Association between Chronic Pain and Alterations in the Mesolimbic Dopaminergic System

pattismith

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Association between Chronic Pain and Alterations in the Mesolimbic Dopaminergic System


oct 2020


Seoyon Yang
1, Mathieu Boudier-Revéret 2, Yoo Jin Choo 3, Min Cheol Chang 4

Free PMC article
Abstract

Chronic pain (pain lasting for >3 months) decreases patient quality of life and even occupational abilities. It can be controlled by treatment, but often persists even after management.

To properly control pain, its underlying mechanisms must be determined.

This review outlines the role of the mesolimbic dopaminergic system in chronic pain.

The mesolimbic system, a neural circuit, delivers dopamine from the ventral tegmental area to neural structures such as the nucleus accumbens, prefrontal cortex, anterior cingulate cortex, and amygdala. It controls executive, affective, and motivational functions.

Chronic pain patients suffer from low dopamine production and delivery in this system.

The volumes of structures constituting the mesolimbic system are known to be decreased in such patients.

Studies on administration of dopaminergic drugs to control chronic pain, with a focus on increasing low dopamine levels in the mesolimbic system, show that it is effective in patients with Parkinson's disease, restless legs syndrome, fibromyalgia, dry mouth syndrome, lumbar radicular pain, and chronic back pain.

However, very few studies have confirmed these effects, and dopaminergic drugs are not commonly used to treat the various diseases causing chronic pain.

Thus, further studies are required to determine the effectiveness of such treatment for chronic pain.


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xebex

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Yes I tried modafinil too and it was helpful for motivations but not pain and not as helpful as Ritalin - I couldn’t get out of bed the next day I think it did something to my acetylcholine receptors because I get the same day after hangover/extreme sleepiness from mestinon and Benadryl. Ritalin was the lesser of the 3 in side effects/hangover/ rebound.
 

pattismith

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This 2018 study found the same link between hyperalgesia and an altered mesolimbic dopamine circuit.




Activation of ventral tegmental area dopaminergic neurons reverses pathological allodynia resulting from nerve injury or bone cancer
Moe Watanabe 1, Michiko Narita 1, Yusuke Hamada 1, Akira Yamashita 1, Hideki Tamura 2, Daigo Ikegami 1 3, Takashige Kondo 1, Tatsuto Shinzato 1, Takatsune Shimizu 4, Yumi Fukuchi 4, Akihiro Muto 4, Hideyuki Okano 2 5, Akihiro Yamanaka 6, Vivianne L Tawfik 7, Naoko Kuzumaki 1, Edita Navratilova 3, Frank Porreca 3, Minoru Narita 1 2
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Free PMC article

Abstract

Chronic pain induced by nerve damage due to trauma or invasion of cancer to the bone elicits severe ongoing pain as well as hyperalgesia and allodynia likely reflecting adaptive changes within central circuits that amplify nociceptive signals.

The present study explored the possible contribution of the mesolimbic dopaminergic circuit in promoting allodynia related to neuropathic and cancer pain.

Mice with ligation of the sciatic nerve or treated with intrafemoral osteosarcoma cells showed allodynia to a thermal stimulus applied to the paw on the injured side.

Patch clamp electrophysiology revealed that the intrinsic neuronal excitability of ventral tegmental area (VTA) dopamine neurons projecting to the nucleus accumbens (N.Acc.) was significantly reduced in those mice.

We used tyrosine hydroxylase (TH)-cre mice that were microinjected with adeno-associated virus (AAV) to express channelrhodopsin-2 (ChR2) to allow optogenetic stimulation of VTA dopaminergic neurons in the VTA or in their N.Acc. terminals.

Optogenetic activation of these cells produced a significant but transient anti-allodynic effect in nerve injured or tumor-bearing mice without increasing response thresholds to thermal stimulation in sham-operated animals.

Suppressed activity of mesolimbic dopaminergic neurons is likely to contribute to decreased inhibition of N.Acc. output neurons and to neuropathic or cancer pain-induced allodynia suggesting strategies for modulation of pathological pain states.