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Central Neuropathic Mechanisms in Pain Signaling Pathways: Current Evidence and Recommendations

  • Viswanath, Omar1, 2, 3
  • Urits, Ivan4
  • Burns, James5
  • Charipova, Karina5
  • Gress, Kyle5
  • McNally, Alexandra5
  • Urman, Richard D.6
  • Welschmeyer, Ali5
  • Berger, Amnon A.4
  • Kassem, Hisham7
  • Sanchez, Manuel G.8
  • Kaye, Alan D.9
  • Eubanks, Treniece N.9
  • Cornett, Elyse M.9
  • Ngo, Anh L.8, 4
  • 1 Valley Anesthesiology and Pain Consultants–Envision Physician Services, Phoenix, AZ USA
  • 2 University of Arizona College of Medicine Phoenix,
  • 3 Creighton University School of Medicine,
  • 4 Harvard Medical School,
  • 5 Georgetown University School of Medicine,
  • 6 Brigham and Women’s Hospital,
  • 7 Mount Sinai Medical Center,
  • 8 Department of Pain Medicine, Pain Specialty Group, Newington, NH USA
  • 9 Louisiana State University Health Shreveport,
Published Article
Advances in Therapy
Springer Healthcare
Publication Date
Apr 10, 2020
DOI: 10.1007/s12325-020-01334-w
PMID: 32291648
PMCID: PMC7467462
PubMed Central


Purpose This is a comprehensive review of the current literature on central neuropathic pain mechanisms that is secondary to spinal cord injury. It reviews recent and seminal findings on the pathophysiology, diagnosis, and treatment and compares treatment options and recommendations. Recent Findings Neuropathic pain (NP) is a common complication of spinal cord injury (SCI). Chronicity of NP is attributed to increased abundance of inflammatory mediators and ion channel dysfunction leading to afferent nerve sensitization; nerve damage and nerve–glia cross talk have also been implicated. Conventional treatment is medical and has had limited success. Recent studies have made headway in identifying novel biomarkers, including microRNA and psychosocial attributes that can predict progress from SCI to chronic NP (CNP). Recent advances have provided evidence of efficacy for two promising drugs. Baclofen was able to provide good, long-lasting pain relief. Ziconotide, a voltage-gated calcium channel blocker, was studied in a small trial and was able to provide good analgesia in most participants. However, several participants had to be withdrawn because of worrisome creatine phosphokinase (CPK) elevations, and further studies are required to define its safety profile. Non-medical interventions include brain sensitization and biofeedback techniques. These methods have recently had encouraging results, albeit preliminary. Case reports of non-conventional techniques, such as hypnosis, were also reported. Summary CNP is a common complication of SCI and is a prevalent disorder with significant morbidity and disability. Conventional medical treatment is limited in efficacy. Recent studies identified baclofen and ziconotide as possible new therapies, alongside non-medical interventions. Further research into the pathophysiology is required to identify further therapy candidates. A multidisciplinary approach, including psychosocial support, medical and non-medical interventions, is likely needed to achieve therapeutic effects in this difficult to treat syndrome.

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