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March 16, 2012


Pain, Itself, Elicits Pain Relief,And Does So Through "Reward" Pathway


Reward Pathway 報酬経路

" Researchers have long known that the body can activate its own form of pain relief in response to painful stimuli. Now, UC San Francisco investigators have determined that, in rats, this long-lasting relief is produced by the brain's "reward" pathway - the neural circuitry activated by drugs of abuse.


In their study, published in the August 15 issue of Journal of Neuroscience, the investigators determined that, at its maximum, the pain relief was as potent as a high dose of morphine.


While various individual structures in the brain have been known to produce analgesia, or pain relief, when electrically stimulated or exposed to narcotic painkillers, the finding provides the first physiological evidence that pain itself elicits analgesia.


narcotic painkillers 麻薬性鎮痛薬

It also provides a surprising twist on the perceived workings of the neural circuitry associated with gratification, said the lead author of the study, Robert W. Gear, PhD, assistant clinical professor of Oral and Maxillofacial Surgery in the NIH Pain Center at UCSF.

さらに、それは、満足に関連した神経回路の知覚された作用上の驚くべきねじれを提供すると、カリフォルニア大学サンフランシスコ校でNIH疼痛センター、口腔顎顔面外科臨床準教授で研究筆頭著者Robert W. Gear, PhDは述べた。

Oral and Maxillofacial Surgery 口腔顎顔面外科

"We're showing that something aversive - exposure to a painful stimulus - as well as exposure to drugs of abuse, stimulate the same reward circuit," said Gear, whose lab is directed by senior author Jon D. Levine, MD, PhD, a professor of Oral and Maxillofacial Surgery and Medicine and director of the NIH Pain Center.

「私たちは次のことを示している、痛い刺激への暴露、同様に薬物乱用への暴露・何か回避的なものは同じ報酬経路を刺激する。」とGear述べた。Gearの研究所は米国国立衛生研究所疼痛センター長で口腔顎顔面外科および医学の教授、筆頭著者Jon D. Levine, MD, PhDによって運営されている。

"Our result casts new light on how to look at the key structure in the reward pathway, the nucleus accumbens, and the role it plays in affirming certain behaviors and thus motivating individuals to act in particular ways," said Gear.


The reward pathway is a neural network in the middle of the brain that prompts good feelings in response to certain behaviors, such as relieving hunger, quenching thirst or having sex, and it thereby reinforces these evolutionarily important drives. However, the circuit also responds to drugs of abuse, such as heroin, cocaine, amphetamine and nicotine, which seem to hijack the circuitry, altering the behavior of its neurons.


アンフェタミン (Amphetamine, Alpha-methylphenethylamine) は合成覚醒剤の一種である。食欲低下や体重抑制、およびナルコレプシーや注意欠陥多動性障害 (ADHD) などの治療に用いられる。能率向上や娯楽目的での濫用は、ほとんどの国で違法とされる。

The nucleus accumbens is the engine of the reward response. And, in their study, the UCSF researchers determined that the reward pathway activates pain relief through the release of both opioids, a morphine-like drug produced by the body, and dopamine, a chemical messenger whose effects can be mimicked by amphetamine and cocaine, in this structure. The finding overturns the long-held assumption that the release of dopamine in the nucleus accumbens is associated only with positive experiences.


nucleus accumbens:側坐核

The evolutionary value of a rush of analgesia is clear, as it could allow, for example, a badly injured individual to escape an attacker. It probably could also explain why some individuals can be injured without persistent pain.


persistent pain持続性疼痛

But the phenomenon may also explain why heroin addicts, in withdrawal, can experience pain or increased sensitivity to painful stimuli. "It may be that one of the reasons people stay addicted is to avoid going through this unpleasant state of withdrawal," said Gear.


heroin addict:ヘロイン中毒者

Under other conditions, it's possible that a painful stimulus, by activating the nucleus accumbens, might itself be experienced as rewarding, as appears to occur in self-injurious behaviors. Interestingly, treatment for this class of disorders, characterized by pursuit of painful experiences often for apparent thrill-seeking value, includes administration of naloxone, a drug that blocks the effects of opioids in this reward circuit.


self-injurious behaviors 自傷行為
naloxone ナロキソン

The researchers conducted the bulk of their study in anesthetized rats, measuring the animals' response to pain signals in the paws. Because these animals were anesthetized, the measurements were taken using a technique known as the jaw-opening reflex, in which the degree to which the jaw opens reflexively in response to painful stimuli to the toothindicates the level of pain experienced. The jaw-opening reflex decreased, a sign of analgesia, as the painful stimulus increased.


jaw-opening reflex 開口反射

The fact that the analgesic effect was demonstrated in the teeth, far from the hindpaw, indicated its general effect in the whole body. The analgesic effects did not require repeated application of the stimuli, and were shown to last at least an hour.


"Our results were quite dramatic," said senior author Levine. "They've spawned several new studies in our lab aimed at revealing more about the role of the reward pathway, and the nucleus accumbens specifically, in human behaviors.








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