In 1931, two scientists – Ulf von Euler and John Gaddum – described something they called Substance P.
The P in Substance P stands for preparation – as in something prepared in a laboratory. The generic name was used originally to designate the active agent in a particular preparation of tissue extracts and stuck. Substance P didn’t seem to have any clearly-definable biological role.
Von Euler was a Swedish physiologist and pharmacologist who shared the Nobel Prize in Physiology or Medicine in 1970 for his work on neurotransmitters. Gaddum was a founding member of the British Pharmacological Society and the first editor of the British Journal of Pharmacology. (In an interesting side note, Gaddum played around with LSD and then explained how it causes mental disturbances by blocking the stimulating effects of serotonin.)
Von Euler and Gaddam found that brain and intestine tissues contained a substance that stimulated contraction of the isolated rabbit jejunum (the second part of the small intestine), and caused transient hypotension (a temporary drop in blood pressure) when injected intravenously into anesthetized rabbits.
Substance P (SP) is a peptide. Peptides (from a Greek word meaning “digested”) are short chains of amino acids linked by peptide (amide) bonds. A polypeptide (poly means “many”) is a long, continuous, and unbranched peptide chain. Both proteins and peptides are made up of polypeptides. By convention, peptides contain about 50 or fewer amino acids while proteins have more than 50 amino acids.
Specifically, SP is a small undecapeptide (which means it is composed of a chain of 11 amino acid residues). It is released from the terminals of certain sensory nerves. The sensory function of SP is thought to be linked to the transmission of pain information into the central nervous system (CNS).
Tests revealed that SP is widely but selectively distributed in both the central and peripheral nervous systems and is found in fiber tracts and nerve endings. It was classified as a different kind of neurotransmitter, an electro-chemical that communicates signals from one brain cell to another.
Scientists discovered that when the function of SP is genetically disrupted in mice, the animals show reduced responses to painful stimuli. The concluded that SP is important for coordinating an animal’s response to major stressors such as pain, injury or invasion of territory.
Chemicals that inhibit SP receptors in the body might, therefore, be useful in treating stress-related diseases as well as an analgesic (pain reliever) for people with nervous disorders ranging from PTSD to fibromyalgia.
SP is secreted by nerves and inflammatory cells when the CNS is stimulated. It plays a part in regulating the pain threshold, the point at which the mind perceives sensation as pain. Increased levels of SP can make nerves more sensitive to pain and elevate a person’s awareness of pain. Patients with asthma are hyperresponsive to SP.
High amounts of SP in the body contribute to “turning up the volume” on feeling pain. The substance participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems.
In cases of fibromyalgia, SP is one of several neurotransmitters thought to be imbalanced, leading to a heightened sensation of pain.
SP regulates smooth muscle contractions and immune function in the gastrointestinal tract. Elevated levels of SP have been detected in the rectum and colon of patients with inflammatory bowel disease as well as in the synovial joint fluid and serum of patients with rheumatoid arthritis.
By lowering levels of SP in the body, we can “dial back” our personal perception of pain. The good news is that there are SP-fighting products available today in most pharmacies.
Resinous and pungent capsaicin (cap-SAY-sin) is the active ingredient in chili peppers that makes them hot. Added to therapeutic lotions and creams, capsaicin has been proven effective in easing muscle and joint pain.
Topical application of capsaicin directly on the skin relieves pain and itching by acting on sensory nerves. Used regularly, capsaicin topicals don’t actually deplete the amount of substance P in the body but they do reduce skin hypersensitivity and knocks out sensory neurons called nociceptors.
Nociceptors respond to damaging or potentially-damaging stimuli by sending “possible threat” signals to the spinal cord and the brain. The brain produces the sensation of pain if it perceives the threat as credible to direct attention to the afflicted body part so the threat can be avoided or made less harmful.
In one study, a single 60-min application of a highly concentrated capsaicin 8% patch (Qutenza™), which was recently approved in Europe and the U.S., produced effective pain relief for up to 12 weeks in patients with neuropathic pain.
Advantages of the high-concentration capsaicin patch include longer duration of effect and low risk of side effects or undesirable drug-to-drug interactions.
Over-the-counter remedies containing capsaicin are readily available. Stronger concentrations require a doctor’s prescription. Be aware that capsaicin can create a burning sensation that passes with repeated use. Read and follow all recommendations and directions when handling capsaicin products.
Treating burning pain with a burning medication may seem counterintuitive but folk medicine has often held this to be true. The first formal report touting the pain-reducing properties of topical capsaicin in the West was published in 1850 and recommended using an alcoholic hot pepper extract to treat burning or itching extremities.