Substance P

Substance P is a neuropeptide — a short chain of amino acids that functions as both a neurotransmitter and neuromodulator. It is involved primarily in the transmission of pain signals and the regulation of inflammatory responses.

• The “P” stands for Preparation, as it was one of the first peptides isolated from brain and gut tissue in the 1930s.
• It belongs to the tachykinin family of neuropeptides, which act on neurokinin receptors.

🧠 Where Is Substance P Found?

Substance P is widely distributed in the body:

• Central nervous system (CNS) – especially in pain pathways of the spinal cord and brainstem
• Peripheral nervous system – especially sensory neurons
• Immune cells, gastrointestinal tract, and skin

🔬 What Does Substance P Do?

🔹 1. Pain Transmission

• Primary role: Transmits pain signals from peripheral nerves to the spinal cord and brain.
• Released by nociceptive neurons (pain-sensing neurons) in response to injury or inflammation.

🔹 2. Inflammatory Response

• Stimulates histamine release from mast cells
• Causes vasodilation, swelling, and increased vascular permeability
• Promotes recruitment of immune cells to the site of injury

🔹 3. Other Functions

• Affects mood and anxiety
• Plays a role in nausea and vomiting (via the brain’s emetic centers)
• Involved in wound healing
• Modulates respiratory, gastrointestinal, and cardiovascular systems

🎯 How Does It Work?

Substance P primarily binds to the neurokinin-1 receptor (NK1R) on target cells, triggering:

• Calcium influx
• Inflammatory signaling pathways
• Sensitization of pain receptors (hyperalgesia)

📉 What Happens When Substance P Is Blocked?

Drugs that block Substance P (especially NK1 receptor antagonists) can:

• Reduce pain and inflammation
• Treat nausea and vomiting, especially chemotherapy-induced
• Be explored for depression and anxiety treatment (experimental)

Example drug:

• Aprepitant – an NK1 antagonist used to prevent nausea and vomiting in cancer patients

🧪 Summary Table:

🧠 Key Roles of Substance P: