Pharmacologic agents directed at the treatment of pain associated with maladaptive neuronal plasticity

Joseph V. Pergolizzi, Giustino Varrassi, Peter Magnusson, Frank Breve, Robert B. Raffa, Paul J. Christo, Maninder Chopra, Antonella Paladini, Jo Ann LeQuang, Kailyn Mitchell, Flaminia Coluzzi

Research output: Contribution to journalReview articlepeer-review


Introduction: The definition of nociplastic pain in 2016 has changed the way maladaptive chronic pain is viewed in that it may emerge without neural lesions or neural disease. Many endogenous and pharmacologic substances are being investigated for their role in treating the pain associated with neuronal plasticity. Areas Covered: The authors review promising pharmacologic agents for the treatment of pain associated with maladaptive neuronal plasticity. The authors then provide the reader with their expert opinion and provide their perspectives for the future. Expert opinion: An imbalance between the amplification of ascending pain signals and the poor activation of descending inhibitory signals may be at the root of many chronic pain syndromes. The inhibitory activity of noradrenaline reuptake may play a role in neuropathic and nociplastic analgesia. A better understanding of the brain’s pain matrix, its signaling cascades, and the complex bidirectional communication between the immune system and the nervous system may help meet the urgent and unmet medical need for safe, effective chronic pain treatment, particularly for pain with a neuropathic and/or nociplastic component.

Original languageEnglish (US)
Pages (from-to)105-116
Number of pages12
JournalExpert opinion on pharmacotherapy
Issue number1
StatePublished - 2022


  • maladaptive pain
  • microglial activation
  • neuropathic pain
  • neuroplasticity
  • nociplastic pain
  • pain matrix

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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