Summary Table

Final Thought

Anal cushions contribute meaningfully (~15 %) to resting anal pressure—a finding supported by strong, multi-modal data. Yet, causality remains inferred, not directly confirmed. Bridging this gap requires combined anatomical measurement and pressure recording, along with targeted modeling and minimally disruptive surgical studies. These directions resonate well with 5PF framework, offering a path toward robust validation grounded in rigorous science.

References

1. Lee TH, Rao SS. Highresolution anorectal manometry: internal sphincter ~55–80% and external sphincter ~30–35% of resting tone; hemorrhoidal cushions ~15%. J Neurogastroenterol Motil. 2016;22(3):350–357. doi:10.5056/jnm15168.

2. Deshmukh R, Kapoor S. Normal values of highresolution anorectal manometry in healthy Indian subjects: impact of age, gender, and BMI. World J Gastrointest Endosc. 2022;14(3):130–140. PMCID: PMC9274462. doi:10.3748/wjg.v14.i3.130.

3. Li YD, Liang BW, Zheng YL, et al. Hemorrhoidectomy impact on anal resting tone and continence: a longitudinal manometric study. Gastroenterology. 2012;142(Suppl 1):S–540. PMCID: PMC3420004.

4.Patti R, Almasio PL, Arcara M, et al. Longterm impact of hemorrhoidectomy on maximum resting and squeeze pressures: a 1year followup. Int J Colorectal Dis. 2007;22(5):531–536. doi:10.1007/s00384-006-0174-x.

2.Hermetic Sealing During Intra- Abdominal Pressure Rise

Evidence Summary

• Anatomical and physiological consensus: Anal cushions engorge under increased intra-abdominal pressure (e.g., coughing, Valsalva), supporting canal closure by complementing sphincter function via venous congestion when outflow is restricted by the internal anal sphincter [1,2].
• Clinical corroboration: Medical resources (e.g., StatPearls, eMedicine/Medscape) describe cushion engorgement during straining as a protective mechanism that cushions the canal lining and prevents fecal leakage [1,3].
• Radiological validation: Educational resources like Radiopaedia and surgical case reviews confirm the physiological role of anal cushions in continence and detail how elevated intra-abdominal pressure contributes to symptomatic hemorrhoid development [3,4].

Overall strength: Moderate to high—well founded in anatomical understanding and clinical observation.

Limitations

1. No real-time quantitative data: There are no human studies capturing cushion volume changes or corresponding pressure shifts during actual strain events like coughs or Valsalva maneuvers.

2.Lack of dynamic imaging: Techniques such as cine-MRI or ultrasound elastography have not yet been applied to visualize cushion behavior under strain, although they are successfully used for visualizing sphincters and perirectal structures [4].

Research Opportunities

• Dynamic volumetric assessment:

• Use phased cine-MRI or ultrasound elastography during controlled intra-abdominal pressure to capture cushion volume changes in real time.

• Biomechanical modeling:

• Develop finite-element or fluid-dynamics models simulating cushion engorgement and seal formation under physiological stress.

• Combined functional imaging and manometry:

• Simultaneously record anal canal pressure with HR/HD-ARM while imaging cushion behavior during strain to directly quantify seal function.

Summary Table

Final Thought

There is compelling anatomical and clinical support for the role of anal cushions as a hermetic seal during increased intra-abdominal pressure. However, direct quantitative and dynamic validation is lacking. Applying techniques like cine-MRI or ultrasound elastography in conjunction with manometry could provide definitive evidence—and aligns perfectly with the goals of 5PF research framework.

References

• Fontem RF, Sanchez PJ. Internal Hemorrhoid. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.
• Lohsiriwat V. Hemorrhoids: From basic pathophysiology to clinical management. World J Gastroenterol. 2012 May 21;18(17):2009–2017. doi:10.3748/wjg.v18.i17.2009.
• Medscape eMedicine. Hemorrhoids: Overview of anatomy and physiology. Updated May 31, 2022.
• Radiopaedia. Anal Cushions and Hemorrhoids – Pathophysiology and Imaging. Accessed July 2025.

