Mechanical needling and sterile water hydrodissection modulate nociception via extracellular matrix perturbation and ion channels

Abstract

Background:

Musculoskeletal disorders are increasingly recognized as conditions involving extracellular matrix dysregulation, characterized by fibrosis, calcification, fascial adhesions, and altered nociceptor signaling. These features highlight the role of mechanobiology in pain generation and modulation. Ultrasound-guided hydrodissection has emerged as an intervention capable of perturbing the extracellular microenvironment, with potential downstream effects on nociceptive pathways.

Methods:

A structured literature search was conducted across PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library (January 2000–March 2026) to identify clinical and mechanistic studies investigating ultrasound-guided hydrodissection, mechanical needling, and sterile water injection. Eligible studies were synthesized qualitatively.

Results:

Thirty studies were included, encompassing randomized trials, observational studies, and mechanistic investigations across multiple pain conditions. Evidence suggests that mechanical and osmotic perturbation of the extracellular matrix may disrupt fibrotic architecture, facilitate fascial plane separation, and modify the local biochemical microenvironment. Hypotonic sterile water has been associated with activation of mechanosensitive and osmosensitive ion channels, including TRPV1, PIEZO1/2, and ASIC, leading to calcium influx–mediated modulation of neuronal excitability. These processes may contribute to peripheral and central nociceptive modulation through integrated mechanobiological and microvascular mechanisms.

Conclusions:

Ultrasound-guided mechanical needling with sterile water hydrodissection represents a mechanobiological approach to modulating nociceptive signaling through extracellular matrix perturbation and ion channel activation. This framework provides a translational basis for targeting structural and microenvironmental contributors to pain.

Graphical Abstract

Keywords

Mechanobiology extracellular matrix hydrodissection mechanotransduction TRPV1 PIEZO channels ASIC channels nociception

Introduction

Musculoskeletal disorders are a leading cause of years lived with disability worldwide, substantially impairing mobility, functional independence, and quality of life while imposing a significant socioeconomic burden.^1–3 This burden continues to rise with population aging, sedentary lifestyles, and increasing metabolic and degenerative conditions.

Contemporary pain science has evolved from a predominantly inflammatory paradigm toward a mechanobiological framework, in which structural, cellular, and neurophysiological processes interact dynamically.^4,5 Within this framework, the extracellular matrix functions as an active regulator of tissue mechanics and cellular signaling. Disruption of extracellular matrix homeostasis contributes to pathological remodeling, including fibrosis and calcification, leading to increased tissue stiffness, impaired fascial gliding, and persistent nociceptive input.^6,7

Fibrosis, characterized by excessive extracellular matrix deposition and dysregulated tissue repair, alters tissue elasticity and load distribution, while calcification further reduces compliance and may mechanically irritate adjacent neural and soft tissue structures.^7,8 In addition, altered fascial structure and reduced tissue glide have been associated with chronic pain, reflecting a close interaction between connective tissue and the nervous system.^5,9

At the cellular level, mechanotransduction provides the biological interface linking mechanical stimuli to cellular responses. Cells function as integrated mechanical systems capable of transmitting forces across cytoskeletal and extracellular networks, enabling the conversion of mechanical inputs into biochemical signaling.¹⁰ Mechanosensitive ion channels, including TRPV1 and PIEZO, play key roles in mediating responses to mechanical and osmotic stimuli, contributing to neuronal excitability and peripheral sensitization.^11,12

Despite these advances, current management remains largely pharmacological. Long term use of non steroidal anti inflammatory drugs is associated with significant adverse effects,¹³ while opioids provide limited sustained benefit and carry risks of dependence and adverse outcomes.¹⁴ Clinical guidelines increasingly emphasize non pharmacological and rehabilitation based approaches, although implementation remains inconsistent.¹⁵

Accordingly, there is a growing need for targeted, image guided, and drug sparing interventions that address both structural and neurophysiological drivers of pain. Ultrasound guided mechanical needling combined with hydrodissection represents a promising approach, integrating mechanical modulation of pathological tissue alterations with mechanobiological mechanisms of pain modulation.¹⁶

This narrative review synthesizes current clinical and mechanistic evidence and proposes a clinically applicable mechanobiological framework for ultrasound guided mechanical needling and hydrodissection in the management of chronic musculoskeletal pain.

Literature search strategy

This review integrates relevant clinical and mechanistic evidence on ultrasound guided mechanical needling, hydrodissection techniques, and sterile water injection in the management of musculoskeletal pain.

A structured literature search was conducted across major electronic databases, including PubMed MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library, covering publications from January 2000 to March 2026. Additional studies were identified through Google Scholar and manual screening of reference lists to ensure inclusion of recent and clinically relevant evidence.

Search terms included procedural keywords such as ultrasound guided injection, mechanical needling, hydrodissection, and sterile water injection, combined with condition specific terms including musculoskeletal pain, myofascial pain, lumbar spinal stenosis, and facet joint syndrome. Mechanistic terms included fibrosis, fascia, mechanotransduction, and mechanosensitive ion channels such as TRPV1 and PIEZO.

Both clinical studies, including randomized controlled trials, cohort studies, and observational investigations, and mechanistic or translational studies were included to provide a comprehensive understanding of biological mechanisms and therapeutic effects. Studies lacking clear clinical or mechanistic relevance, or available only as conference abstracts, were excluded.

