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

Brian Tuckey, John Srbely, Grant Rigney, Meena Vythilingam, Jay Shah, Brian Tuckey, John Srbely, Grant Rigney, Meena Vythilingam, Jay Shah

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.

Keywords: counterstrain techniques; cytokines; fascia; idiopathic diseases; interstitial inflammatory stasis; lymphatic dysfunction; myofascial pain and dysfunction.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Tuckey, Srbely, Rigney, Vythilingam and Shah.

Figures

Figure 1
Figure 1
Trauma and/ or immune responses lead to PC production, most notably IL-1β, IL-6 and TNF-α. PANs of multiple tissues embedded in the ECM are stimulated, transporting these substances to the DRG and DH where glial cells are stimulated leading to central and peripheral neuroinflammation/sensitization. Nociceptive bombardment stimulates somato/visceral-sympathetic reflexes causing the release of NE, resulting in peripheral vasoconstriction (including fascial vasculature) while the cytokines IL-1β, IL-6, TNF-α which deactivate the local lymphatic pump mechanism and simultaneously stimulate fibroblasts to differentiate into myofibroblasts. TGF-b1 released by fibroblasts & myofibroblasts, causes contraction of fascial tissues compressing pre-lymphatic pathways. Impaired hemodynamics from vasoconstriction, deactivation of the lymphatic pump mechanism and compression of pre-lymphatic pathways create areas of hypoxia and IIS. Continued PAN stimulation results in a pathophysiological feed-forward loop of lymphatic stasis, nociceptor stimulation and sympathetic activation which manifests in chronic pain, sub-threshold action potentials and idiopathic visceral/vascular dysfunction.
Figure 2
Figure 2
Nociceptive bombardment (various sources) produces PCs including IL-1β, IL-6, TNF-α etc. PANs of multiple tissues embedded in the ECM are stimulated, transporting these substances to the DRG, causing antidromic release of neuropeptides from the DRG into the injured and neurosegmentally linked tissues, exacerbating the response beyond the region of primary hyperalgesia. Glial cells in the DH are stimulated leading to central and peripheral neuroinflammation/sensitization. PAN entry into the DH at multiple levels alters the activity of alpha and gamma motor neurons, creating multi-segmental muscle guarding reflexes, and myofascial compression of pre-lymphatic pathways. Simultaneously, somato/visceral-sympathetic reflexes are stimulated, causing the release of NE, resulting in peripheral vasoconstriction (including fascial vasculature) while cytokines IL-1β, IL-6, TNF-α deactivate local lymphatic propulsion and stimulate fibroblasts to differentiate into myofibroblasts. TGF-b1 released by fibroblasts & myofibroblasts, creates local fascial contraction, perimysial stiffness (gamma motor activation) and compression of pre-lymphatic pathways. Due to the combined mechanisms, areas of hypoxia and inflammatory stasis develop which continuously stimulate local PANs. A pathophysiological feed-forward loop of lymphatic stasis, nociceptor stimulation and SNA manifests in chronic pain, sub-threshold action potentials and idiopathic visceral/vascular dysfunction.

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