IMMUNE OS ATLASby AllerimSign in

neuroimmune

Substance P

Sensory neuropeptide that can couple pain, itch, vascular leak, and mast-cell-rich barrier inflammation

neuropeptidesensory nervesmast cellitchpainneurogenic inflammation

Review layer

Last reviewed 2026-07-03

emergingclinical context required

Neuroimmune mediators are modeled as directional teaching nodes for threshold, reflex, sensory, vascular, and tissue-crosstalk behavior. Use as educational systems context, not diagnosis or treatment guidance.

4 review sources

State signature

Systems profile

Inflammation86
Tolerance45
Metabolism54
Tissue88
Neuroimmune80
Chronicity48

System effects

Primary mapped axes from existing Atlas data.

Interpretive

Tissue

High 88

Organ, barrier, stromal, vascular, or local niche behavior.

neurogenic inflammationvascular permeabilityitch and flare physiologybarrier stress amplification

Inflammation

High 86

Inflammatory alarm, recruitment, mediator release, or tissue-damaging amplification.

can lower mast-cell activation thresholdscan promote histamine and cytokine release in susceptible tissue contextslinks nociceptive signaling with local innate immune amplification

Neuroimmune

High 80

Nerve, neuropeptide, autonomic, microglial, pain, itch, fatigue, or sickness-behavior coupling.

sensory neuronstrigeminal afferentsdorsal root gangliaenteric and cutaneous nerve endings

Local map

Relationship field

Arrows point from the upstream source toward the receiving target. Restraint edges use a bar; association edges stay dashed because they are not causal arrows.

Substance P
Mast CellSkin Immune Ecosystem

Selected relationship

Activation

Sensory-neuron substance P can lower mast-cell activation thresholds and amplify mediator release in neurogenic inflammation models

Read as source increases target activity, recruitment, or threshold crossing.

What this relationship means

Read this as a threshold-lowering edge: Substance P can make Mast Cell more ready to fire in the right tissue context.

Effect of source

Substance P represents the nervous-system signal entering the immune map.

Effect on target

Mast Cell is the receiving immune cell whose activation or mediator release may become easier.

Use with caution

This is mechanism education, not a diagnosis, severity score, or treatment rule.

System effect

Substance P influences Mast Cell; the axes below show which mapped systems carry that relationship.

Activation effect

Inflammation

High 86

Inflammatory alarm, recruitment, mediator release, or tissue-damaging amplification.

histaminetryptase+19 more

Tissue

High 88

Organ, barrier, stromal, vascular, or local niche behavior.

GutLung+17 more

Metabolism

Light 54

Energy allocation, glycolysis, mitochondrial strain, lipid signaling, or nutrient-sensitive behavior.

glycolytic burstmitochondrial ROS signaling+1 more

Axes are mapped cues from Atlas data, not clinical predictions.

Evidence context

Curated edge, reviewed endpoints, and mapped external anchors.

Atlas edge
Substance P - reviewed 2026-07-03 - emergingMast Cell - reviewed 2026-05-17 - well-supported2 external anchors
Reactomehigh+1 more

Fc epsilon receptor (FCERI) signaling

R-HSA-2454202 - checked 2026-06-28

Graph neighborhood

Direct relationships

Full graph

Arrow shows upstream source toward receiving target.

Sensory-neuron substance P can lower mast-cell activation thresholds and amplify mediator release in neurogenic inflammation models

Arrow shows upstream source toward receiving target.

Itch and pain fibers can use substance P to couple local neurogenic inflammation with skin barrier reactivity

Mediator interpretation

Effect Of and Effect On

Substance P is modeled as a sensory-neuron output that can lower mast-cell and barrier-tissue thresholds. It helps explain why pain, itch, stress, tissue injury, and inflammation can reinforce each other in local neuroimmune loops.

What this means

Effect of the nervous signal

Read Substance P as a sensory-neuron release signal: pain, itch, irritants, stress, or tissue injury may be feeding the immune threshold, not just responding to it.

Effect on immune and tissue systems

On immune and tissue systems it usually means mast cells, vessels, and barrier tissues may be easier to trigger, amplifying itch, flare, swelling, or local cytokine output.

Use it in Atlas when

Use this node when symptoms look neurogenic and inflammatory at the same time, especially around barrier tissues.

Boundary

This does not prove a mast-cell disorder, migraine mechanism, allergy, or treatment target by itself.

Influence Trace

Nervous signal to immune behavior

Guided path

What starts the signal?

Pain, itch, irritant exposure, tissue injury, or stress-sensitive sensory-neuron firing.

What receives it?

Mast cells and barrier tissues that carry neuropeptide-sensitive activation thresholds.

What changes in the system?

The local tissue can become easier to flare, itch, leak fluid, or release mast-cell mediators.

What should not be over-interpreted?

Do not read this as proof of allergy, mast-cell disease, migraine mechanism, or a treatment target without clinical context.

  1. 1Sensory neuron releaseSubstance P

    Substance P carries a pain or itch-linked nerve signal into the tissue immune map.

  2. 2Mast-cell thresholdMast Cell

    Mast cells become the receiving amplifier when the local context lowers activation thresholds.

  3. 3Skin and barrier behaviorSkin Immune Ecosystem

    Barrier tissues can show itch, flare, vascular leak, and cytokine amplification.

Effect of

sensory neuronstrigeminal afferentsdorsal root gangliaenteric and cutaneous nerve endings

Regulated by

tissue injurystress loadirritant exposurenociceptor activation

Signals through

NK1R / TACR1MRGPRX2 mast-cell activation context

Effect on immune cells

can lower mast-cell activation thresholdscan promote histamine and cytokine release in susceptible tissue contextslinks nociceptive signaling with local innate immune amplification

Effect on tissues

neurogenic inflammationvascular permeabilityitch and flare physiologybarrier stress amplification

Nervous-system behavior

pain signalingitch signalingsensory gainstress-sensitive neuroimmune amplification

tachykinin neuropeptide

Clinical Context Boundaries

itch and urticaria-like barrier loopsmigraine-adjacent neurogenic inflammationpain-inflammation coupling