Given the heterogeneity in study design, patient populations, and intervention protocols, findings were synthesized narratively, with emphasis on integrating clinical outcomes with mechanistic insights to support a coherent and clinically applicable mechanobiological framework.

Overview of evidence

This review identified a focused body of 30 studies examining ultrasound guided hydrodissection, mechanical needling, and sterile water injection in the management of musculoskeletal pain (Figure 1).

Figure 1.

PRISMA flow diagram of the literature search and study selection process.

The majority of clinical evidence relates to ultrasound guided hydrodissection applied in peripheral nerve entrapment syndromes and myofascial pain conditions. Across randomized controlled trials and observational studies, consistent reductions in pain and improvements in functional outcomes have been reported, primarily attributed to mechanical separation of fibrotic tissue planes and restoration of neural mobility.^17–29

Hydrodissection using isotonic saline or dextrose solutions reduces mechanical compression on peripheral nerves and improves fascial gliding, thereby facilitating restoration of biomechanical function.^17–29 These structural effects are supported by mechanistic and translational evidence demonstrating that disruption of connective tissue adhesions and restoration of tissue mobility contribute to reduced nociceptive input and functional improvement.^17–29

At the molecular and experimental level, mechanosensitive responses to mechanical and fluid mediated stimuli provide a biologically plausible basis for therapeutic effects. Experimental and translational studies indicate that tissue deformation and fluid interface modulation contribute to neuromodulation and altered nociceptive signaling.^30–36

Evidence specific to sterile water injection demonstrates consistent analgesic effects across multiple randomized controlled trials and clinical pain models, supporting a mechanism involving transient nociceptive activation followed by engagement of endogenous inhibitory pathways, consistent with conditioned pain modulation.^30–36

Direct comparative evidence remains limited, particularly in distinguishing the relative contributions of mechanical versus injectate-specific effects. However, randomized controlled trials in intra-articular interventions demonstrate that saline injection, often considered inert, may produce clinically meaningful improvements, supporting a role for mechanical distension and local tissue effects independent of pharmacological action.^29,37–40

Taken together, the therapeutic effects of ultrasound guided mechanical needling and hydrodissection appear to arise from a multimodal interaction involving mechanical tissue release, neuromodulation, and restoration of microenvironmental function, including improved tissue mobility and local physiological conditions.^{17–29,30–36}

However, the current evidence base remains heterogeneous, with variability in procedural techniques, injectate selection, and outcome measures.

Overall, the available evidence supports the biological plausibility and emerging clinical relevance of ultrasound guided mechanical needling combined with sterile water hydrodissection as a structurally targeted and mechanism informed intervention for chronic musculoskeletal pain.^41–46

Additional evidence from clinical pain models further supports the neuromodulatory mechanism of sterile water injection, demonstrating transient nociceptive activation followed by engagement of endogenous inhibitory pathways consistent with conditioned pain modulation.^{30–36,47–49}

A summary of representative clinical and mechanistic studies is provided in Table 1.

Table 1.

Representative clinical and mechanistic studies of ultrasound-guided hydrodissection and sterile water injection in pain management (n = 30 studies).

