Substance P is a polypeptide that works both as a neuromodulator and as a neurotransmitter. It is one of the substances most involved in the transmission of pain. This neuropeptide has the characteristic of binding to specific NK1 receptors located on neurons. Let’s discover this substance full of complexity.

The letter “P” is a derivative of the English word “pain” which indicates pain. Pain is an unpleasant feeling, which can be of a physical or psychological nature. The pain forms in the central nervous system and places a synaptic link in the spinal cord.

A neurotransmitter is a chemical messenger that transmits messages from one neuron to another, at synapses. Two excitatory neurotransmitters, including substance P, have been separated and made responsible for the transmission of the nociceptive message between the presynaptic neuron and the postsynaptic neuron.

These two neurotransmitters allow the spread of the painful nerve message to the brain and thus allow the pain to become “real”. These two neurotransmitters attach themselves to the postsynaptic neuron. Substance P is therefore a neuropeptide, that is to say a peptide secreted by a neuron and having a neuromodulator function, consisting of eleven amino acids belonging to the tachykinin family or neurokinins (NK).

Substance P is widely distributed throughout the body, both to the central nervous system (the brain and spinal cord), and to the peripheral nervous system (all other nerves and nerve cells). The greatest concentration is found in the Niger locus, the hypothalamus and the pineal gland.

Substance P seems to be among the substances most involved in the transmission of pain. In the event of a painful stimulus, substance P is released by the endings of the nociceptive fibers and will bind to specific receptors called NK1, which will trigger neurons in the posterior horn of the spinal cord.

In the central nervous system, substance P is responsible for the regulation of mood disorders, fear, respiratory rate, and pain.

In addition, through a phenomenon called the axon reflex, substance P is an extremely effective vasodilator because it allows substances such as bradykinin, l histamine and serotonin.

Finally, the activation of substance P causes the vomiting reflex: in fact, the vomiting centers, located in the brainstem, contain high concentrations of substance P. Their activation in addition to other neurotransmitters such as choline, l histamine, dopamine, serotonin stimulates the vomiting reflex.

It also plays a role in inflammation and in sleep phenomena. Morphine drugs are inhibitors of substance P.

Fibromyalgia is a syndrome characterized by pain that spreads throughout the body, pain associated with too much fatigue and sleep disturbances. This syndrome does not form serious complications, but often penalizes the sufferer from carrying out daily activities or giving a full-time job.

It seems that a deficiency of certain neurotransmitters such as substance P is linked. In fact, the excess of substance P causes hyperalgesia by reducing the pain inhibiting systems. In other words, a substance P metabolic disorder would increase pain receptivity.

Substance P has various effects:

• It causes vasodilation: in intravenous injection, substance P causes very significant vasodilation, and after intradermal injection, it causes redness and pain resembling that given by histamine;
• It modifies certain secretions: increased salivary secretion, decreased insulin secretion, increased histamine release;
• Substance P could be implicated in certain mental disorders such as depressive states. ;
• Substance P, when injected, causes nausea and vomiting.

An antiemetic, a substance P NK1 receptor antagonist, is marketed for the prevention of nausea and vomiting due to emetogenic chemotherapy.

It is a strong vasodilator which can induce a release of bradykinin, histamine and serotonin.

Substance P has been shown to stimulate cell growth in cell culture and to aid in the healing of “dragging” ulcers in some patients.