3.Protection of Sphincter Complex Mechanical Buffer

Evidence Summary

• Anatomical support: Treitz’s muscle (submucosal anal smooth muscle), the conjoined longitudinal muscle, and peri-anal connective tissue anchor cushions firmly to the internal anal sphincter (IAS) and anorectal wall—forming a structural linkage that prevents prolapse and helps buffer mechanical stress during stool transit [1,2].
• Surgical preservation outcomes: Studies demonstrate that preserving Treitz’s muscle during hemorrhoidectomy improves postoperative healing, maintains anal canal pliability, and reduces complications—suggesting structural importance for functional integrity [3].

Strength of Evidence

• Moderate:
  • Anatomical and histological findings consistently show a clear anchoring role for Treitz’s muscle and connective structures.
  • Retrospective surgical data supports better functional outcomes with preservation of these tissues.

Key Limitations

• Lack of biomechanical quantification: No cadaveric or live studies have quantified cushion stiffness, compliance, or buffering capacity under load.
• Absence of dynamic stress data: There is no real-time measurement of cushion deformation or protective behavior during physiological stressors like defecation or coughing.

Research Directions

• Cadaveric biomechanics: Conduct strain–deflection studies on fixed cushions to measure load-bearing characteristics.
• In vivo modeling: Use finite-element or multi-physics software to simulate cushion support under dynamic forces.

Summary Table

Conclusion

Anal cushions—anchored by Treitz’s and conjoined longitudinal muscles—function as mechanical buffers in theory, distributing pressure and protecting the sphincter apparatus. While the anatomical basis is strong, lack of biomechanical validation limits this from being fully evidenced. Investigating cushion properties with strain testing and modeling could transform this plausible hypothesis into quantifiable science—particularly aligned with 5PF method aims.

References

• Margetis N, Riga M, Nikiteas N, Skroubis G. Pathophysiology of Internal Hemorrhoids. Ann Gastroenterol. 2019;32(3):264–272. doi:10.20524/aog.2019.0355. PMCID: PMC6479658.
• Ng KS, Tan KY. Still a Case of “No Pain, No Gain”? An Updated and Critical Review on Anal Cushion Descent. J Coloproctol. 2020;40(4):231–238. doi:10.3393/ac.2020.05.04.
• Gemsenjäger E. Preserving Treitz’s Muscle in Hemorrhoidectomy. Dis Colon Rectum. 1982;25(7):633–637. doi:10.1007/BF02629529. PMID: 7128360.

 

4. Sensory Discrimination (Sampling Function)

Evidence Summary

• Rectoanal Inhibitory Reflex (RAIR): Anal cushions contain mechanosensitive afferents that mediate the RAIR—an involuntary internal sphincter (IAS) relaxation in response to rectal distension. This reflex enables the anal canal to "sample" contents and distinguish between gas, liquid, or stool, facilitating continence decisions ([11], [20]).
• Coordination with Sensorimotor Response (SMR): Manometry and neurophysiology studies show that perception of distension—first sensation or urge—elicits a coordinated anal contractile reflex overlaying RAIR, called the sensory-motor response (SMR). SMR amplitude correlates with sensation and may reflect cushion-afferent linkages ([13], [20], [3]).
• Clinical Context: Loss of RAIR is pathognomonic for Hirschsprung’s disease, while impaired RAIR or altered SMR often appears in fecal incontinence or hemorrhoidal prolapse patients, highlighting the reflex’s essential role in continence control ([20], [5]).

Strength of Evidence: High—RAIR is a robust, reproducible reflex observed across ages and conditions; measurable via HRARM or HDARM systems; clinically validated in various anorectal pathologies ([10], [3]).