Domain	Author (ref.)	Design	Condition	Intervention	Injectate	n	Key outcomes	Mechanism	Level
Nerve entrapment	Wu et al.¹⁷	RCT	CTS	Perineural HD	D5W	49	Reduced pain; improved nerve conduction	Mech + Neuro	Level I
Nerve entrapment	Wu et al.¹⁸	RCT	CTS	HD	D5W	44	Reduced symptom severity	Mech	Level I
Nerve entrapment	Wu et al.¹⁹	RCT	CTS	Dextrose vs steroid	D5W vs triamcinolone	54	Comparable or superior outcomes vs steroid	Mech + Neuro	Level I
Nerve entrapment	Tagliafico et al.²⁰	Prospective	Meralgia paresthetica	HD	NS	20	Improved neuropathic symptoms	Mech	Level II
Nerve entrapment	Lin et al.²¹	RCT	CTS	Volume comparison	D5W	63	Higher volume improved outcomes	Mech	Level I
Nerve entrapment	Elawamy et al.²²	RCT	CTS	HD	Hyaluronidase	60	Improved pain and function	Mech	Level I
Nerve entrapment	Su et al.²³	RCT (DB)	CTS	Perineural injection	Hyaluronic acid	40–60	Sustained improvement in pain and function	Mech + Inj-spec	Level I
Nerve entrapment	Salman Roghani et al.²⁴	RCT (TB)	CTS	Dose comparison	Corticosteroid	≈60	Dose-dependent improvement	Inj-spec	Level I
Nerve entrapment	Huang et al.²⁵	RCT	CTS	Volume effect	NS	24	Higher volume improved outcomes	Mech	Level I
Nerve entrapment	Eyvaz et al.²⁶	RCT	CTS	Volume comparison	D5W	60–80	Dose–volume relationship	Mech	Level I
Myofascial pain	Hsu et al.²⁷	RCT	MPS	Interfascial HD	Dextrose	≈60	Reduced pain; improved function	Mech	Level I
Myofascial pain	Wu et al.²⁸	Observational	MPS	Interfascial HD	Dextrose	≈70	Clinical improvement	Mech	Level II
Myofascial pain	Shi et al.²⁹	RCT	Meralgia paresthetica	Dextrose vs steroid	D5W vs steroid	≈56	Superior long-term outcomes	Neuro	Level I
SWI	Gul and Gul³⁰	RCT	Lithotripsy pain	Intracutaneous SWI	SWI	524	Comparable analgesia to NSAIDs; fewer adverse effects	Neuro	Level I
SWI	Louca Jounger et al.³¹	RCT (crossover)	Experimental pain	Intramuscular SWI	SWI	30	Comparable pain response to hypertonic saline	Neuro	Level I
SWI	Tekin et al.³²	RCT	Low back pain	Intradermal SWI	SWI	112	Reduced pain and opioid use	Neuro	Level I
SWI	Haider et al.³³	RCT	Labor pain	Subdermal SWI	SWI	212	Effective analgesia	Neuro	Level I
SWI	Mårtensson et al.³⁴	RCT	Injection pain model	SWI ± topical anesthesia	SWI	120	Reduced procedural pain	Neuro	Level I
SWI	Rezaie et al.³⁵	RCT	Labor pain	SWI vs saline	SWI vs NS	164	Both interventions effective	Mech + Neuro	Level I
SWI	Mozafari et al.³⁶	RCT	Renal colic	SWI vs morphine	SWI	94	Effective alternative analgesia	Neuro	Level I
Mechanical	Nunes-Tamashiro et al.³⁷	RCT	Knee OA	Intra-articular injection	PRP/steroid/NS	100	Clinically meaningful improvement in saline group	Mech + Inj-spec	Level I
Mechanical	Lundsgaard et al.³⁸	RCT	Knee OA	Hyaluronate vs saline	–	251	No significant difference	Mech	Level I
Mechanical	Moosmayer et al.³⁹	RCT	Calcific tendinopathy	Lavage vs sham	–	–	Improved outcomes with mechanical removal	Mech	Level I
Author studies	Chen and Suputtitada⁴¹	Comparative	Lumbar stenosis	Needling + SWI	SWI	≈60	Functional improvement	Comb	Level II
Author studies	Suputtitada et al.⁴²	Clinical	Facet syndrome	US-guided injection	–	≈90	Improved targeting and outcomes	Mech	Level II
Author studies	Suputtitada et al.⁴⁴	Observational	Lumbar stenosis	SWI vs lidocaine	SWI vs lidocaine	>4000	Sustained long-term improvement	Neuro	Level II
Author studies	Suputtitada et al.⁴⁵	Observational	Facet syndrome	SWI vs steroid	SWI vs steroid	>4000	Long-term clinical benefit	Comb	Level II
Labor pain	Mårtensson et al.⁴⁷	RCT	Labor pain	SWI vs acupuncture	SWI	≈100	Comparable analgesic effect	Neuro	Level I
Labor pain	Lee et al.⁴⁸	RCT (multicenter)	Labor pain	SWI	SWI	>1000	Reduced pain without increased cesarean rate	Neuro	Level I
Labor pain	Lee et al.⁴⁹	RCT (DB)	Labor pain	SWI vs placebo	SWI	≈200	Significant analgesic effect	Neuro	Level I

Comb: combined mechanisms; CTS: carpal tunnel syndrome; D5W: 5% dextrose in water; DB: double-blind; HD: hydrodissection; Inj-spec: injectate-specific effect; Mech: mechanical separation or tissue distension; MPS: myofascial pain syndrome; Neuro: neuromodulatory effect; NS: normal saline; OA: osteoarthritis; PRP: platelet-rich plasma; RCT: randomized controlled trial; SWI: sterile water injection; TB: triple-blind.

Sample sizes are reported as exact values where available; approximate values are denoted by (≈), and large datasets by (>).

Discussion

Chronic musculoskeletal pain represents a major global health burden and is increasingly conceptualized as a multiscale disorder involving extracellular matrix (ECM) dysregulation, fibrosis, altered biomechanics, and persistent nociceptive sensitization rather than a purely inflammatory condition.^1–3 The ECM functions as a dynamic mechanosensitive network that regulates force transmission and cellular signaling, and its disruption leads to increased tissue stiffness, impaired fascial gliding, and abnormal load distribution.^4–6 These structural changes are strongly associated with persistent nociceptive input, particularly in conditions such as chronic low back pain, where reduced fascial shear strain and mechanical restriction have been demonstrated.^8,9 These structural abnormalities are directly visualized on clinical imaging (Figures 2 and 3), where calcification and fibrosis at the facet joint contribute to localized mechanical compression and altered load transmission. This imaging–pathology correlation reinforces the role of targeted, ultrasound-guided interventions in addressing both structural and mechanobiological drivers of pain.^4,7,37,53

Figure 2.

Degenerative structural changes of the lumbar spine. Structural alterations, including disc degeneration, osteophyte formation, and narrowing of the neural foramina, contribute to nerve root irritation and persistent musculoskeletal pain.

Figure 3.

Ultrasound-guided needle targeting of the facet joint. Real-time ultrasound imaging demonstrates needle advancement into regions of calcification and fibrosis within the facet joint, enabling precise mechanical needling and hydrodissection.

