Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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Are Descending Control Pathways of the Lower Urinary Tract and Pain Overlapping Systems?

Author(s): Tiziana Mennini, Rodolfo Testa.

Abstract:

The functions of the lower urinary tract (LUT) are dependent upon neural circuits located in the brain, spinal cord and peripheral ganglia, organized as on – off switching circuits to regulate storage and periodic elimination of urine. Damage or disease in any of the nervous pathways controlling the lower urinary tract can cause impairment of normal bladder function. Nociceptive information from different organs are delivered to the dorsal horn of the spinal cord where a network of descending pathways projecting from cerebral structures either suppress or potentiate the passage of the nociceptive messages to the brain. Some of the central structures involved in the micturition reflexes and pain modulation are common, e.g. nucleus raphe magnum, nucleus locus coeruleus alpha, periacqueductal grey, etc. Functionally, however, their effects may be similar or contrasting. The central micturition reflexes and descending control pathways of pain also utilize common transmitters and transmitter systems with similar or different effects on micturition and pain, suggesting a certain degree of overlapping between these systems. All these findings have provided a rich palette of novel mechanisms potentially available for the improved control of LUT and pain. The proliferation of potential analgesic drug targets for the therapeutic manipulation of descending control of pain is testimony of a more (in comparison with LUT) intensive research programme in this field. Nevertheless, with the exception of parenteral administration of μ-opioids and spinal application of α2-AR agonists, no other approach has been extensively validated in the clinic. Great effort should be invested in the characterization of central mechanisms controlling the micturition reflexes, although the possibility to find novel drugs for micturition disorders with central effect appears to be problematic.

Keywords: Micturition reflex, pain, descending pathways, inhibition, facilitation, lower urinary tract

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Article Details

VOLUME: 10
ISSUE: 2
Year: 2010
Page: [113 - 147]
Pages: 35
DOI: 10.2174/187152410791196387
Price: $58