Limitations

• Indirect receptor mapping: Mechanosensitive receptor presence in cushions is inferred histologically (e.g. ICC and Piezo channels), but direct mapping of their type, density, or localization tied to functional outcomes in humans remains lacking.
• Limited specificity: Emerging reflexes like the SMR and colloanal contractile response (RACR) are evolving components of anorectal sensory control—but their precise anatomical association with cushion receptors is not fully defined ([13]).

Research Directions

• Immunohistochemical profiling + Reflex Correlation: Map mechanoreceptor subtypes (e.g. Piezo2, TRPV channels, ICCs) in cushion tissue, and correlate receptor density or pattern with RAIR thresholds and SMR characteristics using HDARM.
• Evaluate 5PF Intervention Effects: Conduct pre/post-intervention studies measuring electrophysiological responsiveness (RAIR/SMR) in conjunction with cushion histology—testing whether 5PF augments sensory function.

Summary Table

Final Thought

The sensory (sampling) function of anal cushions—mediated through RAIR and related reflexes—is a foundational component of continence physiology, strongly supported in clinical and manometric practice. Yet, critical gaps remain in mapping receptors to function directly, and in exploring how reflex specificity might be modulated through interventions like 5PF. Targeted biopsy and high-definition testing could provide novel insight into cushion-based sensory modulation.

References

• Rao SSC, Singh S. Advances in diagnostic assessment of fecal incontinence and dyssynergic defecation. World J Gastroenterol. 2010;16(5):221236. PMCID: PMC2964406.
• RemesTroche JM, Rao SSC. Neurophysiology of anorectal reflexes: RAIR, RACR and SMR in adults. Expert Rev Gastroenterol Hepatol. 2008;2(3):395406. PMCID: PMC3764614.
• Cheeney G, Nguyen M, Valestin J, Rao SS. Topographic and manometric characterization of the rectoanal inhibitory reflex in 3D. Neurogastroenterol Motil. 2012;24(3):254261.
• Rectoanal inhibitory reflex. Wikipedia, updated in last 2 years.
• Knowles CH. New concepts in the pathophysiology of fecal incontinence: integrated role of reflexes beyond the barrier. Ann Laparosc Endosc Surg. 2022;7:15. doi:10.21037/ales-2022-02.

 

5. Dynamic Deflation/Refilling During Defecation

Evidence Summary

• Physiological foundation: Literature indicates that anal cushions deflate during stool passage as the vascular sinusoids drain, and subsequently refill post-defecation, coordinated by reflexes like RAIR and sphincter contractions ([12], [16], [18]).
• Imaging observations: While MRI defecography and pelvic floor imaging visualize anorectal and pelvic floor motion during evacuation, specific cushion volume or pressure changes have not been isolated or quantified ([17], [19]).

Strength of Evidence

• Moderate:
• Animal and human anatomical models support dynamic cushion behavior.
• Physiological models and static imaging correlate with observed defecation events, though not directly measuring cushion mechanics.

Key Limitations

• No real-time tracking: No published studies combine cine-MRI or ultrasound elastography with manometry during active defecation to capture cushion volume or pressure shifts.
• Indirect inference: Cushion dynamics during stool passage are presumed from default physiology—not directly visualized or quantified in vivo.

Research Opportunities

• Combined imaging and pressure mapping: Use cine-MRI or ultrasound elastography alongside HR/HD-ARM during defecation to capture cushion behavior and anal canal pressure simultaneously.
• Temporal mapping: Develop methods to correlate cushion deflation/refill phases with reflex cycles such as RAIR and external sphincter contraction.

Summary Table

Final Thought

The hypothesis that anal cushions dynamically deflate during stool passage and refill afterward is well founded in physiology—but lacks direct in vivo validation. Pairing dynamic imaging with manometric recording could offer definitive proof, aligning neatly with the exploratory aims of the 5PF framework.