Mechanotransduction provides the molecular link between structural pathology and pain signaling, whereby mechanical and osmotic stimuli are converted into intracellular biochemical responses.^6,10 Mechanosensitive ion channels, including transient receptor potential vanilloid 1 (TRPV1) and PIEZO1/2, play a central role in this process by mediating cation influx, membrane depolarization, and nociceptor activation.^11,12 These channels operate within an integrated ECM–cytoskeletal system, in which mechanical forces are transmitted across cellular structures, amplifying nociceptive signaling in fibrotic and mechanically restricted tissues.^6,10 In addition, persistent peripheral input may contribute to central sensitization, further sustaining chronic pain states.⁵²

Hydrodissection targets these mechanisms at the structural level by mechanically separating tissue planes, releasing adhesions, and decompressing entrapped neural structures.^16,54 Clinical studies in peripheral nerve entrapment, including carpal tunnel syndrome, demonstrate that hydrodissection can improve symptoms and function, with outcomes influenced by injectate volume and distribution.^{17–19,21–23} Similar benefits have been reported in myofascial pain and meralgia paresthetica, supporting the role of mechanical decompression and restoration of tissue mobility in reducing nociceptive input.^20,27–29 These multilevel effects are systematically summarized in Table 2, which integrates structural, neuromodulatory, and microvascular mechanisms into a unified mechanobiological framework.

Table 2.

Mechanobiological framework of ultrasound-guided mechanical needling with sterile water hydrodissection.

Mechanistic domain	Biological process	Proposed mechanism	Clinical implication	Supporting evidence
	I. Structural–mechanical effects (tissue release and decompression)
Fibrotic tissue disruption	Breakdown of fibrotic adhesions and calcified connective tissue	Mechanical needling fragments fibrotic tissue and microcalcifications, restoring fascial mobility and reducing abnormal mechanical stress	Decreases stiffness and mechanically induced pain; improves tissue flexibility	^4,5,16
Hydrodissection of fascial planes	Separation of adherent tissue layers	Injected fluid expands interfascial space, separating tissue planes, and relieving compression of neurovascular structures	Reduces nerve entrapment and improves range of motion	^{13–15,22–24}
Restoration of neural excursion	Improved nerve gliding	Decompression and separation of surrounding connective tissue restore neural mobility and reduce traction-related nociception	Reduces movement-related pain and enhances functional recovery	^17–21
	II. Neuromodulatory effects (sterile water–mediated mechanotransduction)
Ion channel activation	Activation of mechanosensitive and osmosensitive nociceptors	Hypotonic sterile water activates TRPV1, PIEZO1/2, and ASIC channels, producing transient nociceptive input followed by modulation of peripheral signaling	Rapid analgesia with reduction in peripheral sensitization	^{11,12,16,30,31}
Conditioned pain modulation	Activation of endogenous inhibitory pathways	Transient nociceptive stimulation triggers central pain inhibitory mechanisms (descending modulation)	Sustained analgesic effect beyond local injection	^30–33
Neurosensory adaptation	Peripheral and central desensitization	Repeated mechanosensory input may recalibrate nociceptive processing and reduce hypersensitivity	Improves pain tolerance and functional participation	^{11,12,30–33}
	III. Microvascular and tissue recovery effects
Microvascular reperfusion	Restoration of tissue perfusion and oxygenation	Release of fibrotic constraints and expansion of tissue planes improve local circulation and reduce hypoxia	Reduces ischemia-related pain and supports tissue healing	^4,5,16,27
Metabolic recovery	Improved nutrient exchange	Enhanced perfusion facilitates removal of inflammatory mediators and metabolic waste	Promotes recovery and reduces chronic nociceptive input	^4,5
Connective tissue remodeling	Regulation of fibroblast activity and extracellular matrix turnover	Mechanical stimulation influences mechanotransduction pathways, promoting normalization of collagen organization	Supports long-term structural restoration and reduces recurrence	^4,5,6,16

The choice of injectate further modifies these effects through distinct physicochemical and biological mechanisms. Normal saline, as an isotonic solution, acts primarily through mechanical hydrodissection, increasing interstitial volume and reducing tissue compression.^13–15 Its limited effect on transmembrane ionic gradients suggests minimal direct activation of mechanosensitive ion channels, and its analgesic effects are therefore largely attributable to biomechanical decompression.^13–16 Nevertheless, clinical studies in knee osteoarthritis demonstrate that saline injections can produce meaningful improvements, highlighting the therapeutic importance of mechanical factors such as tissue expansion and pressure modulation.^37,38,43

Dextrose-based injectates (D5W) provide additional biochemical and metabolic modulation beyond mechanical effects. Glucose may influence neuronal metabolism, ATP-dependent ion transport, and inflammatory pathways, contributing to stabilization of membrane excitability and reduction of neurogenic inflammation.^{17–19,21–23} Randomized trials have demonstrated sustained benefits of D5W hydrodissection in carpal tunnel syndrome, with evidence suggesting both mechanical and biochemical contributions.^21,25,26 However, the presence of glucose introduces metabolic and osmotic considerations, particularly in multi-site procedures or in individuals with altered glucose homeostasis, such as diabetes mellitus, where local tissue responses may differ. Importantly, D5W does not create strong osmotic gradients and therefore has limited capacity to directly activate ion channels such as TRPV1 or PIEZO.^11,12

