Impaired Lymphatic Drainage and Interstitial Inflammatory Stasis in Chronic Musculoskeletal and Idiopathic Pain Syndromes: Exploring a Novel Mechanism

Abstract

A normal functioning lymphatic pump mechanism and unimpaired venous drainage are required for the body to remove inflammatory mediators from the extracellular compartment. Impaired vascular perfusion and/or lymphatic drainage may result in the accumulation of inflammatory substances in the interstitium, creating continuous nociceptor activation and related pathophysiological states including central sensitization and neuroinflammation. We hypothesize that following trauma and/or immune responses, inflammatory mediators may become entrapped in the recently discovered interstitial, pre-lymphatic pathways and/or initial lymphatic vessels. The ensuing interstitial inflammatory stasis is a pathophysiological state, created by specific pro-inflammatory cytokine secretion including tumor necrosis factor alpha, interleukin 6, and interleukin 1b. These cytokines can disable the local lymphatic pump mechanism, impair vascular perfusion via sympathetic activation and, following transforming growth factor beta 1 expression, may lead to additional stasis through direct fascial compression of pre-lymphatic pathways. These mechanisms, when combined with other known pathophysiological processes, enable us to describe a persistent feed-forward loop capable of creating and maintaining chronic pain syndromes. The potential for concomitant visceral and/or vascular dysfunction, initiated and maintained by the same feed-forward inflammatory mechanism, is also described.

One year follow-up on a randomized study investigating serratus anterior muscle and pectoral nerves type I block to reduced neuropathic pain descriptors after mastectomy

“…Chemotherapy and radiation may lead to the development of chronic persistent post-surgical pain 38 . Also, the lymphatic system dysfunction could affect lymph drainage 39 and contribute to chronic pain in general, functional impairment, and depression 40 , 41 . It is important to point that our data did not showed difference between groups in those parameters.…”

“…General anesthesia: patients submitted to general anesthesia only during mastectomy procedure (n = 22 patients). www.nature.com/scientificreports/ dysfunction could affect lymph drainage 39 and contribute to chronic pain in general, functional impairment, and depression 40,41 . It is important to point that our data did not showed difference between groups in those parameters.…”

Temporal model for central sensitization: A hypothesis for mechanism and treatment using systemic manual therapy, a focused review

“…Although important, none of these studies established a cohesive comprehensive theory for CS. Recently we can see attempts to establish such hypotheses for central mechanisms and topography beyond the peripheral morphological changes [52 , 69] . The aim of this review is to further expand on that latter work and create a model that further ties together more of the components thought to be associated with CS.…”

“…Among the methods that can be considered, they either demonstrated these types of effects or are at least hypothesized to do so. These methods include strain counterstrain and fascial counterstrain ( [15 , 68 , 69 , 75] ), Barral visceral and neuro mobilization techniques [1 , 6 , 81] , integrative manual therapy [17 , 73] , craniosacral therapy [53 , 70] , positional release techniques [12 , 61] , and systemic manual therapy (SMT) [24] .…”

The peripheral Epac1/p-Cav-1 pathway underlies the disruption of the vascular endothelial barrier following skin/muscle incision and retraction-induced chronic postsurgical pain

“…Peripheral nerve injuries increase the permeability of the BNB and induce neuropathic pain through the injured afferents ( 14 ). This chronic pain is maintained by continuous neuroinflammation ( 11 , 15 ). After PNS injury, the role of monocytes and macrophages are reported to remain peripheral.…”