Visceral pain-peripheral sensitisation.

The viscera receive dual sensory innervation. The majority of visceral sensory fibres terminate in the spinal cord but sensory fibres contained in the vagus and pelvic nerves, which terminate in the brain stem and lumbosacral spinal cord, respectively, also innervate the same visceral organs. Figure 1 illustrates this unique pattern of innervation for the gastrointestinal tract, classically referred to as sympathetic and parasympathetic, but more appropriately designated by nerve name (for example, hypogastric nerve, pelvic nerve). Visceral sensory axons are almost exclusively thinly myelinated Aä fibres and unmyelinated C fibres. Activity in most visceral sensory neurones, whether in vagal aVerent fibres or spinal aVerent fibres, does not reach consciousness. For example, there is regular input into the central nervous system from gastric and hepatic chemoreceptors, aortic baroreceptors, etc., that is not perceived. Sensory innervation of the gastrointestinal tract involves all layers of a viscus (mucosa, muscle, and serosa) and visceral receptors exhibit chemosensitivity, thermosensitivity, and mechanosensitivity. Visceral receptors, in fact, are generally polymodal in character (that is, respond to multiple modalities of stimulation). The cell bodies of visceral aVerent neurones, in common with the cell bodies of somatic aVerent neurones, are located in dorsal root ganglia (except for the nodose ganglia which contain the cell bodies of vagal sensory neurones). However, the route visceral aVerent neurones take to the spinal cord typically involves passage through or near prevertebral ganglia (where they can give oV collateral axons to influence autonomic ganglion cell bodies and, accordingly, secretory and motor functions) and paravertebral ganglia (see fig 1). In contrast with aVerent fibres arising from somatic structures, the number of spinal visceral aVerent fibres is estimated to be less than 10% of the total spinal aVerent input from all sources. Some compensation for this relative paucity of visceral input is provided by the significantly greater rostrocaudal intraspinal spread of visceral aVerent fibre terminals. Visceral C fibres have been found to have many more terminal swellings (suggestive of synapses) and terminal areas, and to exhibit rostrocaudal distribution over several spinal cord segments. Experimentally, balloon distension is the most reliable stimulus for hollow visceral organs and is the most widely used stimulus in both human and non-human animal experiments. Accordingly, we know most about the response properties of mechanosensitive visceral aVerent fibres, usually those innervating the muscle layer. Hollow viscera are innervated by two populations of mechanosensitive aVerent fibres: a larger group (70–80%) of fibres have low thresholds for response and a smaller group (20–30%) of aVerent fibres have high thresholds for response (for example, >30 mm Hg distending pressure) (fig 2). Visceral mechanoreceptors that have low thresholds for response (for example, <5 mm Hg) respond within the physiological range. Interestingly, as illustrated in fig 2, these aVerent fibres also respond to distending pressures in the noxious range (>30 mm Hg) and encode stimulus intensity fairly well. Note also that response magnitude in the noxious range is