Sterile water represents a mechanistically distinct injectate characterized by its hypotonicity and its ability to induce osmotic-driven cellular responses. The resulting osmotic gradient leads to rapid water influx, transient cellular swelling, and membrane deformation, directly activating mechanosensitive and osmosensitive ion channels, including TRPV1 and PIEZO1/2.^11,12 This activation produces rapid cation influx, particularly calcium, resulting in transient nociceptor excitation followed by desensitization and reduced neuronal excitability. This biphasic response is consistent with conditioned pain modulation, whereby a brief nociceptive stimulus activates endogenous inhibitory pathways and leads to net analgesia.^{30–36,47–49}

Importantly, sterile water exerts integrated effects across multiple tissue compartments within a single intervention. At the neural level, it modulates nociceptive signaling through ion channel activation and reduces peripheral sensitization.^11,12 At the muscular level, mechanical needling combined with fluid injection may disrupt myofascial trigger points and reduce localized hypertonicity. At the fascial level, hydrodissection restores tissue gliding and reduces stiffness, improving force transmission across connective tissue planes.^4–7,9,55 At the joint level, mechanical decompression and modulation of periarticular tissues may reduce intra-articular pressure and improve joint biomechanics, as supported by studies in osteoarthritis and facet joint syndrome.^37,38,53 At the vascular level, decompression of microvascular structures and changes in interstitial pressure may enhance tissue perfusion and oxygenation.^16,54

The vascular component is particularly important in chronic pain states. Microvascular compromise and local ischemia are common in fibrotic tissues, where increased ECM density can compress small vessels and impair perfusion.^4,7,9 Endothelial cells are highly mechanosensitive and respond to shear stress and mechanical forces through pathways involving cytoskeletal–ECM coupling and ion channel activation.^6,10 These processes regulate nitric oxide production, vascular tone, and inflammatory signaling, all of which influence nociceptive sensitivity. Restoration of microvascular dynamics through mechanical decompression and osmotic modulation may therefore contribute to both tissue recovery and pain reduction.^6,10,16

Author-derived studies further support this integrated mechanistic model. Mechanical needling combined with sterile water injection has demonstrated sustained clinical improvement in lumbar spinal stenosis and facet joint syndrome, suggesting that targeting both structural and molecular mechanisms leads to more durable outcomes.^41–45 These findings are consistent with a framework in which simultaneous modulation of neural, muscular, fascial, joint, and vascular components produces synergistic therapeutic effects.

These differences across injectates are summarized in Table 3, highlighting their distinct mechanistic profiles and clinical implications.

Table 3.

Comparison of injectates used in hydrodissection: mechanisms, neuromodulation, and clinical implications.

Injectate	Osmolarity/property	Primary mechanism	Neuromodulation	Advantages	Limitations/considerations	Clinical implication
NSS	Isotonic	Mechanical hydrodissection (fascial separation, nerve decompression)	Minimal	Safe, widely available, no metabolic effect	Limited neuromodulation	Effective for structural decompression and restoration of tissue gliding
D5W	Mildly hypertonic	Mechanical hydrodissection and biochemical modulation	Moderate	May reduce peripheral sensitization; supported in nerve entrapment (e.g. CTS)	Glucose load (caution in diabetes, multiple sites)	Combined mechanical and biochemical analgesic effect
Sterile water	Hypotonic	Mechanical hydrodissection and osmotic stimulation	Strong	Activates mechanosensitive and osmosensitive ion channels including TRPV1, PIEZO1/2, and ASIC; induces conditioned pain modulation; no glucose load; suitable for multi-site injections, no metabolic effect	Transient injection discomfort	Mechanobiological integration (mechanical and neuromodulatory effects); potential for sustained analgesia, reduction of sensitization, and functional recovery

D5W: 5% dextrose; NSS: normal saline.

In contrast, conventional pharmacological therapies such as non-steroidal anti-inflammatory drugs and opioids primarily target downstream inflammatory or central pathways without addressing underlying mechanobiological dysfunction.^13,14 This limitation underscores the need for mechanism-based, drug-sparing interventions that act at the level of tissue structure and mechanotransduction. Clinical guidelines increasingly support non-pharmacological approaches for chronic low back pain, reflecting this shift toward addressing upstream drivers of pain.¹⁵

Despite these advances, several limitations remain. Heterogeneity in study design, injectate composition, and outcome measures limits direct comparison across studies, and most clinical studies lack direct molecular validation. Future research should integrate molecular biomarkers, ion channel activity, and imaging of ECM and fascial dynamics to directly link mechanotransduction with clinical outcomes. Mechanism-driven randomized trials will be essential to clarify the relative contributions of mechanical, biochemical, and osmotic effects.

This approach supports a shift from technique-based to mechanism-based intervention, where injectate selection and procedural strategy are guided by underlying tissue pathology and mechanotransductive signaling rather than a one-size-fits-all approach.

Collectively, these mechanisms provide a biologically coherent link between extracellular matrix perturbation, ion channel activation, and multilevel modulation of nociceptive signaling.

