Decreased motivation during chronic pain

results indicate that chronic pain …
interferes with motivated behavior

Decreased motivation during chronic pain requires long-term depression in the nucleus accumbens – Science. 2014 Aug 1; – free full-text PMC article

People with chronic pain know how tiring it is to deal with pain every day all day and I thought this fatigue explained why I have so much trouble getting up off the couch.

This study suggests that our pain triggers changes in the brain that depress the nucleus accumbens core (NAc), which is a key node of the neural circuits mediating motivated behaviors,  

While this relieves some of my guilt, it also frightens me how deeply pain has injected itself into my body, especially my brain.

Several symptoms associated with chronic pain, including fatigue and depression, are characterized by reduced motivation to initiate or complete goal-directed tasks.

Here, we demonstrate that the decreased motivation elicited in mice by two different models of chronic pain requires a galanin receptor 1–triggered depression of excitatory synaptic transmission in indirect pathway nucleus accumbens medium spiny neurons.

These results demonstrate a previously unknown pathological adaption in a key node of motivational neural circuitry that is required for one of the major sequela of chronic pain states and syndromes.

Symptoms that profoundly affect the quality of life of patients with chronic pain include fatigue, reductions in pre-pain activities, and depression.

A common feature of these symptoms is a decrease in the motivation to undertake and to successfully complete goal-directed actions.

Although in the setting of acute pain these features may be adaptive by limiting activity during the healing process and reducing the likelihood of future injury by motivating avoidance, they are a major source of the morbidity accompanying chronic pain syndromes.

Here, we hypothesize that like the maladaptive neural plasticity that contributes to somatosensory symptoms of chronic pain, concurrent maladaptive plasticity occurs in neural circuits that regulate motivation

Therefore, we focused on the nucleus accumbens core (NAc) because it is a key node of the neural circuits mediating motivated behaviors, and activity within the human NAc correlates with both the subjective experience of pain as well as the transition to chronic pain

Chronic pain reduces motivation in two mouse models

We used two mouse models of chronic pain; chronic inflammatory pain and neuropathic pain.

Before inducing the models, all animals made a similar number of nose pokes and earned a comparable number of rewards

In contrast, 7 to 21 days after induction of chronic pain, animals exhibited a ~40% drop in the number of nose pokes to earn rewards, resulting in a stable reduction in the rewards earned over the 3-week testing period

Chronic pain elicits synaptic modifications in nucleus accumbens



The NAc is a key node of the neural circuitry that regulates motivation

Manipulations that disrupt its activity appear to impair performance on more difficult operant tasks but have little effect on the performance of easy operant tasks, perhaps because impairments of NAc function bias behavioral choices to those that require less effort

Here, we demonstrate that two different chronic pain models cause a selective impairment in performance on a difficult PR task but have no detectable effects on easier tasks or the value of rewards.

This chronic pain–induced decrease in motivation requires a decreased excitatory drive onto indirect pathway NAc MSNs downstream of activation of the neuropeptide receptor GalR1 via a cascade of synaptic modifications

Nonetheless, the present findings support a key role of NAc D2-MSNs in regulating performance during more difficult tasks.

Because the NAc integrates inputs from multiple structures, future studies will need to address the critical question of whether the chronic pain–induced synaptic changes are global, affecting all excitatory inputs onto MSNs, or rather are input-specific.

Previous studies on mouse models of chronic pain report no change in home cage behaviors or measures of affective behaviors during the first month of the pathology.

Within a similar time frame, by focusing on a more subtle aspect of goal-directed operant behavior—the motivation to work for natural reward—we found that motivation was impaired.

Our results suggest that pain-induced synaptic adaptations within the NAc contribute to a subjective impairment in the ability to initiate or sustain physical or mental tasks, or to the symptom of central fatigue commonly reported by chronic pain patients.

These results also suggest specific synaptic targets that may be susceptible to therapeutic interventions.  .


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