Peptides Implicated In Body's Response To Pain

March 25, 1998

Pain is an extremely disabling condition leading to an annual cost of $65 billion lost in work productivity and 4 billion work days. It also accounts for 40 million visits per year to physicians for "new" pain and $3 billion in sales each year of over-the-counter analgesics. Scientists studying animal models with support from the National Institutes of Health have found that a chemical, called neurokinin A, may be responsible for the body's response to moderate-to-intense pain. This finding, reported in the March 26, 1998, issue of Nature(1), may eventually lead to new treatments for pain.

Under the leadership of Allan I. Basbaum, Ph.D., neuroscientists at the University of California at San Francisco (UCSF) and the University of Minnesota have found that mice with a mutation in a gene that encodes for two chemicals, peptides called substance P and neurokinin A, have a reduced response to increased pain stimuli.

The experiment suggests that these peptides play a role in the body's pain responses and are essential components in the production of moderate-to-severe pain.

"After seeing this change, we now believe that substance P and neurokinin A must work in combination to account for pain responses in the body," said Dr. Basbaum, Chair of the Department of Anatomy and Physiology and the Division of Neuroscience at UCSF.

The scientists interrupted the gene encoding for preprotachykinin, whose peptide products include substance P, long believed to play an important role in pain response, and neurokinin A. They observed that the colony of mutant animals maintained the same response to mild pain as their non-mutant mouse counterparts. The mutant mice, however, exhibited a reduced response when subjected to stimuli producing moderate-to-intense pain. Scientists believe that neurokinin A, along with substance P, is released directly in response to intensified pain stimuli.

The study authors received funding from several institutes at the National Institutes of Health, including the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Dental Research, and the National Institute on Drug Abuse. Additional support came from the Howard Hughes Medical Institute.

"Although pain can in most cases be effectively treated, it is still a major health problem. More than 50 million Americans are partially or totally disabled by pain, from the occasional migraine headache to chronic back pain to the pain that accompanies diseases such as cancer," says NINDS Acting Director Audrey S. Penn, M.D. "There is a pressing need for more compounds in the arsenal of pain medications available to physicians and patients. This study puts us one step closer to correcting this very serious problem."

Certain chemicals, glutamate, for example, act in the transmission of pain messages by stimulating pain receptors. It has been previously demonstrated that when glutamate receptors are blocked, experimental mice exhibit a reduction in their responses to pain, providing scientists with compelling evidence of the chemical's role in transmission of pain messages.

Together with glutamate, substance P is known to stimulate pain receptors, but its precise action is less clear and its function complex. In the current study, release of substance P and neurokinin A causes inflammation and a pain response that is markedly reduced in the mutant mouse colony. Release of neurokinin A, the scientists believe, is required to produce moderate-to-intense pain.

Neurokinin A is a tachykinin, a type of peptide belonging to a family of chemicals known as kinins. Kinins play a role in inflammation and, in the case of pain, are thought to stimulate pain receptors in the body.

The study authors believe that drugs involved with the release of neurokinin A, called neurokinin antagonists, might one day be used in combination with morphine as a treatment for moderate-to-severe pain.

"There are many factors present in pain perception," says Cheryl Kitt, Ph.D., a health scientist administrator at the NINDS. "This research is a first step in looking at the role of tachykinins in moderate-to-intense pain. Although the findings have great potential for the development of new drugs for treating pain, we still need to investigate the roles of other factors, such as additional kinin genes."

"These results, if demonstrated in clinical studies, might result in a combination of neurokinin A antagonists and morphine for the treatment of moderate to intense pain. Such a treatment would have fewer side effects and would enable lower doses of morphine to be used," said Dr. Basbaum.

The NINDS, one of the National Institutes of Health located in Bethesda, Maryland, is the nation's leading supporter of research on the brain and nervous system and a lead agency for the Congressionally designated Decade of the Brain. The Institute is also one of 21 NIH components participating in the recently-established NIH Pain Research Consortium.

(1) Cao, Y.Q., Mantyh, P.W., Carlson, E.J., Gillespie, A.M., Epstein, C.J., Basbaum, A.I. Primary Afferent Tachykinins are Required to Experience Moderate to Intense Pain. Nature, Vol. 392, March 26, 1998, P. 390-394.
This release will be available on the World Wide Web at

NIH/National Institute of Neurological Disorders and Stroke

Related Pain Articles from Brightsurf:

Pain researchers get a common language to describe pain
Pain researchers around the world have agreed to classify pain in the mouth, jaw and face according to the same system.

It's not just a pain in the head -- facial pain can be a symptom of headaches too
A new study finds that up to 10% of people with headaches also have facial pain.

New opioid speeds up recovery without increasing pain sensitivity or risk of chronic pain
A new type of non-addictive opioid developed by researchers at Tulane University and the Southeast Louisiana Veterans Health Care System accelerates recovery time from pain compared to morphine without increasing pain sensitivity, according to a new study published in the Journal of Neuroinflammation.

The insular cortex processes pain and drives learning from pain
Neuroscientists at EPFL have discovered an area of the brain, the insular cortex, that processes painful experiences and thereby drives learning from aversive events.

Pain, pain go away: new tools improve students' experience of school-based vaccines
Researchers at the University of Toronto and The Hospital for Sick Children (SickKids) have teamed up with educators, public health practitioners and grade seven students in Ontario to develop and implement a new approach to delivering school-based vaccines that improves student experience.

Pain sensitization increases risk of persistent knee pain
Becoming more sensitive to pain, or pain sensitization, is an important risk factor for developing persistent knee pain in osteoarthritis (OA), according to a new study by researchers from the Université de Montréal (UdeM) School of Rehabilitation and Hôpital Maisonneuve Rosemont Research Centre (CRHMR) in collaboration with researchers at Boston University School of Medicine (BUSM).

Becoming more sensitive to pain increases the risk of knee pain not going away
A new study by researchers in Montreal and Boston looks at the role that pain plays in osteoarthritis, a disease that affects over 300 million adults worldwide.

Pain disruption therapy treats source of chronic back pain
People with treatment-resistant back pain may get significant and lasting relief with dorsal root ganglion (DRG) stimulation therapy, an innovative treatment that short-circuits pain, suggests a study presented at the ANESTHESIOLOGY® 2018 annual meeting.

Sugar pills relieve pain for chronic pain patients
Someday doctors may prescribe sugar pills for certain chronic pain patients based on their brain anatomy and psychology.

Peripheral nerve block provides some with long-lasting pain relief for severe facial pain
A new study has shown that use of peripheral nerve blocks in the treatment of Trigeminal Neuralgia (TGN) may produce long-term pain relief.

Read More: Pain News and Pain Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to