In summary, normal saline, dextrose, and sterile water represent a continuum of injectate mechanisms. Saline acts predominantly through mechanical decompression, dextrose combines mechanical and biochemical modulation, and sterile water uniquely integrates mechanical hydrodissection with osmotic activation of mechanosensitive ion channels. These integrated effects across neural, muscular, fascial, joint, and vascular systems provide a coherent mechanobiological framework for understanding and optimizing injection based therapies in chronic musculoskeletal pain.^{11,12,16–19,21–30,35–45,47–51,54,55}

Conclusion

Ultrasound-guided mechanical needling combined with sterile water hydrodissection represents a mechanobiologically informed approach to musculoskeletal pain, integrating structural intervention with molecular-level neuromodulation. By disrupting fibrotic adhesions, restoring fascial mobility, and inducing osmotic-driven activation of mechanosensitive ion channels such as TRPV1 and PIEZO1/2, this technique targets both the physical and signaling substrates of nociception.

Current evidence supports a model in which mechanical decompression and osmotic stimulation interact to modulate peripheral nociceptive input, potentially influencing downstream central processing. These effects extend beyond analgesia, encompassing restoration of tissue dynamics, normalization of mechanotransductive signaling, and improvement in functional outcomes.

Compared with isotonic and glucose-based injectates, sterile water uniquely provides a hypotonic microenvironment capable of directly engaging ion channel–mediated pathways while preserving the mechanical benefits of hydrodissection. This dual mechanism positions sterile water as a distinct tool within a spectrum of injectate strategies.

Importantly, this framework supports a transition toward mechanism-based intervention, in which procedural and injectate selection are guided by underlying tissue pathology and mechanotransductive processes rather than empirical approaches. Such a strategy aligns with emerging paradigms in precision and regenerative pain medicine.

While further studies are required to directly validate molecular pathways and define optimal protocols, ultrasound-guided mechanical needling with sterile water hydrodissection provides a coherent and biologically plausible model that bridges tissue-level intervention with ion channel–mediated neuromodulation in chronic musculoskeletal pain.

Footnotes

Author contributions

CPCC and AS contributed equally to the drafting, integration, and development of the manuscript, including literature synthesis, data interpretation, and health-systems analysis. AS conceived the study, developed the conceptual and policy framework, led key sections of the manuscript, and provided senior scientific and clinical leadership, including critical revision for important intellectual content. All authors meet the ICMJE authorship criteria and approved the final version of the manuscript.

Consent for publication

Not applicable.

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AS has developed and applied the ultrasound-guided mechanical needling with sterile water injection (SWI) technique described in this manuscript as part of routine clinical practice. AS and CPCC have authored peer-reviewed studies evaluating SWI. The authors declare no other competing interests.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Science and Technology Council of Taiwan (grant numbers NSTC114-2314-B182-021-MY2; NMRPD1Q0921-2).

Institutional review board statement

Not applicable. This study is a structured narrative review based on previously published literature and did not involve human participants, identifiable data, or experimental interventions. Patients and the public were not involved in the design, conduct, or reporting of this research.

Human and animal rights

This article does not contain any studies with human or animal subjects performed by the authors.

ORCID iD

Areerat Suputtitada

References

GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020; 396(10258): 1204–1222. Erratum in: Lancet 2020; 396(10262): 1562.

Safiri

Kolahi

Smith

Hill

Bettampadi

Mansournia

Hoy

Ashrafi-Asgarabad

Sepidarkish

Almasi-Hashiani

Collins

Kaufman

Qorbani

Moradi-Lakeh

Woolf

Guillemin

March

Cross

. Global, regional and national burden of osteoarthritis 1990–2017: a systematic analysis of the Global Burden of Disease Study 2017. Ann Rheum Dis 2020; 79(6): 819–828.

Briggs

Woolf

Dreinhöfer

Homb

Hoy

Kopansky-Giles

Åkesson

, March L. Reducing the global burden of musculoskeletal conditions. Bull World Health Organ 2018; 96(5): 366–368.

Kjaer

. Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev 2004; 84(2): 649–698.

Langevin

Sherman

. Pathophysiological model for chronic low back pain integrating connective tissue and nervous system mechanisms. Med Hypotheses 2007; 68(1): 74–80.

Humphrey

Dufresne

Schwartz

. Mechanotransduction and extracellular matrix homeostasis. Nat Rev Mol Cell Biol 2014; 15(12): 802–812.

Wynn

. Cellular and molecular mechanisms of fibrosis. J Pathol 2008; 214(2): 199–210.

Adams

Roughley

. What is intervertebral disc degeneration, and what causes it?. Spine 2006; 31(18): 2151–2161.

Langevin

Fox

Koptiuch

Badger

Greenan-Naumann

Bouffard

Konofagou

Lee

Triano

Henry

. Reduced thoracolumbar fascia shear strain in human chronic low back pain. BMC Musculoskelet Disord 2011; 12: 203.

10.

Ingber

. Tensegrity-based mechanosensing from macro to micro. Prog Biophys Mol Biol 2008; 97(2–3): 163–179.

11.

Caterina

Schumacher

Tominaga

Rosen

Levine

Julius

. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997; 389(6653): 816–824.

12.

Coste

Mathur

Schmidt

Earley

Ranade

Petrus

Dubin

Patapoutian

. PIEZO1 and PIEZO2 are essential components of distinct mechanically activated cation channels. Science 2010; 330(6000): 55–60.

13.

Coxib and traditional NSAID Trialists’ (CNT) Collaboration; Bhala

Emberson

Merhi

Abramson

Arber

Baron

Bombardier

Cannon

Farkouh

FitzGerald

Goss

Halls

Hawk

Hawkey

Hennekens

Hochberg

Holland

Kearney

Laine

Lanas

Lance

Laupacis

Oates

Patrono

Schnitzer

Solomon

Tugwell

Wilson

Wittes

Baigent

. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382(9894): 769–779.

