Additionally, the theory dealt explicitly with the apparent paradox between the paucity of sensory neurons that responded selectively to intense stimuli and the well-established finding that stimulation of the small fibers in peripheral nerves was required for a sensation to be described as painful.
Is Pain an Immune Response?
Fast forward another 50 years to the adoption of brain imaging techniques, such as functional magnetic resonance imaging (fMRI), as a way to elucidate the maze of pain pathways in the brain. What have we learned from these studies? By analyzing cerebral responses to experimental pain via fMRI, researchers have demonstrated a pain matrix of brain activation, which can be split into medial and lateral pain pathways.5
The medial pain pathway, incorporating the medial nucleus of the thalamus and projecting to the anterior insula and cingulate cortex, processes the cognitive, affective and response aspects of pain, such as learning, prediction, avoidance, attention and anticipation.
In contrast, the lateral pain pathway, comprising the primary and secondary somatosensory cortices, parietal operculum and posterior insula, is predominantly involved in the sensory and discriminative aspects of pain processing, including intensity localization, duration, and temporal and spatial discrimination.
Certainly, functional imaging has helped expose the inner workings of the brain in processing pain. For many clinicians, this might be an engaging topic—but only up to a point. It is in our nature as rheumatologists to try to link clinical symptoms to any potential immunologic underpinnings. Does a link exist between chronic pain and inflammation? Mounting evidence suggests one does. The concept of neuroinflammation—the term used to describe the interaction between brain cells and cytokines—has become a hot topic (see “Can Systemic Inflammation Influence Mood?” The Rheumatologist, August 2015).
A few studies relevant to this field are worth highlighting. The first is an intriguing investigation that asked whether systemic inhibition of TNFα could positively influence central pain processing even before it affects joint inflammation in RA.6 In this small study, fMRI of the brain was able to predict the therapeutic success of TNF inhibition at a very early stage in the course of treatment. As early as 24 hours following a single infusion of infliximab, nociceptive activity in the brain pain matrix was significantly reduced and remained low until the end of the observation period six weeks later. Importantly, this was true even before clinically measurable changes in objective disease symptoms could be recorded or structural effects on the joint, such as a reduction of synovitis on magnetic resonance imaging (MRI), could be detected.
