal side effects.

Original languageEnglish (US)
Pages (from-to)131-142
Number of pages12
JournalExpert opinion on therapeutic targets
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2018

Keywords

  • Mrg receptors
  • Neuropathic pain
  • WNT signaling
  • epigenetics
  • microRNA
  • purinergic
  • tetrahydrobiopterin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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