Molecular Aspects of Regional Pain Syndrome: Pain Research and Management

M. Baronio, H. Sadia, S. Paolacci, D. Prestamburgo, D. Miotti, V.A. Guardamagna, G. Natalini, S.G.B. Sullivan, M. Bertelli

Research output: Contribution to journalArticlepeer-review


The purpose of this review is to summarize the pathophysiology of complex regional pain syndrome (CRPS), the underlying molecular mechanisms, and potential treatment options for its management. CRPS is a multifactorial pain condition. CRPS is characterized by prolonged or excessive pain and changes in skin color and temperature, and/or swelling in the affected area, and is generally caused by stimuli that lead to tissue damage. An inflammatory response involving various cytokines and autoantibodies is generated in response to acute trauma/stress. Chronic phase pathophysiology is more complex, involving the central and peripheral nervous systems. Various genetic factors involved in the chronicity of pain have been identified in CRPS patients. As with other diseases of complex pathology, CRPS is difficult to treat and no single treatment regimen is the same for two patients. Stimulation of the vagus nerve is a promising technique being tested for different gastrointestinal and inflammatory diseases. CRPS is more frequent in individuals of 61-70 years of age with a female to male ratio of 3: 1. Menopause, migraine, osteoporosis, and asthma all represent risk factors for CRPS and in smokers the prognosis appears to be more severe. The pathophysiological mechanisms underlying CRPS involve both inflammatory and neurological pathways. Understanding the molecular basis of CRPS is important for its diagnosis, management, and treatment. For instance, vagal nerve stimulation might have the potential for treating CRPS through the cholinergic anti-inflammatory pathway. © 2020 Manuela Baronio et al.
Original languageEnglish
JournalPain Res. Manage.
Publication statusPublished - 2020


  • alendronic acid
  • anesthetic agent
  • anticonvulsive agent
  • antidepressant agent
  • antihypertensive agent
  • autoantibody
  • bisphosphonic acid derivative
  • botulinum toxin
  • calcitonin
  • clodronic acid
  • corticosteroid
  • neridronic acid
  • nonsteroid antiinflammatory agent
  • pamidronic acid
  • asthma
  • biological phenomena and functions concerning the entire organism
  • central nervous system
  • chronic pain
  • chronicity
  • complex regional pain syndrome
  • gastrointestinal disease
  • groups by age
  • heredity
  • human
  • inflammation
  • menopause
  • migraine
  • monogenic disorder
  • osteoporosis
  • pathophysiology
  • peripheral nervous system
  • prognosis
  • Review
  • risk factor
  • skin color
  • skin temperature
  • smoking
  • spinal cord stimulation
  • stress
  • swelling
  • sympathectomy
  • tissue injury
  • vagus nerve stimulation
  • aged
  • female
  • genetics
  • male
  • middle aged
  • Aged
  • Complex Regional Pain Syndromes
  • Female
  • Humans
  • Male
  • Middle Aged


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