1. 2019;22;433-445Updated Review and Treatment Recommendations on Paraneoplastic Neurologic Syndromes and Chronic Pain
   Narrative Review
   Inna Blyakhman, MSc, and Krishnan Chakravarthy, MD, PhD.

BACKGROUND: This comprehensive review of pain in paraneoplastic neurological syndromes focuses on current mechanisms that lead to pain, including autoimmune processes as well as the systemic secretion of factors that sensitize nociceptive nerves. Systemic secretion of functional molecules is a well-recognized phenomenon in endocrine paraneoplastic syndromes; however, cancer pain research has predominantly focused on cytokine-nerve interactions in the tumor microenvironment, and few groups have applied the molecular mechanisms of local pain to study widespread neuropathic pain resulting from systemic secretion. We present a novel perspective in the field of pain research by converging data from clinical oncology with recent molecular pain research on cytokine-mediated sensitization of nociceptive nerves.

OBJECTIVE: Our objective was to conduct a review of paraneoplastic neurological syndromes and provide updates on therapeutic recommendations.

STUDY DESIGN: We used a narrative review design.

METHODS: This review was done using searches of PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles from inception to the present date. Other data sources included hand searches of publications driven by manuscript authors. Search terms included concepts of paraneoplastic syndrome and chronic pain with emphasis on both preclinical and clinical studies.

RESULTS: Articles were screened by title, abstract, and full article review. They were then analyzed by specific clinical indications and appropriate data was presented based on critical analysis of those articles.

LIMITATIONS: More studies that distinguish autoimmune paraneoplastic pain syndromes from those related to systemic cytokine secretion are required.

CONCLUSION: By providing a unified review across disciplines, we illustrate that neuropathic pain related to the systemic secretion of cytokines may represent another category of paraneoplastic neurological syndromes distinct from the well-known autoimmune neuronopathies. In addition, we discuss the clinical significance of distinguishing autoimmune paraneoplastic pain syndromes from those related to systemic cytokine secretion and highlight the need for further research at the intersection of these fields. This review takes a look at both past and current literature with a critical analysis of findings and respective recommendations. In addition, based on review of the literature we provide updated therapeutic recommendations for the consideration of pain practitioners when dealing with this patient population.

KEY WORDS: Paraneoplastic neurologic syndromes, chronic pain, neuropathic pain, treatment guidelines, cytokines