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THE NEUROIMMUNE SYSTEM In inflammation, the nervous and immune systems work together. Tissue injury or irritation triggers the release of pro-inflammatory molecules into the surrounding interstitial environment (Image 1). Very quickly, the resulting "inflammatory soup" chemically excites and sensitizes nearby peripheral nerves, triggering behavior-altering soreness and pain (as well as initiating the cascade of the inflammatory progression, discussed in "Understanding Inflammation's Progression"). Pain sensitization is a key link between the immune and nervous systems: sensitization amplifies the actual nociceptive signals (not just the experience of pain), either peripherally at the tissue receptors themselves, or centrally, within the spinal cord and brain. Interestingly, inflammation-related sensitization isn't limited to the directly injured areas. Inflammatory markers have also been found within related dorsal root ganglia along the spine (associated with processing chronic pain), neural pathways within the spinal cord, and perhaps most intriguingly, even in immune cells in parts of the brain associated with both sensation and movement of the painful area (glial cells in the sensorimotor cortex, Image 2). 2 In the short term, this neural co- inflammation protectively inhibits muscular activity related to a painful (and potentially injured) area. But if prolonged, inflammatory sensitization can lead to numerous neurological and myofascial changes, including muscle size reduction (within days), reduced fatigue resistance, contraction speed change, and infiltration of fibrous and fatty tissues (within weeks or months, Image 3). Curiously, these inflammatory changes have been observed in muscles and fascia far from an injury, such as in spinal multifidus not adjacent to the site of a disk injury. 3 In other words, inflammation doesn't just affect the fascia and connective tissues of the locally painful area. Over time, local pain can also inflame: • Other myofascial structures far from the injury site; • The neurons that connect the injured areas with the brain; • And strangely, the ankle area of your brain's body map. As bad as this sounds, the body and brain have a tremendous capacity for adaptation. This means that all these things can also get better, and hands-on work has repeatedly been shown to help. 4 There is a lot more to say about hands- on work's relevance to the inflammation/ pain relationship before we get into actual techniques. Other important concepts include the ways local pain and inflammation are affected by systemic (whole-body) inflammation, the role of the vagus nerve and autonomics, stress, the controversies around ice, diet, and much more. For now, you can learn more about these topics in the "Working with Inflammation" webinar (available in ABMP's member library (www.abmp.com/members/ continuing-education/online-learning/ courses/webinar-working-inflammation, or via my website). In future editions of this column, I look forward to describing the specific ways that hands-on approaches can help with both inflammation and pain. Tissue injury releases inflammatory molecules and cells into the surrounding interstitial environment. The resulting "inflammatory soup" chemically excites and sensitizes nearby sensory nerves, generating a nociceptive (pain-triggering) signal. Adapted from Donaldson 2009; image courtesy Advanced-Trainings.com. Over time, inflammation and pain can cause myofascial infiltration of fibrous and fatty tissues. A: Healthy skeletal muscle (rat tibialis anterior) with ~5 percent extracellular material. B: Fibrotic changes six months after inflammatory injury, showing extracellular increase to 20 percent of cross section. In another recent study (Bove et al., 2018), rats with repetitive strain injuries receiving modeled manual therapy (bilateral mobilization, skin rolling, and stretching) showed a reduction in nociceptor activity, neural inflammation, and fibrosis compared to unmassaged rats. Image from Lieber et al., 2013, used under license from The American Physiological Society to Advanced-Trainings.com. 2 3 Yo u r M & B i s w o r t h 2 C E s ! G o t o w w w. a b m p . c o m / c e t o l e a r n m o r e . 101