Science
Relevant articles.
The publications behind the SIRIAM theoretical framework. Each article is linked to its source, with a summary of what was investigated and its specific relevance to the SIRIAM research rationale.
Scientific foundations
From segmental neurophysiology to the neurodermal interface.
The SIRIAM framework builds on decades of research into segmental neurophysiology, afferent input, autonomic regulation and neurotrophic communication. Each publication below is linked, with its contribution and its specific relevance to the SIRIAM research rationale. Historical interpretations are labelled as such; nothing here is presented as evidence of product efficacy.
Historical foundations — Denslow & Korr, 1947–1981
- 01Denslow, Korr & Krems — 1947EXPERIMENTAL EVIDENCEQuantitative Studies of Chronic Facilitation in Human Motoneuron Pools
American Journal of Physiology, 150(2), 229–238 · View publication ↗
A quantitative comparison of motor-neuron responsiveness across spinal segments. Reflex thresholds proved non-uniform: certain segments showed increased responsiveness — the experimental basis of what became known as segmental facilitation.
Relevance to SIRIAM · Historical support for investigating the body in terms of segmental neural organization, rather than considering each anatomical structure in isolation.
- 02Korr, Wright & Thomas — 1962EXPERIMENTAL EVIDENCEEffects of Experimental Myofascial Insults on Cutaneous Patterns of Sympathetic Activity in Man
Acta Neurovegetativa, pp. 329–355 · View publication ↗
Musculoskeletal input was experimentally altered (hypertonic saline, heel lifts, postural change) while electrical skin resistance over thoracic and lumbar regions was mapped. Referred pain produced new low-resistance areas within the referred region and in related dermatomes.
Relevance to SIRIAM · Altered musculoskeletal input → segmental neural processing → measurable changes at the skin. This relationship is directly relevant to the investigation of the neurodermal interface.
- 03Korr, Wright & Chace — 1964CLINICAL OBSERVATIONCutaneous Patterns of Sympathetic Activity in Clinical Abnormalities of the Musculoskeletal System
Acta Neurovegetativa · PubMed record ↗
130 patients with musculoskeletal disturbances, myofascial stresses and pain syndromes were studied with electrical skin resistance mapping alongside clinical, radiographic, electromyographic and palpatory assessment. Segmental low-resistance areas frequently appeared in referred-pain regions and related dermatomes.
Relevance to SIRIAM · The historical chain — musculoskeletal system → segmental neural organization → sympathetic nervous system → dermatomal skin response. Arguably the single most relevant historical Korr paper for SIRIAM LAB.
- 04Korr, Wilkinson & Chornock — 1967EXPERIMENTAL EVIDENCEAxonal Delivery of Neuroplasmic Components to Muscle Cells
Experimental neurobiology · PubMed record ↗
Opened a second direction in Korr's work: axonal transport and neurotrophic function. The nerve is not merely an electrical conductor but a biological pathway transporting molecular material between neuronal and peripheral environments.
Relevance to SIRIAM · Introduces the principle that neural communication is not exclusively electrical — axonal transport biologically connects neuronal health with peripheral tissue biology.
- 05Korr — 1975HISTORICAL MODELProprioceptors and Somatic Dysfunction
Journal of the American Osteopathic Association, 74(7), 638–650 · PubMed record ↗
The role of mechanoreceptors and proprioceptive input in somatic dysfunction, modelled around altered muscle-spindle and segmental neural activity — the afferent side of the system: mechanical state → receptor activity → afferent signalling → spinal processing → altered efferent behaviour.
Relevance to SIRIAM · The specific historical model should be read as a hypothesis, but the broader principle that afferent input influences central and autonomic processing is fundamental neuroscience.
- 06Korr — 1976HISTORICAL MODELThe Spinal Cord as Organizer of Disease Processes: Some Preliminary Perspectives
JAOA, 76(1), 35–45 · PubMed record ↗
Describes the spinal cord not as a passive relay but as an integrative neural structure receiving and processing large quantities of peripheral information.
Relevance to SIRIAM · Marks the transition from a linear model (brain → nerve → tissue) to an interacting network: skin ↔ peripheral nerve ↔ spinal segment ↔ autonomic system ↔ tissue.
