Activation of unmyelinated afferent fibres by mechanical stimuli and inflammation of the urinary bladder in the cat.

Abstract

1. We examined the functional properties of unmyelinated primary afferent neurones innervating the pelvic viscera in twenty-five anaesthetized cats. The axons were isolated from the intact dorsal root and the intact or chronically de-efferented ventral root of the segment S2. All units were electrically identified with electrical stimulation of the pelvic nerve. 2. The responses of the neurones were studied with natural stimulation of the urinary bladder using innocuous and noxious increases of intravesical pressure and at the onset of an acute artificial inflammation induced by intraluminal injection of mustard or turpentine oil. 3. Out of 297 unmyelinated afferent units isolated from the dorsal root, seven were excited by an increase of the intravesical pressure during contractions and distension of the urinary bladder. These units were silent when the bladder was empty and had thresholds of 30-50 mmHg which are presumed to be noxious. Further increases of the intravesical pressure were accurately encoded by the discharge rate of the fibres. Out of sixty-eight unmyelinated afferent units isolated from the ventral root none was activated by these stimuli. 4. Intraluminal injection of mustard oil excited mechanosensitive units at short latency. The discharge was not closely related to changes of the intravesical pressure and the units displayed on-going activity after the irritant had been removed. This observation suggests that the units had also chemosensitive properties and that the receptive endings were located in the bladder wall. 5. In sixteen cats ninety-five afferent fibres that were not activated by noxious mechanical stimuli of the urinary bladder were systematically tested with intraluminal injections of mustard oil. This excited 7/67 dorsal root units and 4/28 ventral root units with short latency. Intraluminal application of turpentine oil, tested on twenty-six afferents in four animals, did not produce a rapid excitation. 6. Following the induction of an inflammation some previously non-mechanosensitive units started to respond to changes of intravesical pressure in the biologically relevant pressure range of the urinary bladder. 7. In conclusion, a small subpopulation (2.4%) of unmyelinated visceral afferents responds to high, presumably noxious, intravesical pressure and intraluminal application of chemical irritants. Acute inflammation excites a larger proportion of afferents (9.5%) that are not activated by acute noxious mechanical stimulation of the normal urinary bladder. In the inflamed bladder some previously non-mechanosensitive units started to respond to increases of intravesical pressure. These novel types of chemosensitive receptors may contribute considerably to the pathogenesis of visceral pain states.

Inflammation-Induced Enhancement of the Visceromotor Reflex to Urinary Bladder Distention: Modulation by Endogenous Opioids and the Effects of Early-in-Life Experience With Bladder Inflammation

“…7,14,17 The effects observed in the present studies suggest that two opposing processes contribute to bladder hypersensitivity resulting from acute bladder inflammation. One process is enhanced input, perhaps mediated by inflammation-induced sensitization of primary nociceptive afferents 12,13,19 and/or central sensitization of second-order spinal dorsal horn neurons. 4,40 A second process involves inflammation-induced activation of a reactive opioid system that opposes enhanced input from the bladder.…”

Inflammation-Induced Plasticity of the Afferent Innervation of the Airways

“…arthritis in rats, where afferent neurons that normally fail to respond even to noxious rotation of a rat joint respond to simple flexion following arthritis (18,19). Likewise, afferent fibers insensitive to mechanical distension of the bladder respond to modest distension following inflammation (20). Allergic rhinitis is associated with increased nasal neural responsiveness to stimuli that evoke sneezing, the nasonasal secretory reflex, and axon reflex-mediated plasma extravasation ( Figure 2) (21).…”

Neural Control of the Lower Urinary Tract

“…de Groat et alIn contrast to the low threshold mechano-sensitive Aδ-bladder afferents, the C-bladder afferents in cats are generally mechano-insensitive ("silent C-fibers") (251). Many of these afferents are nociceptive and respond to cold stimuli or chemical/noxious stimuli such as high potassium, low pH, high osmolality, and irritants such as capsaicin and turpentine oil (209,251,394,424).…”

“…Many of these afferents are nociceptive and respond to cold stimuli or chemical/noxious stimuli such as high potassium, low pH, high osmolality, and irritants such as capsaicin and turpentine oil (209,251,394,424). Following exposure to these substances silent afferents become mechanoreceptive and the sensitivity of bladder mechanoreceptors to distension also increases.…”