net OR submit four copies of the application, in English, by regular mail only to: The Trustees, The H.J. Eysenck Memorial Fund, PO Box 27824, London SE24 0WE Applications must be received by the 31st January 2014 and the successful candidate will be notified by the 1st May 2014. “
“Descending modulation from brainstem areas of spinal nociceptive transmission is a well-documented phenomenon. Most early studies describe a role for descending inhibitory control of spinal nociceptive activity mediated primarily by noradrenergic and serotonergic (5-HT) pathways,
but more recently, the role of descending facilitation from the brainstem, onto spinal nociceptive pathways, has stimulated intense research and, in particular, the role for 5-HT in
mediating this excitatory drive (Bannister et al., 2009 and Wei INCB018424 manufacturer et al., 2010). Serotonergic input to the dorsal horn of the spinal cord derives almost entirely from supraspinal sources, with a minor contribution from local spinal neurones. 5-HT pathways, running directly from the rostral ventromedial medulla (RVM; the site of origin of the serotonergic descending pathway) to the spinal cord, comprise one of the main neurotransmitter systems mediating descending modulation of spinal neuronal activity. Animal studies report variably on the function of descending controls from the RVM and of 5-HT in nociceptive transmission (Bannister Ribociclib et al., 2009 and Millan, 2002). Early studies investigating blockade of RVM activity and loss of 5-HT modulation have pointed to a loss of inhibitory control resulting in increased pain behaviours (Millan, 2002). However, in addition to descending inhibition, a wealth of evidence now exists for a descending excitatory drive from the RVM modulating spinal nociceptive transmission, which involves the activation of serotonergic pathways (Bannister et al., 2009, Dogrul et al., 2009 and Wei et al., 2010). The heterogeneous nature of the 5-HT receptor family underlies the bidirectional effect of the neurotransmitter. To date, seven different receptor subfamilies have been identified which vary with respect to their localisation, coupling and ligand
binding properties (Alexander et al., 2008). A number of reports have linked descending facilitation from the brainstem to activation of spinal 5-HT3 receptors (Dogrul et al., 2009, Rygh et al., 2006, Suzuki et al., 2002 and Svensson Cepharanthine et al., 2006). For instance, using in vivo electrophysiological methods, we have demonstrated a pro-nociceptive function for spinal 5-HT3 receptors on spinal neuronal activity since topical spinal application of the selective antagonist ondansetron significantly reduced spinal neuronal activity in normal and pathaphysiological conditions ( Rahman et al., 2004, Suzuki et al., 2002 and Suzuki et al., 2004). This pronociceptive role for spinal 5-HT3 receptors has also been borne out by behavioural and anatomical studies ( Dogrul et al., 2009, Oatway et al., 2004, Svensson et al., 2006 and Zeitz et al.