- 07Korr — 1979HISTORICAL MODELThe Spinal Cord as Organizer of Disease Processes II: The Peripheral Autonomic Nervous System
JAOA · PubMed record ↗
Indexed across afferent pathways, peripheral nerves, musculoskeletal innervation, sympathetic and parasympathetic nervous systems, and spinal cord physiology/pathophysiology.
Relevance to SIRIAM · Brings together the three pillars central to the SIRIAM anatomical model: peripheral nerve + spinal organization + autonomic regulation.
- 08Korr — 1979HISTORICAL MODELThe Spinal Cord as Organizer of Disease Processes III: Hyperactivity of Sympathetic Innervation as a Common Factor in Disease
JAOA · PubMed record ↗
Proposed that sustained regional sympathetic hyperactivity could influence peripheral tissue function and contribute to pathological processes.
Relevance to SIRIAM · Relevant because the skin is densely autonomically regulated through vasomotor and sudomotor pathways. The disease implications are labelled explicitly as a historical hypothesis, not established causal evidence.
- 09Korr — 1981HISTORICAL MODELThe Spinal Cord as Organizer of Disease Processes IV: Axonal Transport and Neurotrophic Function in Relation to Somatic Dysfunction
JAOA, 80(7), 451–459 · PubMed record ↗
Unites Korr's two research lines: afferent input → spinal/autonomic processing, and neuron → axonal transport → peripheral tissue, discussing neurotrophic function in relation to neurons, muscles and biomechanical phenomena.
Relevance to SIRIAM · Invites investigation of peripheral nerves as more than electrical transmission structures: they maintain the biological relationship between neural and target tissues.
Modern neuroscience — 2000–2026
- 01Ständer et al. — 2024MODERN EVIDENCESkin Innervation
Review — cutaneous neuroanatomy · PubMed record ↗
A near-ideal modern starting reference. All skin layers and appendages are richly innervated by afferent and efferent neurons; sensory nerves register external and internal stimuli, autonomic fibres influence perfusion and sweat secretion. The precise molecular classification of human cutaneous afferents remains incomplete.
Relevance to SIRIAM · Supports the position that the skin is a densely innervated peripheral neurobiological interface — sensory organ, autonomic effector organ and neural interface in one.
- 02Glatte et al. — 2019MODERN EVIDENCEArchitecture of the Cutaneous Autonomic Nervous System
Frontiers in Neurology · Full text ↗
Detailed anatomical description of small cutaneous nerve fibres — Aβ, Aδ and C fibres — together with autonomic innervation around vessels and skin appendages.
Relevance to SIRIAM · Confirms that the skin is anatomically a fine-meshed sensory-autonomic neuronal organ.
- 03Marek-Jozefowicz et al. — 2023MODERN EVIDENCEMolecular Mechanisms of Neurogenic Inflammation of the Skin
Review — neurogenic inflammation · PubMed record ↗
Activation of TRPV channels on sensory nerves triggers release of neuropeptides such as CGRP and Substance P, which act on blood vessels, immune cells, mast cells and keratinocytes — with feedback toward sensory neurons. Not one-way traffic: SKIN → NERVE → SKIN.
Relevance to SIRIAM · A very strong biological foundation: sensory nerves themselves can actively alter local tissue biology.
- 04Siiskonen & Harvima — 2019MODERN EVIDENCEMast Cells and Sensory Nerves
Frontiers in Cellular Neuroscience · Full text ↗
Describes a reciprocal mast cell–sensory nerve loop: neural mediators influence mast cells, while mast-cell mediators can sensitise nerve endings.
Relevance to SIRIAM · Details the bidirectional signalling loop underlying the neurodermal interface concept.
- 05Ortiz Flores & Kashem — 2026MODERN EVIDENCEWhen Stress Signals to Skin: Sympathetic Nerves Tune Immune Surveillance
Review — sympathetic–epithelial–immune signalling · PubMed record ↗
Describes a mechanism in which sympathetic signalling via epidermal keratinocytes influences the positioning of tissue-resident memory T cells: sympathetic nerve → keratinocyte → immune-cell behaviour.
Relevance to SIRIAM · Remarkably close to the functional neurodermal interaction SIRIAM investigates — a direct modern extension of the historical Korr skin-resistance studies.
- 06Reynolds et al. — 2000MODERN EVIDENCEMolecular Mechanisms Regulating the Retrograde Axonal Transport of Neurotrophins
Review — axonal transport · PubMed record ↗
Neurotrophins released by target tissues bind receptors on nerve terminals and are transported via the axon to the neuronal cell body, where they influence gene expression and neuronal survival: PERIPHERY → NEURON, not only the reverse.
