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

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.

Adolescent nicotine challenge promotes the future vulnerability to opioid addiction: Involvement of lateral paragigantocellularis neurons.

Tobacco smoking is recognized as a life-threatening risk factor worldwide. Initiation of smoking primarily occurs during adolescence which is a critical developmental phase characterized by specific neurobehavioral alterations. The effect of adolescent nicotine exposure on vulnerability to opioid addiction has not been previously addressed. Furthermore, lateral paragigantocellularis (LPGi) is a key modulator of opiate effects. In this study we investigated the effect of adolescent nicotine treatment on development of morphine tolerance and dependence as well as LPGi neuronal responses to morphine during adulthood. Male Wistar rats received subcutaneous injections of either nicotine or saline during adolescence and then development of morphine tolerance and dependence was assessed during adulthood by tail-flick and withdrawal tests, respectively. In vivo single-unit recording was performed to examine the LPGi neuronal activities. Results indicated that adolescent nicotine exposure significantly facilitates the development of tolerance to analgesic effect of morphine and increases the expression of morphine withdrawal signs in adulthood. Also, it was observed that following adolescent nicotine treatment, the extent of morphine-induced excitation is attenuated in LPGi neurons of adult rats. Moreover, the onset of morphine-induced inhibition was increased in these animals. Neither the baseline, nor the regularity of firing was affected in our observations. It could be concluded that nicotine challenge during adolescence may enhance the future vulnerability to opioid addiction through induction of persistent neuroadaptations in LPGi neurons.