Research May Pave The Way To Understanding And Controlling Chronic Pain

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Research May Pave The Way To Understanding And Controlling Chronic Pain

http://www.medicalnewstoday.com/articles/218639.php

Researchers at the University of California, have discovered a

" cross-talk " between two major biological pathways that involve pain - research

that may pave the way to new approaches to understanding and controlling chronic

pain.

And they did it with something old, new, practical and basic.

The newly published research reveals that analgesia mediated by inhibitors of

the enzyme, soluble epoxide hydrolase (sEH), is dependent on a pain-mediating

second messenger known as cyclic adenosinemonophosphate or cAMP.

" The interaction of many complex biological pathways is essential for the

development of persistent pain, whether inflammatory or neuropathic, " said lead

researcher Bora Inceoglou of the Bruce Hammock lab, UC Department of

Entomology. Inflammatory pain includes arthritis, and neuropathic pain is linked

to diabetes and other diseases, and trauma.

" Pain is a major health concern and painkiller medications or analgesics do

different things, " Inceoglu said. Painkilling medications may target the pain,

but have side effects or lack a broad-spectrum efficacy.

The collaborative study, the work of scientists in the UC Department of

Entomology, UC Cancer Center, UC School of Medicine and the School

of Veterinary Medicine, is published in the March 7th early edition of the

Proceedings of the National Academy of Sciences (PNAS).

An estimated 9 percent or 30 million adults in the United States suffer from

moderate to severe non-cancer related chronic pain, according to the American

Pain Society.

The messenger, cAMP, relays responses and mediates the action of many biological

processes, including inflammation, and cardiac and smooth muscle contraction.

The research, done on rodents and funded by the National Institutes of Health,

confirmed earlier studies at UC that showed stabilization of natural

epoxy-fatty acids (EFAs) through inhibition of sEH reduces pain. " However, in

the absence of an underlying painful state, inhibition of sEH is ineffective, "

Inceoglu said.

" This permits normal pain responses that serve to protect us from tissue damage

to remain intact, while alleviating debilitating pain, " said co-author and pain

neurobiologist Jinks, associate professor of anesthesiology and pain

medicine, UC School of Medicine.

" Another advantage of inhibition of sEH is that it does not impair motor skills

in several tests, unlike other analgesics, " said graduate student researcher

Wagner of the Hammock lab research team.

While conducting the research, the scientists found something they weren't

looking for. " To our surprise, we found that cAMP interacts with natural EFAs

and regulates the analgesic or pain activity of sEH inhibitors, " Inceoglu said.

" This demonstrates the power of using advance instrumental analysis techniques

to better understand the molecular mechanism of biological effects, " said Nils

Helge Schebb, a postdoctoral researcher from the Hammock group who worked on the

quantification of the oxylipins in this project. Schebb leaves UC this

week to accept a position as junior research group leader at the University of

Veterinary Medicine, Hannover, Germany.

" This is like something old, something new, something practical and something

basic, too, " said Hammock, a distinguished professor of entomology who holds a

joint appointment with the UC Cancer Research Center.

Old? The research, Hammock said, involves " an old class of drugs known as

phosphodiesterase inhibitors that likely exert part of their action by

increasing the levels of natural compounds in the body called EETs

(epoxyeicosatrienoic acids). Rolipram, Viagra, Theophyline, and Ibudilast are

all in the phosphodiesterase-inhibitor class. "

New? The Hammock lab previously reported that a new class of experimental drugs

called soluble epoxide hydrolase inhibitors (sEHIs) stabilize and also increase

EETs.

Practical and basic? " A practical application of this work demonstrated by Bora

Inceoglu is that the combination of this old and new class of drugs are highly

effective in controlling pain, " said Hammock, senior author of the paper. " Of

course, the basic aspects of the work include new insights in how EETs, cyclic

nucleotides and the enzymes that degrade them interact to regulate a variety of

biological functions. "

Both the old and the new class of drugs are based on inhibiting enzymes which

degrade potent natural chemical mediators.

Inceoglu, Hammock, Jinks, Schebb, and Wagner co-authored the paper with

veterinary anesthesiologist Brosnan, associate professor of surgical and

radiological sciences, School of Veterinary Medicine; and Christophe Morisseau,

Arzu Ulu, Hegedus and Tristan Rose, Department of Entomology and the

Cancer Center.

The Jinks lab played a major role in the earlier UC studies that showed a

stabilization of EFAs through inhibition of sHE reduces pain. The Hammock lab

works closely with the Jinks lab.

The pain discovery would not have been possible without sophisticated mass

spectrometry equipment which allowed the analysis of the vanishingly small

amounts of natural compounds that control pain and inflammation in the body, the

researchers agreed.

Hammock described the potential practical applications of these fundamental

discoveries as exciting. " We all have both suffered pain and have friends with

unrelenting chronic pain problems, " he said. " The possibility of combining

members of an old class of drugs with our new sEHI and actually providing relief

for pain is very exciting. "

Notes:

From his time as a graduate student, Hammock and his laboratory have focused on

xenobiotic metabolism and largely on esterases and epoxide hydrolases. Current

projects involve examining the role of esterases in insecticide resistance and

human metabolism of pyrethroids. His laboratory is exploiting inhibitors of

epoxide hydrolases as drugs to treat diabetes, inflammation, ischemia, and

cardiovascular disease.

Source: University of California - Health System