The burden of chronic pain to society is enormous. This is both in terms of physical and emotional impact to individuals and carers, in addition to the large financial burden. Current estimates suggest that 11.5–55.2% of individuals worldwide are defined as suffering from chronic widespread pain. 1 A major characteristic of functional disorders such as irritable bowel syndrome (IBS) and inflammatory/neuropathic disorders such as gastrooesophageal reflux and chronic pancreatitis is abdominal discomfort or pain. There is an increasing awareness that many similarities exist mechanistically between somatic chronic pain conditions and the pain witnessed as chronic in IBS and chronic pancreatitis patients. With this realisation there has been a change of focus for researchers of both somatic and visceral pain conditions from peripheral structures as the preferred target of research to the central nervous system (CNS). It has long been recognised that the CNS has a major modulating nociceptive influence that alters resultant pain perception. 2–4 Recent developments in neuroimaging have enabled CNS investigations of visceral pain processing in patients and controls and such studies have highlighted the additional relevance of cognitive and emotional factors in modulating pain perception from physical changes such as plasticity and sensitisation. 5–7 Imaging studies have provided valuable objective information on what is inherently a subjective phenomenon, that for too long has relied upon patients giving a self report of their pain using coarse pain rating scales. 8 Currently, there is a wider imaging literature on pain processing from somatic structures compared with visceral organs. This is probably because it is experimentally (and ethically) easier to perform somatic acute pain paradigms in healthy controls (for instance, using noxious thermal events) compared with more challenging oesophageal or rectal balloon distensions. However, this situation is rapidly changing and in terms of investigating relevant patient groups with pain conditions, there is a rapidly growing literature investigating visceral pain syndromes that competes with imaging studies investigating neuropathic or inflammatory pain (the interested reader is referred to these excellent reviews on imaging pain in the literature9–11). Since 1906 we have known that the brain can modulate in a ‘‘top-down’’manner spinal cord excitability via a tonically active influence that is largely inhibitory in function. Evidence to support this came from work by Sherrington who showed that nociceptive reflexes were enhanced after the spinal cord was transected. 12 Reynolds in 1969 again emphasised the relevance of this phenomenon by showing that focal electrical stimulation in the rat midbrain periaqueductal gray (PAG) produced analgesia strong enough to permit surgery. 13 Over the years, further work showed that stimulation of several brain sites, including the sensory cortex, thalamus, hypothalamus, midbrain, pons, and medulla, produced inhibitory effects on spinal nociceptive processing, suggesting an integrated network of brain regions that produce anti-nociceptive influences in situations where it is desirable to not be behaviourally diverted due to the noxious input. Such situations could include those where there is high arousal as in sports or battle or during placebo analgesia. Many electrophysiological, anatomical, and pharmacological studies determined that these descending influences on spinal nociceptive processing relied on relays in the rostroventral medulla (RVM), including the medial nucleus raphe magnus and it is now accepted that the RVM is the final common output for descending …