14.

Busse

Wang

Kamaleldin

Craigie

Riva

Montoya

Mulla

Lopes

Vogel

Chen

Kirmayr

De Oliveira

Olivieri

Kaushal

Chaparro

Oyberman

Agarwal

Couban

Tsoi

Lam

Vandvik

Hsu

Bala

Schandelmaier

Scheidecker

Ebrahim

Ashoorion

Rehman

Hong

Ross

Johnston

Kunz

Sun

Buckley

Sessler

Guyatt

. Opioids for chronic noncancer pain: a systematic review and meta-analysis. JAMA 2018; 320(23): 2448–2460.

15.

Qaseem

Wilt

McLean

Forciea

; Clinical Guidelines Committee of the American College of Physicians; Denberg

Barry

Boyd

Chow

Fitterman

Harris

Humphrey

Vijan

. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2017; 166(7): 514–530.

16.

Lam

KHS

Hung

Chiang

Onishi

DCJ

Clark

Reeves

. Ultrasound-guided nerve hydrodissection for pain management: rationale, methods, current literature, and theoretical mechanisms. J Pain Res 2020; 13: 1957–1968.

17.

Chou

Tsai

Chen

. Six-month efficacy of perineural dextrose for carpal tunnel syndrome: a prospective, randomized, double-blind, controlled trial. Mayo Clin Proc 2017; 92(8): 1179–1189.

18.

Chen

Shen

Tsai

Chen

. Nerve hydrodissection for carpal tunnel syndrome: a prospective, randomized, double-blind, controlled trial. Muscle Nerve 2019; 59(2): 174–180.

19.

Shen

Chen

. Randomized double-blinded clinical trial of 5% dextrose versus triamcinolone injection for carpal tunnel syndrome patients. Ann Neurol 2018; 84(4): 601–610.

20.

Tagliafico

Serafini

Lacelli

Perrone

Valsania

Martinoli

. Ultrasound-guided treatment of meralgia paresthetica (lateral femoral cutaneous neuropathy): technical description and results of treatment in 20 consecutive patients. J Ultrasound Med 2011; 30(10): 1341–1346.

21.

Lin

Liao

Hsiao

Hsueh

Chao

. Volume matters in ultrasound-guided perineural dextrose injection for carpal tunnel syndrome: a randomized, double-blinded, three-arm trial. Front Pharmacol 2020; 11: 625830.

22.

Elawamy

Hassanien

Hamed

Roushdy

ASI

Abass

Mohammed

Hasan

MRAR

Kamel

. Efficacy of hyalase hydrodissection in the treatment of carpal tunnel syndrome: a randomized, double-blind, controlled, clinical trial. Pain Physician 2020; 23(2): E175–E183.

23.

Shen

Chen

. The efficacy of hyaluronic acid for carpal tunnel syndrome: a randomized double-blind clinical trial. Pain Med 2021; 22(11): 2676–2685.

24.

Salman Roghani

Holisaz

Tarkashvand

Delbari

Gohari

Boon

Lokk

. Different doses of steroid injection in elderly patients with carpal tunnel syndrome: a triple-blind, randomized, controlled trial. Clin Interv Aging 2018; 13: 117–124.

25.

Huang

Lai

Reeves

Lam

KHS

Cheng

. Volume effect of nerve hydrodissection for carpal tunnel syndrome: a prospective, randomized, and single-blind study. J Ultrasound Med 2024; 43(1): 161–169.

26.

Eyvaz

Adar

Akçin

Aİ

Dündar

Toktaş

Eroğlu

. Comparison of ultrasound-guided hydrodissection with various volumes of 5% dextrose for carpal tunnel syndrome: a prospective randomized controlled double-blind trial. Am J Phys Med Rehabil 2025; 104(7): 596–604.

27.

Hsu

Lin

Cheng

. Additional effect of interfascial hydrodissection with dextrose on shoulder and neck function in patients with myofascial pain syndrome: a randomized control trial. Am J Phys Med Rehabil 2024; 103(9): 827–834.

28.

Song

Liao

Yang

. Ultrasound-guided 10% dextrose interfascial hydrodissection for patients with myofascial pain syndrome: a retrospective observational study. Medicine 2025; 104(25): e42587.

29.

Shi

Zhu

Bai

. A randomized double-blind trial of 5% dextrose versus corticosteroid hydrodissection for meralgia paresthetica. Pain Physician 2024; 27(8): E835–E842.

30.

Gul

. Intracutaneous sterile water injection for pain relief during extracorporeal shock wave lithotripsy: comparison with diclofenac sodium. Urolithiasis 2020; 48(2): 103–108.

31.

Louca Jounger

Svedenlöf

Elenius

Källkrans

Scheid

Ernberg

Christidis

. Sterile water; a novel and promising human experimental craniofacial muscle pain model. J Oral Rehabil 2021; 48(6): 654–665.

32.

Tekin

Gur

Bayraktar

Ozlu

Celik

. The effectiveness of intradermal sterile water injection for low back pain in the emergency department: a prospective, randomized controlled study. Am J Emerg Med 2021; 42: 103–109.

33.

