Treatment of central sensitization in patients with 'unexplained' chronic pain: an update

Expert Opin Pharmacother. 2014 Aug;15(12):1671-83. doi: 10.1517/14656566.2014.925446. Epub 2014 Jun 15.


Introduction: Central sensitization (CS) is present in a variety of chronic pain disorders, including whiplash, temporomandibular disorders, low back pain, osteoarthritis, fibromyalgia, headache, lateral epicondylalgia among others. In spite of our increased understanding of the mechanisms involved in CS pain, its treatment remains a challenging issue.

Areas covered: An overview of the treatment options we have for desensitising the CNS in patients with CS pain is provided. These include strategies for eliminating peripheral sources of nociception, as well as pharmacotherapy and conservative interventions that primarily address top-down (i.e., brain-orchestrated) mechanisms.

Expert opinion: A combination of different strategies, each targeting a different 'desensitizing' mechanism, might prove superior over monotherapies. Such combined therapy may include both bottom-up and top-down (e.g., opioids, combined μ-opioid receptor agonist and noradrenaline reuptake inhibitor drugs) strategies. Topically applied analgesic therapies have strong potential for (temporally) decreasing peripheral nociceptive input (bottom-up approach). Targeting metabolic (e.g., ketogenic diets) and neurotrophic factors (e.g., decreasing brain-derived neurotrophic factor) are promising new avenues for diminishing hyperexcitability of the CNS in central sensitization pain patients. Addressing conservative treatments, pain neuroscience education, cognitive behavioural therapy and exercise therapy are promising treatments for CS pain.

Keywords: chronic pain; cognitive behavioural therapy; education; exercise therapy; fibromyalgia; osteoarthritis; pharmacotherapy; rehabilitation; whiplash.

Publication types

  • Review

MeSH terms

  • Analgesics / therapeutic use*
  • Analgesics, Opioid / therapeutic use
  • Animals
  • Central Nervous System Sensitization / drug effects*
  • Chronic Pain / complications*
  • Chronic Pain / drug therapy
  • Chronic Pain / etiology
  • Chronic Pain / therapy*
  • Cognitive Behavioral Therapy
  • Exercise Therapy
  • Humans


  • Analgesics
  • Analgesics, Opioid