Research Article

Decreased motivation during chronic pain requires long-term depression in the nucleus accumbens

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Science  01 Aug 2014:
Vol. 345, Issue 6196, pp. 535-542
DOI: 10.1126/science.1253994

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A neuropeptide kills patient's motivation

Chronic pain is not only extremely disturbing and unpleasant; it can also make people depressed and demotivated. What causes these effects? Schwartz et al. discovered that chronic pain causes changes in the way a neuropeptide called galanin affects certain neurons in a brain region called the nucleus accumbens (see the Perspective by Fields). Galanin influences a variety of behaviors, including feeding and certain aspects of pain. In this case, it depresses synaptic transmission at specific excitatory synapses. It does so, in part, by changing the ratio of subunits of an important receptor protein.

Science, this issue p. 535; see also p. 513


Several symptoms associated with chronic pain, including fatigue and depression, are characterized by reduced motivation to initiate or complete goal-directed tasks. However, it is unknown whether maladaptive modifications in neural circuits that regulate motivation occur during chronic pain. 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.

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