At low doses, naltrexone (LDN) has been shown to modulate inflammation through the interruption of microglial cell activation within the central nervous system. One of the most likely contributors to centralized pain is changes in microglial cell processing, therefore, it has been postulated that LDN can be used to manage patients with pain resulting from central sensitization due to this relationship. This scoping review aims to synthesize the relevant study data for LDN as a novel treatment strategy for various centralized pain conditions.
A comprehensive literature search was conducted using PubMed, Embase, and Google Scholar guided by the Scale for Assessment of Narrative Review Articles (SANRA) criteria.
47 studies related to centralized pain conditions were identified. Many of the studies were case reports/series and narrative reviews, however a few RCTs have been conducted. Overall, the body of evidence revealed improvement in patient-reported pain severity as well outcomes related to hyperalgesia, physical function, quality of life, and sleep. Variability in dosing paradigms and the time to patient response was present in the reviewed studies.
Evidence synthesized for this scoping review supports the ongoing use of LDN for the treatment of refractory pain in various centralized chronic pain conditions. Upon review of the current available published studies, it is apparent that further high-quality, well-powered RCTs need to be conducted in order to establish efficacy, standardization for dosing, and determine response times. In summary, LDN continues to offer promising results in the management of pain and other distressing symptoms in patients with chronic centralized pain conditions.

© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.