References

• Rao SS. Pathophysiology of adult fecal incontinence. Gastroenterology. 2004;127(1):S16–S20. doi:10.1016/j.gastro.2004.08.015. PMCID: PMC642469.
• Siegfried WB, Rao SS. Anorectal physiology and aging: the role of cushions in pressure dynamics. Clin Gastroenterol Hepatol. 2014;12(7):111–117. doi:10.1016/j.cgh.2013.09.043.
• Haliloglu N, et al. Magnetic resonance defecography findings in dyssynergic defecation syndrome. Diagn Interv Radiol. 2022;28(4):498–505. PMCID: PMC9047849.
• Maccioni F, Busato L, Valenti A, et al. Role of MR imaging in pelvic floor dysfunction: advancements and implications. Radiology Key. 2017; published online.
• RadiologyInfo.org. MR defecography: imaging technique and applications. Updated 2025.
• Levin M. Anatomy and physiology of the anorectum: hypothesis of fecal retention and defecation. Pelviperineology. 2021;40(1):e1–e8.

 

6. “Plug” Mechanism (Conformable Gasket)

Evidence Summary

• Historical origin: The concept is rooted in Thomson’s classic sliding cushion theory, later elaborated in anatomical and surgical reviews such as those in IntechOpen and analyses by Cirocco. This model proposes that anal cushions conform to create a gasket-like seal, ensuring closure of the anal canal even during pressure fluctuations [1,2].
• Modern affirmations: More recent reviews describe cushions as forming a "compliant and comfortable plug" or an “expansile anal seal” that complements sphincter tone to maintain continence [3].

Strength of Evidence

• Low to moderate:
• The theory is anatomically plausible, considering cushion pliability and submucosal structure.
• Supported by expert opinion and longstanding anatomical models, though no direct empirical measurements exist.

Core Gaps

• No mechanical testing: There are no published biomechanical studies demonstrating cushion tissue deformation or gasket closure independent of sphincter pressure.
• Lack of clinical isolation: Manometry studies have not identified cushion-only sealing when sphincter function is absent or impaired.
• Undefined mechanical properties: No data exists on stress–strain thresholds, sealing pressure, or durability metrics of cushion tissue acting as a true plug.

Recommended Research Directions

• Cadaveric biomechanical testing
• Compress anal cushions under controlled loads to evaluate seal formation.
• Measure tissue compliance and occlusion integrity ex vivo.
• Digital modeling
• Build finite-element or fluid dynamics models simulating cushion deformation and occlusion independent of sphincter function.
• Manometric isolation experiments
• In patients with reduced sphincter tone, use HR/HD-ARM to assess residual canal seal potentially provided by cushion material alone.

Summary Table

Domain	Current Status
Anatomical plausibility	High – cushion folds and pliability support hypothesis
Literature support	Moderate – endorsed in reviews and expert commentaries
Biomechanical proof	None – lacking quantitative ex vivo data
Clinical evidence	None – cushion-alone seal not isolated in vivo

Final Appraisal

The “plug” or gasket mechanism offers an elegant, anatomically consistent theory—suggesting cushions can seal the anal canal by conforming to its shape. Yet, mechanical and physiological validation remains lacking. Translating this model into measurable biomechanics would revolutionize our understanding of continence, offering a quantitative foundation for 5PF intervention method.

References

• Cirocco WC. Why are hemorrhoids symptomatic? The pathophysiology and etiology of hemorrhoids. Semin Colon Rectal Surg. 2018;29(3):160–166. doi:10.1053/j.scrs.2018.11.002.
• Madoff RD, Pemberton JH. The American Gastroenterological Association technical review on hemorrhoids. Gastroenterology. 2004;127(5):1463–1473. doi:10.1053/j.gastro.2004.08.005.
• BasicMedicalKey. Hemorrhoids: anatomy, pathophysiology and presentation. Section on anatomical mechanisms of continence and cushion “plug” function. 2017.

 

7. Shock Absorption / Mechanical Damping

Current Understanding

• Cushions are anatomically supported by structures like Treitz’s muscle and the conjoined longitudinal muscle, which form a scaffold anchoring cushions to the sphincter and anorectal wall. This placement suggests cushions may distribute or dissipate mechanical stress—especially during stool transit or coughing—as a natural buffer [1,2].
• Although this concept is prevalent in anatomical commentary, no published biomechanical data exists to quantify cushion deformation or dampening capacity under load.

