No abstract

The Delta6 and Delta5 desaturases and elongases show only very limited activity in marine fish, and little is known of the possibility of enhancing Delta6 desaturase gene expression in these fish. The use of plant oils in marine fish diets is limited by their lack of n-3 highly unsaturated fatty acids (HUFA) despite an abundant content of the 18C fatty acid precursor linoleic and alpha-linolenic acids. The objective of the present study was to determine the ability of larval gilthead seabream to utilize vegetable oils and assess the nutritional regulation of Delta6 desaturase gene expression. Seventeen-day-old gilthead seabream larvae were fed during a 17-day period with one of four different microdiets formulated with either sardine fish oil (FO), soybean, rapeseed or linseed oils, respectively, or a fifth diet containing defatted squid meal and linseed oil. Good larval survival and growth, both in terms of total length and body weight, were obtained by feeding the larvae either rapeseed, soybean or linseed oils. The presence of vegetable oils in the diet increased the levels of 20:2n-9 and 20:2n-6, 18:2n-9, 18:3n-6, 20:3n-6 and 20:4n-6, in larvae fed rapeseed and soybean oils in comparison to those fed FO. In addition, a sixfold increase in the relative expression of Delta6 desaturase-like gene was found in larvae fed rapeseed and soybean oils, denoting the nutritional regulation of desaturase activity through its gene expression in this fish species. However, feeding linseed oil did not increase the expression of the Delta6 desaturase gene to such a high extent.

Pain perception is decreased by shifting attentional focus away from a threatening event. This attentional analgesia engages parallel descending control pathways from anterior cingulate (ACC) to locus coeruleus, and ACC to periaqueductal grey (PAG) - rostral ventromedial medulla (RVM), indicating possible roles for noradrenergic or opioidergic neuromodulators. To determine which pathway modulates nociceptive activity in humans we used simultaneous whole brain-spinal cord pharmacological-fMRI (N=39) across three sessions. Noxious thermal forearm stimulation generated somatotopic-activation of dorsal horn (DH) whose activity correlated with pain report and mirrored attentional pain modulation. Activity in an adjacent cluster reported the interaction between task and noxious stimulus. Effective connectivity analysis revealed that ACC interacts with PAG and RVM to modulate spinal cord activity. Blocking endogenous opioids with Naltrexone impairs attentional analgesia and disrupts RVM-spinal and ACC-PAG connectivity. Noradrenergic augmentation with Reboxetine did not alter attentional analgesia. Cognitive pain modulation involves opioidergic ACC-PAG-RVM descending control which suppresses spinal nociceptive activity.

13Pain perception is diminished when attention is diverted. Our previous human fMRI study, using a 14 2x2 factorial design with thermal stimuli and concurrent visual attention task, linked the brainstem 15 triad of locus coeruleus (LC), rostroventromedial medulla (RVM) and periaqueductal grey (PAG) to 16 attentional analgesia. This study was repeated with a larger cohort, replicating our earlier findings. 17 Pain intensity was encoded by the RVM, whilst activity in the contralateral LC correlated with the 18 magnitude of attentional analgesia. Psycho-Physiological Interaction analysis informed subsequent 19 Dynamic Causal Modelling and identified two parallel paths between forebrain and the brainstem 20 regions involved in analgesia. These cortico-brainstem connections were modulated by attentional 21 demand: a bidirectional anterior cingulate cortex (ACC)right-LC loop, and a top-down influence 22 of task on ACC-PAG-RVM. Under conditions of competing attentional demands the ACC recruits 23 discrete brainstem circuits to modulate nociceptive input. 24 25 Parallel cortical-brainstem pathways to attentional analgesia activation of the ACC-PAG-RVM and/or the ACC-LC system still needs to be demonstrated in 595humans. It is known that both pathways could involve opioids (Fields, 2004) and so previous studies 596 using naloxone do not discriminate between these possibilities. A connectivity analysis examining 597 the network activity between cortical territories, brainstem nuclei and dorsal horn in toto may help to 598 define the key pathway in attentional analgesia. We further postulate that this network may be of 599 importance in chronic conditions where disruption of attention and cognition (i.e. fibromyalgia) are 600 co-morbid alongside pain.