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Identification and understanding of the various processes which may underlie the pathogenesis of functional bowel diseases are complex. Apart from the possible contributions of misperception or error, there seem to be four major types of processes potentially involved, namely: (a) motor or secretomotor abnormalities; (b) enteric nervous dysfunction; (c) abnormal sensation; and (d) abnormal central responses to sensory input from peripheral sensations, leading to abnormal responses of efferent autonomic, endocrine, or behavioural activities. In this brief review I will focus on (c) and (d).
Unknown at the present time are: (i) the extent to which visceral pain emanates from hypersensitivity to mechanical, chemical, or other stimuli and (ii) the ways in which learning, conditioning, habituation, long term and short term memory, and explicit or implicit memory or neuronal potentiation, participate in these processes, including the possibility that plastic “memory” (for want of a better word) in peripheral cells and their components (dendrites, nuclei, or axons) or connections (synapses, ganglia, neural networks) is involved in ways in which early or repetitive traumatic life events might act to condition patients to have abnormal sensory responses to normal stimuli at a later stage. My particular inquiries have principally explored the answers to two questions: (1) Are prostaglandins (PGs) involved in these processes? (2) Is PG production from arachidonic acid, the action of cyclooxygenase 2 (COX-2), most relevant to functional bowel disease?
Various types of eicosanoids are made by a variety of cells of the nervous system including neurones (benign and neoplastic) in cell culture, nerve cells in brain, spinal cord, autonomic nerves, and peripheral ganglia, and also in juxtaneuronal cells (astroglia and capillary endothelia) in various sites: products include those of both the cyclooxygenase and lipoxygenase pathways.1 While much is known about …
Footnotes
- Abbreviations used in this paper:
- COX
- cyclooxygenase
- NGF
- nerve growth factor
- IEGs
- immediate early genes
- PGs
- prostaglandins
- NMDA
- N-methyl-d-aspartate