Visceral hurting—central sensitisation

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  1. F Cervero
  1. Section of Physiology, University of Alcalá Medical Faculty, Academy Campus Alcalá de Henares, E-28871 Madrid, Spain
  1. Professor F Cervero. FERNANDO.CERVERO{at}UAH.ES

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Visceral pain is the virtually mutual form of hurting produced by illness and one of the well-nigh frequent reasons for patients to seek medical attending. Yet much of what nosotros know about the basic mechanisms of pain derives from experimental studies of somatic nociception. This would be justified if the mechanisms of somatic and visceral pain were like so that data obtained past studying one form of pain could be extrapolated to interpret the mechanisms of the other. Nevertheless, the more we know almost the mechanisms of somatic and visceral sensation the more we realise that these two processes, while having many common features, besides have of import differences. We seldom have any sensory experiences from our internal organs other than pain and discomfort and fifty-fifty when other sensations occur, such as bladder or stomach fullness, these tin hands evolve towards pain if the stimulus persists.

The v main characteristics of visceral hurting—that is, those clinical features that make visceral pain unique—are that visceral pain1:

(i)
is not evoked from all viscera,
(ii)
is non linked to visceral injury,
(3)
is referred to other locations,
(iv)
is lengthened and poorly localised, and
(five)
is accompanied by motor and autonomic reflexes.

Backdrop (i) and (two) generated the notion that some viscera lacked an afferent innervation. We now know that these features of visceral pain are due to the functional properties of the peripheral receptors that innervate different visceral organs and to the fact that many viscera are innervated by receptors whose activation does not evoke witting perception and that are not "sensory" receptors in the strict sense. Properties (3), (iv), and (5) relate to the central organisation of visceral nociceptive mechanisms, peculiarly to the lack of a dissever visceral sensory pathway and to the low proportion of visceral afferent fibres compared with those of somatic origin.

However, primal mechanisms are clearly dependent on peripheral afferent drives. We have recently observed2 that induction of artificial ureteric calculosis in rats results in a marked change in the pattern of ureteric motility. This is characterised by a large increase in the amplitude of contractions, such that they increase from a hateful of about 5–10 mm Hg, well below the nociceptive threshold in normal humans and animals of 20–25 mm Hg, to values around this level. In patients with ureteric calculosis, pain and hyperalgesia often terminal for some time afterward elimination of the stone. Peripheral mechanisms may be responsible for this phenomenon equally we also found the same changes in ureteric movement in rats that spontaneously eliminated the artificial stone during the 1–8 day survival catamenia between stone induction and recording.2

Nociceptive afferent discharges in visceral afferents evoke profound central changes. Prolonged noxious stimulation of the viscera evokes increases in the excitability of viscerosomatic neurones in the spinal string. Such changes are very selective and highly organised as they occur just on those viscerosomatic cells that are driven by the conditioning visceral stimulus. In somatic nociceptive systems, a mutual correlate of the enhanced excitability is the frequency dependent increment in neuronal excitability known every bit "wind upward".

The phenomenon of wind up is mostly regarded as a display of central sensitisation. However, visceral nociceptive neurones, which are quite capable of showing increased excitability on prolonged noxious stimulation, practice not "wind up"i as somatic neurones practice, thus demonstrating again the differences between somatic and visceral nociceptive systems and casting doubtfulness on the office of "wind up" as a generator of fundamental sensitisation and hyperalgesia.

The increases in excitability of spinal cord nociceptive neurones induced by repetitive baneful stimulation may be due to the properties of the neuronal network activated by the stimuli or to release of certain transmitters, or both. Excitability increases could exist mediated by positive feedback loops between spinal and supraspinal structures. These loops are particularly prominent on visceral nociceptive neurones and could exist responsible for the enhanced motor and autonomic reflexes that frequently accompany visceral pain states.3 The postsynaptic actions of the neurotransmitters released by noxious stimuli can also contribute to the enhanced excitability of visceral nociceptive pathways following periods of prolonged stimulation.

Glutamate is a major transmitter in the spinal cord, and theN-methyl-d-aspartate (NMDA) glutamate receptor subtype has been proposed as having a item role in mediating persistent pain and hyperalgesia in the spinal cord. In a recent study from our laboratory, we observed a differential outcome of NMDA receptor antagonists on the reflex responses in anaesthetised rats to acute noxious stimuli applied to normal somatic and visceral tissue. While the responses to graded baneful distensions of the ureter were dose dependently inhibited by the NMDA receptor ion channel blocker ketamine, the responses to graded compression stimuli of one hindpaw were not affected.4 Nosotros believe that acute baneful stimulation of normal visceral tissue provokes intense responses that recruit neural mechanisms mediated by NMDA receptors, whereas in somatic pathways these mechanisms are recruited only by an enhanced peripheral input such as that produced after injury or inflammation.

Substance P has long been thought to exist involved with nociceptive processing as it is expressed in pocket-size diameter primary afferents, nigh of which are connected to peripheral nociceptors. However, the published information on the furnishings of neurokinin (NK) 1 receptor antagonists in phase 3 pain in animal models is somewhat contradictory. The recent development of mutant mice strains with disruptions of the gene coding for the NK1 receptor has provided an alternative method to investigate the role of substance P and NK1 receptors in pain.5 Data from experiments using receptor antagonists and from experiments in mutant mice propose that the role of substance P and the NK1 receptor is particularly important in persistent visceral hurting, especially that with a neurogenic component.

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British Guild of Gastroenterology