Abstract
Chronic pain is a debilitating condition that still is challenging both clinicians and researchers. Despite intense research, it is still not clear why some individuals develop chronic pain while others do not or how to heal this disease. In this review, we argue for a multisystem approach to understand chronic pain. Pain is not only to be viewed simply as a result of aberrant neuronal activity but also as a result of adverse early-life experiences that impact an individual’s endocrine, immune, and nervous systems and changes which in turn program the pain system. First, we give an overview of the ontogeny of the central nervous system, endocrine, and immune systems and their windows of vulnerability. Thereafter, we summarize human and animal findings from our laboratories and others that point to an important role of the endocrine and immune systems in modulating pain sensitivity. Taking “early-life history” into account, together with the past and current immunological and endocrine status of chronic pain patients, is a necessary step to understand chronic pain pathophysiology and assist clinicians in tailoring the best therapeutic approach.
Highlights
The pain system is modulated by neuroimmune and neuroendocrine mechanisms from embryonic development throughout life
We explore some of the biological mechanisms that may form the foundations of the complexity seen in clinical pain
This review focuses on some of the mechanisms involved in the maturation of the nervous system, which define the function of the pain system later in life
Summary
The pain system is modulated by neuroimmune and neuroendocrine mechanisms from embryonic development throughout life. This altered peripheral endocrine response was accompanied by central neuroendocrine changes, as indicated by increased CRH mRNA levels in the PVN and decreased GR density in the hypothalamus, hippocampus, and frontal cortex following exposure to stress in adulthood [95] These structures are known to mediate the inhibitory effects of glucocorticoids on CRH synthesis in the PVN and the release of ACTH following stress [160, 161], suggesting a decreased negative feedback sensitivity to glucocorticoids and, an enhanced HPA responsiveness to stress following a neonatal immune challenge. New therapeutic approaches, which target neural activity and the neuroendocrine axis, are needed to treat chronic pain patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