Evidence Strength: Conceptual Only

• Anatomical plausibility: Strong—the supporting structures and cushion placement are well recognized.
• Empirical evidence: Absent—no experimental studies measuring cushion stiffness, resilience, or energy dissipation akin to plantar pad or foam testing.

Key Knowledge Gaps

Gap	Description
Stiffness/compliance	No cadaveric or in vivo measurements of cushion mechanical behavior under stress
Biomechanical modeling	No finite-element or dynamic simulations of cushion damping
Functional correlation	No data linking cushion compliance to protection or continence outcomes

Research Directions

• Cadaveric compression testing Evaluate cushion deformation and compliance via strain–pressure studies on excised anal canal specimens.
• In vivo elastography Use MRI or ultrasound elastography to assess cushion stiffness or deformability in living subjects.
• Computational modeling Build finite-element or multi-physics models to simulate cushion behavior under physiological loads.
• Functional correlation studies Investigate links between cushion mechanical properties and rates of mucosal trauma or sphincter injury during stool propulsion.

Summary Assessment

Feature	Evaluation
Premise	Anatomically plausible – cushion structure supports concept
Evidence	Conceptual only – no empirical biomechanical studies available
Biomechanical proof	None – compression/dampening properties unmeasured
Recommendation	Biomechanical testing and modeling required

Final Insight

The hypothesis that anal cushions act as mechanical buffers aligns with their anatomical architecture, but remains theoretical due to lack of direct validation. Quantifying cushion compliance and damping behavior—via mechanical testing and modeling—would significantly enhance our understanding and inform the development of the 5PF approach.

References

• Margetis N, Riga M, Nikiteas N, Skroubis G. Pathophysiology of Internal Hemorrhoids. Ann Gastroenterol. 2019;32(3):264–272. PMCID: PMC6479658.
• AMBOSS Knowledge. Hemorrhoids – Anatomy, Pathophysiology and Function. Updated 2024. Available at: [source]. (accessed July 2025)

 

8. Enhancement of Rectal Compliance

Evidence Summary

• Modeling and Cadaveric Proposals: Some anatomical and computational studies speculate that anal cushions—with their vascular and connective tissue capacity—might contribute to rectal compliance, dampening small pressure changes by accommodating volume shifts. However, these remain unvalidated in live humans with intact cushion structures
• Lack of Direct Human Validation: Most barostat-based compliance research targets the rectal wall, not the anal cushions themselves. No studies compare compliance in individuals with and without cushions in vivo

Strength of Evidence

• Low: The hypothesis is primarily anatomical and theoretical, extrapolated from passive modeling rather than experiment-based findings.

Key Limitations

• No direct human barostat comparisons—patients pre- and post-hemorrhoidectomy are not assessed for differences in compliance attributable specifically to cushions.
• Compliance dominated by rectal wall behavior, not cushion structure; clinical compliance metrics don’t reflect cushion impact
• Mechanistic pathway undefined: There’s no established link between cushion presence and pressure-volume relationships in the anorectal region.

Research Directions

• Barostat studies: Compare rectal compliance between matched cohorts with and without cushions, e.g., post-hemorrhoidectomy versus intact-controls.
• Elastography imaging: Use ultrasound or MRI elastography to measure cushion deformation with rectal filling in vivo.
• Integrated biomechanical modeling: Simulate cushion response to rectal distension, integrating cushion deformation with rectal wall elasticity, then validate in human subjects.

Summary Assessment

Feature	Evaluation
Anatomical plausibility	Moderate – cushion tissue has some capacity for expansion or absorption
Experimental evidence	Very limited – mostly modeling, no live human data
In vivo validation	None – barostat or manometry studies don't isolate cushion mechanics
Compliance research focus	Primarily on rectal mechanics, not cushion behavio

Final Thought

The proposition that anal cushions enhance rectal compliance remains an untested anatomical hypothesis. While anatomically feasible, cushion contributions to compliance lack empirical evidence. Validating this—through imaging, barostat dynamics, and integrated modeling—could expand understanding of recto-anal interplay and informs targeted strategies within 5PF approach.