Relevance to SIRIAM · Demonstrates that neural communication has a biological, molecular dimension in both directions — a modern confirmation of Korr's second research line.
- 07Maday et al. — 2014MODERN EVIDENCEAxonal Transport: Cargo-Specific Mechanisms of Motility and Regulation
Neuron · PubMed record ↗
Key modern review: anterograde transport carries proteins, lipids and synaptic components toward the distal axon; retrograde transport returns signalling endosomes to the soma. Axonal transport is essential for neuronal homeostasis.
Relevance to SIRIAM · Strong as a fundamental neurobiological concept. It does not show that a topical cosmetic is transported retrogradely along a peripheral nerve — that would require tracing the molecule itself.
- 08Dilley et al. — 2005EXPERIMENTAL EVIDENCEPressure and Stretch Mechanosensitivity of Peripheral Nerve Fibres Following Local Inflammation
Journal of Physiology · Full paper ↗
When peripheral nerves were locally inflamed, nerve fibres responded more strongly to mechanical pressure and slight stretch: local neuritis → altered axonal physiology → increased mechanical sensitivity.
Relevance to SIRIAM · Supports that peripheral nerves are mechanically responsive biological tissues whose sensitivity can change with local inflammatory or pathological conditions. Whether skin treatment above a nerve changes its mechanosensitivity must be tested separately.
- 09Ellis et al. — 2021MODERN EVIDENCENeurodynamics: Is Tension Contentious?
Review — neurodynamics · PubMed record ↗
States explicitly that neurodynamics should no longer be regarded as a purely mechanical 'gliding of a nerve': mechanisms can also be neuroimmune, neurochemical and neurophysiological. Neurodynamic tests are useful but their diagnostic specificity is not perfect.
Relevance to SIRIAM · A strong modern bridge to Korr's ideas on mechanical loading of neural tissue — with the necessary clinical nuance.
- 10Lee et al. — 2008MODERN EVIDENCEAn Evidence-Based Approach to Human Dermatomes
Clinical Anatomy · PubMed record ↗
Analysed the evidence behind classical dermatome maps and concluded that many common charts rest on problematic or inconsistent historical data. Proposes an evidence-based map emphasising overlap, interindividual variability and areas of consistency rather than absolute boundaries.
Relevance to SIRIAM · Crucial for the SIRIAM Atlas: a dermatome is presented as a predominant cutaneous territory or reference field, acknowledging physiological overlap and interindividual variability.
- 11Lowy et al. — 2021MODERN EVIDENCECutaneous Neuroimmune Interactions in Peripheral Neuropathies
Review — neuroimmune interaction · Full text ↗
The nervous and immune systems influence each other bidirectionally via cytokines, inflammatory mediators, neuropeptides, sensory neurons and immune cells; dysregulation is associated with both skin conditions and peripheral neuropathies.
Relevance to SIRIAM · Frames the skin as a neuro–immune–epithelial unit rather than three separate systems.
- 12Feng et al. — 2024MODERN EVIDENCESensory Neuronal Control of Skin Barrier Immunity
Review — cutaneous immunity · Full text ↗
Sensory neurons play an active role in regulating the cutaneous immune barrier and communicate with multiple immune-cell populations in homeostasis, injury and infection.
Relevance to SIRIAM · Direct neuroimmune communication — one of the five key modern references alongside the historical Korr line.
- 13Bonezzi et al. — 2020MODERN EVIDENCECapsaicin 8% Dermal Patch
Review — topical neuromodulation · PubMed record ↗
A proof-of-principle example: capsaicin applied to the skin acts on TRPV1 receptors of peripheral nociceptive fibres, with its effect explained through local modulation of small afferent nerve fibres.
Relevance to SIRIAM · Proves the general principle that topically applied molecules can modify peripheral sensory nerve function — but molecule-specifically: capsaicin → TRPV1 receptor → nociceptor. For every SIRIAM component the same question must be asked: is there a biologically plausible cutaneous or neural target?
SIRIAM hypothesis
The individual components of the neurodermal model are well established. Whether specifically designed topical formulations can reproducibly influence defined peripheral neural territories remains an experimental question under investigation by SIRIAM LAB.