Importance of anti- and pro-nociceptive mechanisms in human disease

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Abstract
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 gastro-oesophageal 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).