Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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Peripheral and Central Mechanisms of Mechanical Allodynia: Neurokinin Receptor for Therapeutic Target

Author(s): Mamoru Takeda, Shigeji Matsumoto.

Abstract:

It is well known that many patients complain about sensory abnormalities involving chronic pain. Mechanical allodynia is defined as pain caused by stimuli that do not normally evoke pain and that which is mediated by lowthreshold mechanoreceptive Aβ-fibers. Understanding of the peripheral and central mechanisms of the mechanical allodynia has been perceived as follows: 1) increased excitability of peripheral and central terminals and their cell bodies, including local paracrine mechanisms; 2) The reduction in inhibition (disinhibition) in the spinal cord (i.e. the decreased inhibitory activity of GABA/glycinergic interneurons; 3) The reorganization of synaptic connections in the spinal dorsal horn (Aβ-afferents sprout into the superficial layer). A suspected possible interaction between noxious and non-noxious sensory signal transmission pathways may play to a key role in the induction of mechanical allodynia. Conversely, substance P is one member of the tachykinin families as well as an important neurotransmitter in nociceptive (Aδ-/C-) primary afferent neurons. Its effect is known to bind primarily to the neurokinin 1 receptor. More recent studies have suggested that mechanical allodynia and their related neuronal responses can be attenuated by pretreatment with a specific neurokinin 1 receptor blocker. Therefore, in this review, we introduce our recent data and discuss the possible interaction between mechanical allodynia and the neurokinin 1 receptor as it pertains to use in therapeutic applications.

Keywords: Pain, mechanical allodynia, substance P, neurokin receptor, sensitization, disinhibition, paracrine/autocrine, Aβ- fibers

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Article Details

VOLUME: 6
ISSUE: 4
Year: 2006
Page: [311 - 320]
Pages: 10
DOI: 10.2174/187152406779010886
Price: $58