Substance P and Its Receptor Are Independently Regulated in the Spinal Cord and Brain | Research

The takeaway

Destroying sensory neurons reduced substance P in the spinal cord without changing its receptor, and dopamine blockade increased substance P in the brain without affecting its receptor either.

Independent regulation
In both spinal cord and basal ganglia, substance P levels changed while NK1 receptor mRNA remained constant

What the researchers found

Capsaicin reduced spinal SP and NKA without changing NK1 receptor mRNA. Haloperidol increased basal ganglia SP mRNA without changing NK1 receptor mRNA.

Why it matters

Understanding that the peptide and its receptor are independently controlled means we cannot assume that changing one automatically changes the other. This is important for designing drugs that target the substance P system.

How the study worked

Neonatal rats received capsaicin to destroy sensory neurons. Adult rats received haloperidol for dopaminergic disruption. SP, NKA, SP mRNA, and NK1 receptor mRNA were measured.

What this study cannot tell us

Animal study in rats with pharmacological and chemical manipulations. Results may not apply to all conditions or species. Only mRNA measured for the receptor.

How to read the evidence

Preliminary — animal study using chemical/pharmacological manipulations to test regulatory relationships. Clear results but limited to specific interventions.

When this study was published

Published in 1992 (34 years ago). NK1 receptor antagonists were subsequently developed as drugs for nausea (aprepitant) and depression.

The bigger picture

This finding matters for drug development: you can't assume that blocking substance P production will also reduce its receptor, or vice versa. Each must be targeted separately for effective therapy in pain and movement disorders.

Questions still open

Are there conditions where the receptor does change in response to peptide levels?
Does this independent regulation hold true in chronic pain or Parkinson's disease?

Common questions

What is substance P?

Substance P is a neuropeptide involved in pain transmission and movement control. It's found in sensory nerves in the spinal cord and in dopamine-related circuits in the brain.

Why does independent regulation matter?

If a disease increases substance P but the receptor stays the same, you need to block the receptor to stop the signal — reducing the peptide alone won't help. This guides which type of drug to develop for conditions involving substance P.

Read the original research

Tachykinin systems in the spinal cord and basal ganglia: influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA.

Journal of neurochemistry, 59(6), 2278-84

View on PubMed ↗

Citation

Sivam, S P; Krause, J E. (1992). Tachykinin systems in the spinal cord and basal ganglia: influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA.. Journal of neurochemistry, 59(6), 2278-84.