Pain neuropeptide
Neurogenic inflammation↓
Also searched as Neurogenic inflammation.
Named on the fibromyalgia and headache literature.
In depth
The neuropeptide of pain transmission and neurogenic inflammation. It is why some pain states involve visible swelling with no injury — the nerve itself drives the inflammation.
What drives it
Calm pain signaling increases it.
Calms body-wide inflammation increases it.
Inflammatory sensitization of nociceptive afferents. PMC7005133
What it drives
It increases Calm pain signaling.
Substance P as a nociceptive transmitter in central sensitization. PMC7005133
It increases Neurovascular calm.
In the meninges, substance P contributes to vasodilation, plasma protein extravasation, mast cell degranulation and immune cell recruitment, all of which facilitate neurogenic inflammation and lower the activation threshold of meningeal nociceptors. doi 10.1177/03331024251355944
It reduces Wound healing.
The critical point is a switch, not a level: the transition from an initial inflammatory phase to a proliferative phase is a critical regulatory point that determines wound healing outcomes, and macrophages drive it by switching from pro-inflammatory M1 to anti-inflammatory M2. When proinflammatory M1 macrophages persist without transitioning to anti-inflammatory phenotypes, this contributes to impaired wound healing. Which means anti-inflammatory is not uniformly good here: an ordered and well-controlled inflammatory phase is essential for the normal progression of healing. Suppressing the M1 phase does not accelerate repair - it stalls it. The requirement is timely transition, not less inflammation. Four phases, sequence-critical: hemostasis, inflammation, proliferation, remodeling - for a wound to heal successfully, these four phases must occur in an appropriate sequence and time frame. And an unexpected mechanism worth keeping: disruption of the epithelium generates a directional electrical field, which helps orient keratinocytes for directed migration. doi 10.3390/cells14231850 · PMC8432991
It increases The Third Alarm Bell.
PACAP-38 is co-released with other neuropeptides from activated trigeminal afferents during neurogenic inflammation. doi 10.1093/brain/awn307 · PMC10994530
It increases Trigeminal nerve pathway.
Substance P is released from primary afferent neurons onto neurokinin-1 receptors in the meninges, driving neurogenic inflammation. doi 10.1177/03331024251355944 · PMC5567577
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.