Neuroanatomy as a design language.

Historical foundations — Denslow & Korr, 1947–1981

1. 01
   Denslow, Korr & Krems — 1947EXPERIMENTAL EVIDENCE

   Quantitative 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.

2. 02
   Korr, Wright & Thomas — 1962EXPERIMENTAL EVIDENCE

   Effects 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.

3. 03
   Korr, Wright & Chace — 1964CLINICAL OBSERVATION

   Cutaneous 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.

4. 04
   Korr, Wilkinson & Chornock — 1967EXPERIMENTAL EVIDENCE

   Axonal 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.

5. 05
   Korr — 1975HISTORICAL MODEL

   Proprioceptors 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.

6. 06
   Korr — 1976HISTORICAL MODEL

   The 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.

7. 07
   Korr — 1979HISTORICAL MODEL

   The 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.

8. 08
   Korr — 1979HISTORICAL MODEL

   The 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.

9. 09
   Korr — 1981HISTORICAL MODEL

   The 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

1. 01
   Ständer et al. — 2024MODERN EVIDENCE

   Skin 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.

2. 02
   Glatte et al. — 2019MODERN EVIDENCE

   Architecture 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.

3. 03
   Marek-Jozefowicz et al. — 2023MODERN EVIDENCE

   Molecular 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.

4. 04
   Siiskonen & Harvima — 2019MODERN EVIDENCE

   Mast 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.

5. 05
   Ortiz Flores & Kashem — 2026MODERN EVIDENCE

   When 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.

6. 06
   Reynolds et al. — 2000MODERN EVIDENCE

   Molecular 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.

7. 07
   Maday et al. — 2014MODERN EVIDENCE

   Axonal 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.

8. 08
   Dilley et al. — 2005EXPERIMENTAL EVIDENCE

   Pressure 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.

9. 09
   Ellis et al. — 2021MODERN EVIDENCE

   Neurodynamics: 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.

10. 10
    Lee et al. — 2008MODERN EVIDENCE

    An 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.

11. 11
    Lowy et al. — 2021MODERN EVIDENCE

    Cutaneous 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.

12. 12
    Feng et al. — 2024MODERN EVIDENCE

    Sensory 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.

13. 13
    Bonezzi et al. — 2020MODERN EVIDENCE

    Capsaicin 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?