The Fascial Continuity–Memory–Reflex Coupling and the Fascial Integration Layer Surrounding the Carotid Sheath with Investing Fascia Involvement: A Hub Hypothesis

This hypothesis proposes, from a holistic perspective, that the human body can be viewed as a tension–sensation–immune integration network grounded in fascial continuity. Systematic reviews have confirmed moderate-strength evidence for intermuscular force transmission along myofascial chains, although evidence for some chains remains insufficient [1]. The central nervous system provides global regulation through procedural motor memory and conditioned reflexes, whereas the peripheral fascia forms mechanical memory and fascial reflexes—defined here as the modulation and amplification of neural reflexes by fascia as a peripheral mechanical–chemical transduction network—through the PIEZO1 and PIEZO2 mechanosensitive channels, axon reflexes, and intrinsic cellular circuits, thereby modulating neural reflex thresholds. The term “reflex coupling” as used here refers specifically to the circuit relationship between central encoding and peripheral fascial modulation, not to two parallel reflex systems.Recent studies have identified CD34+ membranous cells in the subcutaneous fascia that highly express PIEZO and other mechanosensitive genes [2]. Fibroblasts in fascial tissue from a mouse model of arthritis functionally express PIEZO1 and YAP1, and selective ablation of these cells attenuates the therapeutic effects of mechanical stimulation [3]. PIEZO1 and PIEZO2 protein expression has been confirmed in the sensory nerve structures of the human carotid sinus wall [4]. External pressure can be effectively transmitted to carotid sinus tissue with a conduction efficiency of 82%–89% [5]. In human carotid atherosclerotic plaques, Piezo1 expression in myofibroblasts is significantly elevated in symptomatic patients [6], and YAP expression in human carotid plaque tissue correlates with pathological status [7]. Cervical fascial stiffness has been reliably quantified by shear wave elastography (SWE) [8]. The pressure required to reach the deep cervical fascia is approximately 6 N/cm², and the cervical pressure pain threshold is significantly lower than that in the thoracolumbar region [9]. The shear modulus of target fascia is significantly reduced in the stretched position after fascial hydrorelease (FHR) [10]; FHR clinical efficacy has been supported by randomized controlled trials (RCTs) [11,12], and 12-month follow-up has confirmed long-term efficacy [13]. However, the 2026 Chinese expert consensus notes that this technique still lacks the highest level of evidence, and its analgesic mechanism remains incompletely established [14].At the molecular level, YAP has been directly confirmed in human deep fascia [15]. Multiple pathways—including Ang II–AT1R–YAP [16], PIEZO1–YAP [17], PIEZO1–ET-1–HIF-1α–TGF-β [18], and hydrostatic pressure–PIEZO1–YAP1–GLS1 (in rat bladder fibroblasts) [19]—are implicated in fibroblast activation. The functional necessity of the PIEZO1–YAP/TAZ axis for in vivo fibrosis has been verified by conditional gene knockout [20], and Wen et al. systematically reviewed the mechanisms and therapeutic prospects of this axis [21]. A recent study confirmed in human keloid fibroblasts that Piezo1 transfers mechanical signals to YAP via calcium flux to drive matrix production [22]; however, this evidence comes from keloid skin fibroblasts, not fascial tissue. Another study provided direct evidence in human dermal fibroblasts that mechanical stretch induces chromatin accessibility changes and H3K9me3 downregulation [23]; however, this evidence also comes from skin fibroblasts, not fascial fibroblasts. Traditional anatomical descriptions of the “investing fascia as a continuous fibrous layer surrounding the neck” have been challenged. The investing fascia does not exist in the anterior cervical triangle [24], nor between the sternocleidomastoid and trapezius muscles [25]; however, it does exist on the surface of the trapezius, and Diwan et al. confirmed its dense bilaminar structure [26]. A recent developmental histological study further confirmed a three-layered fascial architecture at the carotid sheath level [27]; this evidence comes from a rabbit model and cannot be directly equated with the human fascia surrounding the carotid sheath. This hypothesis therefore adopts the functional term “fascial integration layer surrounding the carotid sheath,” whose anatomical boundaries remain controversial.The core proposition is that central encoding is the primary component, peripheral fascia is the mechanical memory substrate and reflex modulator, and the fascial integration layer surrounding the carotid sheath may be a candidate strategic hub coupling the systemic fascial network with vital organs. This hypothesis has clear falsifiability. Its minimal falsifiable unit is the co-expression of PIEZO1/2 and YAP in resident cells of the human fascia surrounding the carotid sheath. The first-priority validation step is P1, namely directly confirming PIEZO1, PIEZO2, and YAP expression in these cells. If P1 is not confirmed, the direct molecular basis for the fascial resident cell component of this mechanism would be lacking, although PIEZO1/2 expression from other cellular sources might still partially support the pathway. The hypothesis further predicts that if P1 is not confirmed, FHR effects will not correlate with fascial PIEZO1/2 expression and that YAP-dependent fibrotic markers will be absent in fascial resident cells.