Impairment Of Motivational Behavior Associated With Chronic Pain:The Role Of Communication Between MPFC And NAc

In chronic pain conditions,persistent pain and its comorbidities continuously bother the patients and put enormous burden on their work and daily life.Chronic paininduced depression and fatigue were found to be closely associated with the decline in motivation in patients.Recent studies have revealed abnormality in brain circuits related to reward and motivation in chronic pain conditions.However,which cortical and subcortical areas play critical roles in pain-induced motivational impairment remains unclear.In the present study,we explored the neural mechanism underlying motivational impairment induced by chronic pain,by examining changes of neural activities in the motivation-related neural circuitry in an animal model of neuropathic pain.Experiments were performed in the neuropathic rats with sural-spared sciatic nerve injury(SNI).The behavioral performance was investigated using an operant effort-based decision-making paradigm in which animals could choose either to obtain a large reward by climbing a higher barrier(high effort/high reward)or to select another option with a small reward(low effort/low reward).Compared with the sham rats,the SNI rats with chronic pain showed a reduced rate of choosing the high effort/high reward arm 2~4 weeks after the SNI surgery.However,the rats with acute pain induced by intradermally injected capsaicin did not exhibit such a decline in the high effort/high reward arm choice,indicating that the sensory component of pain is not the direct cause of declined motivation.These results demonstrated that rats with neuropathic pain developed deficit in motivation and reward-based decision-making.To explore the underlying mechanism,we simultaneously recorded neural activity in the medial prefrontal cortex(mPFC)and nucleus accumbens(NAc)while the rats were performing the effort-based decision-making task.We found that 1)the theta-band(4-8Hz)power of the local field potential(LFP)in the mPFC was correlated with the number of high effort/high reward choices;2)compared with the sham rats,the SNI rats showed significantly lower theta-band power of the LFP in the mPFC and lower gamma-band(55-75Hz)power in the NAc during the decision-making task;and 3)both the coherence of theta-frequency oscillation between the mPFC and the NAc and the coupling of mPFC theta phase-NAc gamma amplitude decreased in the SNI rats compared with the sham group.These electrophysiological results suggested that the alteration of neural activities in the mPFC and NAc and the attenuation of the communication between these two areas may serve as the neural mechanism for the impaired performance in motivational decision making in chronic pain conditions.In line with this postulation,further experiments demonstrated that optogenetical deactivation of terminals projected from the mPFC to the NAc also caused a decrease of the high effort/high reward choices in the sham rats.In summary,the present study demonstrates the association between the behavioral impairment of motivational decision making and neuroplasticity in the motivation/ reward neural circuitry occurred in the chronic pain conditions.We postulate that the functional disturbances in the mPFC-NAc circuit likely contribute to the motivational deficits associated with chronic pain.Our findings provide important information for the understanding of the neural basis for the association between the declined motivation and chronic pain.