Study identifies new drug target for chronic, touch-evoked pain

March 10, 2014 by Ranjini Raghunath

(Medical Xpress)—Researchers at the School of Medicine have identified a subset of nerve cells that mediates a form of chronic, touch-evoked pain called tactile allodynia, a condition that is resistant to conventional pain medication.

The discovery could point researchers to more fruitful efforts to develop effective drugs for the condition.

Touch-evoked pain occurs as part of a larger condition arising from damage or disruption of nerve-cell circuits or signals caused by disorders such as alcoholism, diabetes, shingles and AIDS, or procedures such as spine surgery and chemotherapy. For patients with tactile allodynia, the slightest touch—a gentle caress or the brush of shirt against skin—can cause excruciating pain because changes in nerve-cell signals or networks trick the brain into mistaking touch for pain.

The study, published online Feb. 27 in Neuron, found that these "touch" neurons are different from the usual "pain" neurons that respond to stimuli such as cuts or bruises.

Unlike pain caused by such wounds, neuropathic pain is difficult to manage because little can be done to repair nerve damage. Managing it may require strong painkillers or combinations of treatments.

Common painkillers such as have little effect on touch-evoked pain, possibly because they don't target the touch neurons, the authors say. Morphine binds to specific protein-binding sites on pain neurons called mu , or MORs, and cuts off the their signals so that the brain can no longer sense pain.

However, the touch neurons do not carry MORs, which is why morphine cannot bind to them and block the pain. Instead, they carry delta opioid receptors, or DORs, whose role in pain control has been unclear until recently.

"That's been the problem so far; any type of you have, you go into the clinic and very likely you will be treated with morphine-like opioids," said Gregory Scherrer, PharmD, PhD, the senior author of the study and an assistant professor of anesthesia. "You can give some of these patients as much morphine as you want; it won't work if the mu opioid receptor is not present on the neurons that underlie that type of pain."

There are currently no Food and Drug Administration-approved pain-control drugs that target DORs. Previous attempts at developing DOR-targeting drugs haven't succeeded because researchers didn't know what type of pain such drugs would be useful for, Scherrer said.

Two DOR-binding drugs developed for by Adolor Corp., a biotechnology firm, for instance, probably failed because there is no compelling evidence that DOR was present or involved. AstraZeneca, another pharmaceutical firm, also had a DOR program but recently stopped its research efforts, Scherrer added.

"Now that we have provided a rationale and mechanism supporting the utility of DOR agonists for cutaneous pain and tactile allodynia, these companies will be able to design trials more carefully to evaluate specifically the drugs' efficacy against touch-evoked pain," he said.

Earlier studies by Scherrer and others hinted at the presence of special nerve fibers on the skin that might contribute to touch-evoked pain.

In the current study, Scherrer and colleagues used fluorescent mouse models to isolate these neurons and identify how they control touch-evoked pain. They found that DOR can play an inhibitory role in these neurons: When proteins bind to DOR, they cut off communication to the spinal cord, through which sensory signals travel to the brain.

DOR-carrying "touch" neurons pervade the skin and could easily be targeted by drugs in the form of skin patches or topical creams, Scherrer suggested.

"By contrast, most MOR-carrying neurons penetrate internal organs," he said. "That's why morphine is effective in treating post-surgery pain, for example."

Scherrer and fellow researchers tested two different DOR-binding compounds individually on mice and found that both reduced the mice's sensitivity to touch-evoked pain.

Preliminary studies also indicate that DOR-targeting drugs might not cause dramatic side effects like morphine does, especially if they can be used topically, Scherrer said.

"Morphine and other MOR-targeting drugs have myriad deleterious side effects—including addiction, respiratory depression, constipation, nausea and vomiting—that further limits their utility for ," he said.

The next step is to determine whether DOR could be a target for other types of pain, such as , pain from bone cancer and , Scherrer added.

The findings also suggest that the body's opioid system—normally associated with and addiction—may also respond to other stimuli such as touch.

"We may have underestimated the importance of the opioid system and what can be achieved with drugs targeting other subtypes of opioid receptors," Scherrer said.

Explore further: Opioid tolerance and pain hypersensitivity associated with mTOR activation

Related Stories

Opioid tolerance and pain hypersensitivity associated with mTOR activation

January 2, 2014
Currently, opioids are the standard treatment for chronic pain. Patients on opioids for long periods of time become desensitized to these drugs or become paradoxically hypersensitive to pain (hyperalgesia); however, the adaptive ...

Opioid abuse initiates specific protein interactions in neurons in brain's reward system

February 24, 2014
Identifying the specific pathways that promote opioid addiction, pain relief, and tolerance are crucial for developing more effective and less dangerous analgesics, as well as developing new treatments for addiction. Now, ...

Using morphine after abdominal surgery may prolong pain, researchers find

November 12, 2013
Using morphine to fight the pain associated with abdominal surgery may paradoxically prolong a patient's suffering, doubling or even tripling the amount of time it takes to recover from the surgical pain, according to researchers ...

A path to lower-risk painkillers

June 10, 2013
For patients managing cancer and other chronic health issues, painkillers such as morphine and Vicodin are often essential for pain relief. The body's natural tendency to develop tolerance to these medications, however, often ...

Codeine could increase users' sensitivity to pain

September 12, 2013
Using large and frequent doses of the pain-killer codeine may actually produce heightened sensitivity to pain, without the same level of relief offered by morphine, according to new research from the University of Adelaide.

Researcher finds method to improve morphine's effect on managing pain

October 4, 2013
A method to prevent the body from developing tolerance to morphine, a powerful and commonly used pain medication, has been discovered by a Georgia State University researcher.

Recommended for you

Scientists discover combined sensory map for heat, humidity in fly brain

July 20, 2017
Northwestern University neuroscientists now can visualize how fruit flies sense and process humidity and temperature together through a "sensory map" within their brains, according to new research.

Faulty support cells disrupt communication in brains of people with schizophrenia

July 20, 2017
New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia. When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia ...

Scientists reveal how patterns of brain activity direct specific body movements

July 20, 2017
New research by Columbia scientists offers fresh insight into how the brain tells the body to move, from simple behaviors like walking, to trained movements that may take years to master. The discovery in mice advances knowledge ...

Team traces masculinization in mice to estrogen receptor in inhibitory neurons

July 20, 2017
Researchers at Cold Spring Harbor Laboratory (CSHL) have opened a black box in the brain whose contents explain one of the remarkable yet mysterious facts of life.

Speech language therapy delivered through the Internet leads to similar improvements as in-person treatment

July 20, 2017
Telerehabilitation helps healthcare professionals reach more patients in need, but some worry it doesn't offer the same quality of care as in-person treatment. This isn't the case, according to recent research by Baycrest.

New study reveals contrasts in how groups of neurons function during decision making

July 19, 2017
By training mice to perform a sound identification task in a virtual reality maze, researchers at Harvard Medical School and the Istituto Italiano di Tecnologia (IIT) have identified striking contrasts in how groups of neurons ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.