Tachykinins as modulators of the micturition reflex in the central and peripheral nervous system.
In the normal urinary bladder, tachykinins (TKs) are expressed in a population of bladder nociceptors that is sensitive to the excitatory and desensitizing effects of capsaicin (i.e., capsaicin-sensitive primary afferent neurons (CSPANs)). Several endobiotics or xenobiotics excite CSPANs and release TKs and other mediators at both the peripheral and spinal cord level. The peripheral release of TKs determines a set of responses (known as neurogenic inflammation) that includes vasodilatation, plasma protein extravasation, smooth muscle contraction and stimulation of afferent nerves. Following chronic inflammation, both immune cells and capsaicin-resistant sensory neurons can de novo express TKs: whether these pools of TKs are releasable and contribute to inflammatory processes is presently unsettled. At the spinal cord level, the release of TKs contributes in determining an altered pattern of vesicourethral reflexes in response to nociceptive stimulation of the bladder by conveying: (a) the afferent transmission to supraspinal sites, and (b) descending or sensory inputs to the sacral parasympathetic nucleus (SPN). Recent evidence also attribute a synergetic role of TKs in the supraspinal modulation of the sensory arm of the micturition reflex. The overall available information suggests that TK receptor antagonists may affect bladder motility/reflexes which occur during different pathological states, while having little influence on the normal motor bladder function.
Lecci
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Pharmacology Department, Menarini Ricerche, via Rismondo 12/A, 50131, Florence, Italy. alecci@menarini-ricerche.it
Maggi
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CA
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002490:Central Nervous System / Q000502:physiology; D006801:Humans; D008959:Models, Neurological; D009619:Nociceptors / Q000502:physiology; D017933:Peripheral Nervous System / Q000502:physiology; D051381:Rats; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D012018:Reflex / Q000502:physiology; D015320:Tachykinins / Q000502:physiology*; D014521:Urethra / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D014554:Urination / Q000502:physiology*
D018039:Receptors, Tachykinin; D015320:Tachykinins; D002211:Capsaicin