Article

Recent advances in chronic visceral pain.

The Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Whitechapel, London, UK.
Current opinion in supportive and palliative care 07/2008; 2(2):116-21. DOI: 10.1097/SPC.0b013e328300548a
Source: PubMed

ABSTRACT Chronic visceral pain is one of the most common causes of morbidity in the general population. Despite a gargantuan effort from academia and the pharmaceutical industry, an integrated understanding of the pathophysiological mechanisms of chronic visceral pain, particularly with respect to functional gastrointestinal disorders, remains incomplete.
Advances in our understanding of the structure and function of the microanatomy of nociception has led to the identification of a number of ion channels, neurotransmitter receptors and trophic factors that may be intimately involved in chronic visceral pain. These advances have been paralleled with those in the fields of genetics, neurophysiology and functional neuroimaging. These advances have allowed the objective assessment of central processing of visceral sensation and furthermore the factors that may modulate this process in health and disease.
These findings have important implications for the future direction of research. The real challenge for the future progress is to further characterize patients with chronic visceral pain in terms of their clinical phenotype, genotyping and nociceptive physiology on an individual basis towards the development of more efficacious therapeutic strategies.

0 Bookmarks
 · 
102 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Visceral pain is the most common reason for physician visits in US. Glutamate is the major excitatory neurotransmitter and mediates visceral nociceptive neuro-transmission and hypersensitivity. Removal of extracellular glutamate is predominantly mediated by glial glutamate transporter-1 (GLT-1). The pharmacological approach to up-regulate GLT-1 by 1 week administration of ceftriaxone (CTX) has been successful to mitigate visceral nociception. The present study shows that intrathecal delivery of selective GLT-1 antagonist dihydrokainate reversed CTX-blunted visceral nociceptive response, suggesting a spinal site of action. The role of GLT-1 up-regulation in animal models of colitis was studied. CTX treatment reversed TNBS-induced visceral hypersensitivity. In addition, CTX treatment initiated one week after the onset of DSS-induced visceral inflammation also attenuated visceral hypersensitivity, revealing a potential therapeutic effect. Cephalothin, a cephalosporin antibiotic lacking GLT-1 induction activity, failed to attenuate visceral nociception. CTX-induced changes in fecal microbiota do not support a role of probiotic effects in mitigating visceral nociception/hypersensitivity. Finally, adeno-associated virus serotype 9-mediated GLT-1 over-expression was effective to mitigate visceromotor response to 60 mmHg colo-rectal distension. These studies indicate that GLT-1 over-expression is a novel and effective method to attenuate visceral nociception, and is deserving of further study as a translationally relevant approach to treat visceral pain.
    12/2011; 2011:507029. DOI:10.1155/2011/507029
    This article is viewable in ResearchGate's enriched format
  • [Show abstract] [Hide abstract]
    ABSTRACT: Functional chronic visceral pain (FCVP) is one of the most common causes of morbidity in the general population. Pain perceived within the abdomen may occur due to a range of different mechanisms according to the organ and their afferent pathways. Advances in our understanding of the complexities of FCVP could lead to the exploitation of contemporary research in order to develop and utilize our understanding of neurobiological and psychobiological visceral mechanisms in a clinical setting. This progression, together with increasing amounts of epidemiological and gender based information concerning specific abdominal pain syndromes can allow us to develop assessment tools that go beyond disease only analysis and move toward a more comprehensive assessment model so that patients may have access to expert or multidisciplinary management sooner, rather than later. Based on current evidence, one must consider the main contributors to pain, whether it is nociceptive, neuropathic or psychosocial or as is common with FCVP, a combination of all three. AIM: This comprehensive assessment model should encompass not only systematic evaluation for reliable communication, but should also progress toward idiographic diagnosis relating to the uniqueness of the patient. This model should be practical in a multidisciplinary setting, taking into account the multi-faceted nature of this presentation.
    Pain Medicine 12/2010; 12(4):552-64. DOI:10.1111/j.1526-4637.2010.01025.x · 2.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Summary Functional abdominal pain syndrome is characterised by frequent or continuous abdominal pain associated with a degree of loss of daily activity. It has a reported population prevalence of between 0.5% and 1.7%, with a female preponderance. The pathophysiology of functional abdominal pain is incompletely understood although it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory systems may have an important role. The management of patients with functional abdominal pain requires a tailored multidisciplinary approach in a supportive and empathetic environment in order to develop an effective therapeutic relationship. Patient education directed towards an explanation of the pathophysiology of functional abdominal pain is in our opinion a prerequisite step and provides the rationale for the introduction of interventions. Interventions can usefully be categorised into general measures, pharmacotherapy, psychological interventions and 'step-up' treatments. Pharmacotherapeutic/step-up options include tricyclic antidepressants, serotonin noradrenergic reuptake inhibitors and the gabapentinoids. Psychological treatments include cognitive behavioural therapy and hypnotherapy. However, the objective evidence base for these interventions is largely derived from other chronic pain syndrome, and further research is warranted in adult patients with functional abdominal pain.
    Journal of the Royal Society of Medicine 09/2014; 107(9):347-354. DOI:10.1177/0141076814540880 · 2.02 Impact Factor