Haider

Qureshi

Bashir

Aslam

Mushtaq

Masoom

. Use of subdermal sterile water injection torelievepain in labour and its effect in mode of delivery. J Coll Physicians Surg Pak 2026; 36(1): 51–55.

34.

Mårtensson

Gunnarsson

Karlsson

Lee

Bergh

. Effect of topical local anaesthesia on injection pain associated with administration of sterile water injections – a randomized controlled trial. BMC Anesthesiol 2022; 22(1): 35.

35.

Rezaie

Shaabani

Jahromi

Dakhesh

. The effect of subcutaneous and intracutaneous injections of sterile water and normal saline on pain intensity in nulliparous women: a randomized controlled trial. Iran J Nurs Midwifery Res 2019; 24(5): 365–371.

36.

Mozafari

Verki

Tirandaz

Mahjouri

. Comparing intradermal sterile water with intravenous morphine in reducing pain in patients with renal colic: a double-blind randomized clinical trial. Rev Recent Clin Trials 2020; 15(1): 76–82.

37.

Nunes-Tamashiro

Natour

Ramuth

Toffolo

Mendes

Rosenfeld

Furtado

RNV

. Intra-articular injection with platelet-rich plasma compared to triamcinolone hexacetonide or saline solution in knee osteoarthritis: a double blinded randomized controlled trial with one year follow-up. Clin Rehabil 2022; 36(7): 900–915.

38.

Lundsgaard

Dufour

Fallentin

Winkel

Gluud

. Intra-articular sodium hyaluronate 2 mL versus physiological saline 20 mL versus physiological saline 2 mL for painful knee osteoarthritis: a randomized clinical trial. Scand J Rheumatol 2008; 37(2): 142–150.

39.

Moosmayer

Ekeberg

Hallgren

Heier

Kvalheim

Juel

Blomquist

Pripp

Brox

. Ultrasound guided lavage with corticosteroid injection versus sham lavage with and without corticosteroid injection for calcific tendinopathy of shoulder: randomised double blinded multi-arm study. BMJ 2023; 383: e076447.

40.

Hauser

Lackner

Steilen-Matias

Harris

. A systematic review of dextrose prolotherapy for chronic musculoskeletal pain. Clin Med Insights Arthritis Musculoskelet Disord 2016; 9: 139–159.

41.

Chen

CPC

Suputtitada

. Prolotherapy at multifidus muscle versus mechanical needling and sterile water injection in lumbar spinal stenosis. J Pain Res 2023; 16: 2477–2486.

42.

Suputtitada

Chen

Peng

Yen

Chen

CPC

. Determining the most suitable ultrasound-guided injection technique in treating lumbar facet joint syndrome. Biomedicines 2023; 11(12): 3308.

43.

Suputtitada

Nopsopon

Rittiphairoj

Pongpirul

. Intra-articular facet joint injection of normal saline for chronic low back pain: a systematic review and meta-analysis. Medicina 2023; 59(6): 1038.

44.

Suputtitada

Chen

CPC

Pongpirul

. Mechanical needling with sterile water versus lidocaine injection for lumbar spinal stenosis. Global Spine J 2024; 14(1): 82–92.

45.

Suputtitada

Chen

CPC

Pongpirul

. Mechanical needling with sterile water versus steroid injection for facet joint syndrome: a retrospective observational study. Pain Res Manag 2022; 2022: 9830766.

46.

Finnoff

Hall

Adams

Berkoff

Concoff

Dexter

Smith

; American Medical Society for Sports Medicine. American Medical Society for Sports Medicine position statement: interventional musculoskeletal ultrasound in sports medicine. Clin J Sport Med 2015; 25(1): 6–22.

47.

Mårtensson

Stener-Victorin

Wallin

. Acupuncture versus subcutaneous injections of sterile water as treatment for labour pain. Acta Obstet Gynecol Scand 2008; 87(2): 171–177.

48.

Lee

Gao

Collins

Mårtensson

Randall

Rowe

Kildea

. Caesarean delivery rates and analgesia effectiveness following injections of sterile water for back pain in labour: a multicentre, randomised placebo controlled trial. EClinicalMedicine 2020; 25: 100447.

49.

Lee

Mårtensson

Gao

Callaway

Barnett

Hellyer

Kearney

Kildea

. Sterile water injections for managing abdominal labour contraction pain: a randomised double blind placebo-controlled trial. Int J Nurs Stud 2026; 173: 105244.

50.

Muraca

Kramer

JLK

Butwick

. Sterile water injections for back pain in labour. BMJ 2024; 385: q1187.

51.

Chen

CPC

Suputtitada

. Regenerative and drug-free strategies for chronic musculoskeletal pain: an evidence-based perspective on shockwave therapy, high-intensity laser therapy and ultrasound-guided mechanical needling with sterile water injection. Biomedicines 2025; 13(11): 2801.

52.

Woolf

. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011; 152(3 suppl): S2–S15.

53.

Kalichman

Hunter

. Lumbar facet joint osteoarthritis: a review. Semin Arthritis Rheum 2007; 37(2): 69–80.

54.

Cass

. Ultrasound-guided nerve hydrodissection: what is it? A review of the literature. Curr Sports Med Rep 2016; 15(1): 20–22.

55.

Stecco

Schleip

. A fascia and the fascial system. J Bodyw Mov Ther 2016; 20(1): 139–140.