The locus coeruleus noradrenergic system gates deficits in visual attention induced by chronic pain

Abstract

Despite years of research on pain comorbidity with affective disorders and cognitive deficits, it is still unclear how deficit in attention co-occurs with chronic pain. It is likely that altered neuroplasticity and or dysregulated neurotransmitters induced by chronic pain, at which pain and cognitive processing systems overlap, may have a negative effect on cognitive processing such as attention. One of the main common networks involved in attentional and pain processing is the noradrenergic system originating from the locus coeruleus (LC). We hypothesized that heightened noradrenaline release from LC induced by chronic pain could cause a deficit in visual attention. For this purpose, performance on the 5-choice serial reaction time test (5-CSRTT) was tested in animals with and without a chronic constriction injury and a selective depletion of noradrenaline in the LC. In addition, pain sensitivity was measured via mechanical allodynia and thermal hyperalgesia. We found that the increase in pain sensitivity following chronic pain correlates with a decline in executive functions as measured by 5-CSRTT. This was true in conditions of both low and high attentional demand. Interestingly, a selective depletion of noradrenaline in LC improved the attentional deficits caused by chronic pain. We argue that changes to the noradrenergic system originating in LC can improve deficits in visual attention induced by chronic pain. Deficit in attention is a common comorbidity among patients with chronic pain which adversely affects them in their family and work lives. Patients struggle with functional impairment due to pain, and deficite in attention adds to this dysfunction. Our findings identify the NE-LC system as a key mediator between chronic pain and the attentional deficits associated with this. This finding calls for further investigations concerning treatments related to the noradrenergic system to reduce the malicious effects of chronic pain.