Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale
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Comparative Study
Serotonin receptors 5-HT1A and 5-HT3 reduce hyperexcitability of dorsal horn neurons after chronic spinal cord hemisection injury in rat.
Spinal cord injury (SCI) results in abnormal pain syndromes in humans. In a rodent model of SCI, T13 spinal hemisection results in allodynia and hyperalgesia due in part to interruption of descending pathways, including serotonergic (5-HT) systems, that leads to hyperexcitability of dorsal horn neurons. To characterize further the role of 5-HT and 5-HT receptor subtypes 5-HT(1A) and 5-HT(3) in neuronal activation after hemisection, we have examined the responsiveness of dorsal horn neurons to a variety of innocuous and noxious peripheral stimuli. ⋯ In hemisected animals, both 5-HT(1A) and 5-HT(3) receptor antagonism reduced the effectiveness of 5-HT, restoring elevated evoked activity by up to 70% at the doses tested. Administration of 5-HT(1A) and 5-HT(3) receptor agonists also decreased hyperexcitability, effects prevented by pretreatment with corresponding antagonists. These results demonstrate the development of denervation supersensitivity to 5-HT following SCI, corroborate behavioral studies showing the effectiveness of 5-HT in reducing allodynia and hyperalgesia after SCI, and contribute to a mechanistic understanding of the role of 5-HT receptor subtypes in chronic central pain.