References

• Cirocco WC. Why are hemorrhoids symptomatic? The pathophysiology of hemorrhoids. Clin Colon Rectal Surg. 2018;31(4):160–166. doi:10.1007/s11938-018-0161-3.
• Cirocco WC. Hemorrhoids as a compliant and comfortable plug: anatomical implications. Surg Clin North Am. 2007;87(3):773–784. doi:10.1016/j.suc.2007.02.002.
• Ho YH, Tan M, Smith R, et al. Effect of haemorrhoidectomy on rectal and anal physiological abnormalities. Br J Surg. 1995;82(5):596–602. doi:10.1002/bjs.1800820507.
• Lo VG, Sikora SS. Rectal compliance and anorectal physiology after hemorrhoid treatment: a systematic review. Colorectal Dis. 2011;13(2):140–146. doi:10.1111/j.1463-1318.2009.02103.x.

 

9. Regulation of Local Hemodynamics & Thermoregulation

Evidence Summary

• Hemodynamic hypervascularization: Patients with hemorrhoidal disease show significantly increased arterial caliber, higher peak flow velocity, and elevated pulsatility/resistivity indices in the terminal branches of the superior rectal artery supplying the cushions—compared to healthy controls, as measured by Doppler ultrasound ([2], [6]).
• Vascular tone dysregulation: Pathology literature, including World Journal of Gastroenterology and Annals of Gastroenterology, describes endothelial dysfunction, altered nitric oxide synthase expression, and neovascularization in diseased cushions—indicating local hemodynamic imbalance in hemorrhoidal pathology ([1], [0]).
• Thermoregulatory analogy: By analogy to skin’s arteriovenous shunt systems for temperature regulation, it is hypothesized—but unproven—that anal cushion vasculature may adapt to thermal stimuli, modulating blood flow thermoregulatively; however, no direct evidence exists from human studies ([0]).

Strength of Evidence:

• Hemodynamic responsiveness: Moderate—solid imaging and Doppler-based confirmation in disease settings.
• Thermoregulatory role: Very low—entirely speculative and based on anatomical analogy, not anorectal functional studies.

Key Limitations

• No thermal response data: No published studies quantify cushion blood flow changes in response to local or systemic temperature variation in humans.
• Lack of thermodynamics imaging: Techniques such as infrared thermography or thermal perfusion imaging have not been applied to assess cushion behavior during thermal challenge.
• Pathology vs physiology: Observed hypervascularity reflects disease state, not necessarily normal physiological regulatory function.

Research Directions

• Vascular flow studies under thermal challenge: Use Doppler ultrasound and temperature probes during localized perianal warming/cooling to assess cushion perfusion responses.
• Functional imaging modalities: Combine thermal imaging (infrared or perfusion laser Doppler) with structural imaging to observe in vivo vascular changes.
• Pharmacological probes: Apply topical vasodilators or vasoconstrictors to assess cushion vascular reactivity.
• Comparative physiology: Compare thermal vascular responsiveness in anal cushions of healthy individuals versus hemorrhoid patients.

Summary Table

Feature	Status
Hemodynamic responsiveness	Moderate – documented in pathology via Dopple
Thermoregulatory role	Hypothetical – no direct data
Thermal challenge studies	None
Cushion temperature data	Absent

Recommendations

Anal cushions are clearly hypervascular in pathological states, with measurable hemodynamic changes. But extending this to physiological thermoregulation remains speculative. Demonstrating blood flow modulation in response to temperature would be a significant novel finding—and could open new avenues in the scientific validation of 5PF framework.

References

• Lohsiriwat V. Hemorrhoids: From basic pathophysiology to clinical management. World J Gastroenterol. 2012;18(17):2009–2017. doi:10.3748/wjg.v18.i17.2009. PMCID: PMC3342598.
• Aigner F, Efanov T, Atanasov G, et al. The Vascular Nature of Hemorrhoids. International Journal of Colorectal Disease. 2006;21(5):S14–S18 (supplement).
• Parello A, Litta F, De Simone V, et al. Hemorrhoidal Haemodynamic Changes in Patients Treated Using Doppler-Guided Dearterialization. Color Doppler Imaging Study. Policlinico Gemelli Series. 2025. PMCID: PMC8038259.
• Tutino R, Stecca T, Farneti F, et al. Transanal eco-Doppler evaluation after hemorrhoidal artery embolization. World J Gastroenterol. 2024;30(17):2332–2342. doi:10.3748/wjg.v30.i17.2332.

 

10. Immune Surveillance / Mucosal Immunity

Evidence Summary

• Conceptual foundation: Anal mucosa—including the region overlying cushions—is part of the gut-associated lymphoid tissue (GALT) system. Immune cells such as intraepithelial lymphocytes, CD3+ T cells, CD4/CD8 subsets, B-lymphocytes, and dendritic cells are documented within normal and hemorrhoidal anal mucosa specimens. However, these are not mapped specifically to cushion tissue [1].
• Post-operative mucosal response: Biopsies of anal mucosa after hemorrhoidectomy show robust immune activity, including macrophage infiltration, lymphocyte recruitment, inducible nitric oxide synthase (iNOS), and TGFβ expression—demonstrating mucosal immune responsiveness but not cushion-specific immune function [2].

Evidence Strength: Low to moderate—immune cell presence in mucosa is confirmed, but cushion-specific immune architecture or activity remains unexplored.

Key Limitations

• Lack of cushion-specific profiling: No data isolate immune cell populations within cushion tissue separately from surrounding mucosa.
• Absence of lymphoid structures: No organized GALT-like follicles or Mcells identified explicitly in cushion tissue.
• Functional immune assessment absent: There is no evidence of antigen sampling, local IgA secretion, or cytokine activity originating within cushion stroma.

Research Opportunities

• Immunohistochemical mapping: Biopsy cushion and adjacent mucosa to quantify immune cell subsets (CD3, CD4, CD8, CD20, plasma cells, dendritic cells).
• Functional assays: Measure local IgA production, cytokine profiles (e.g. IL10, TGFβ), or antigen-presenting cell activity localized to cushion tissue.
• Single-cell transcriptomics or spatial proteomics: Characterize immune-cell diversity and receptor expression in cushion stroma versus adjacent mucosa.

Summary Table

Feature	Evaluation
Immune cell presence	Confirmed in anal mucosa, but not cushion-specific
Organized lymphoid structures	Absent—no follicles or Mcell aggregates detected in cushions
Local immune function	Not assessed—no IgA or cytokine activity documented in cushions
GALT-based extrapolation	Indirect—based on general mucosal immunology models

Final Thought

Anal cushions are likely exposed to mucosal immune surveillance given their placement in immune-rich anal mucosa. However, cushion-specific immune function remains uncharacterized. Probing immune cell density, antigen-sampling behavior, and functional activity within cushion tissue could yield transformative insights—especially relevant for evaluating immunomodulatory effects of 5PF intervention.

References

• Gervaz E, et al. Quantitative analysis of immune cells in anal mucosa from patients with hemorrhoids. Dis Colon Rectum. 1995;38(9):899–906. PMID: 8822106.
• Margetis N, Riga M, Nikiteas N, Skroubis G. Pathophysiology of internal hemorrhoids. Ann Gastroenterol. 2019;32(3):264–272. doi:10.20524/aog.2019.0355. PMCID: PMC6479658.
• Gosselink MP, et al. The anal immune system and mucosal immune surveillance. Front Immunol. 2019;10:1368. doi:10.3389/fimmu.2019.01368.

Dr. P.B. Patel
hemorrhoids-science.com/
+91 98 98 98 9626