Activation of brain stem nuclei by improgan, a non-opioid analgesic

Brain Research
Julia W NalwalkL B Hough

Abstract

Improgan is a compound developed from histamine antagonists which shows the pre-clinical profile of a highly effective, non-opioid analgesic when administered into the rodent CNS. Pharmacological studies suggest that improgan activates descending pain-relieving circuits, but the brain and spinal sites of action of this drug have not been previously studied. Presently, the effects of intracerebral and intrathecal microinjections of improgan were evaluated on thermal nociceptive responses in rats. Improgan produced large, dose- and time-related reductions in nociceptive responses following administration into the ventrolateral periaqueductal gray (PAG), the dorsal PAG, and the rostral ventromedial medulla (RVM). The drug had no measurable effects after injections into the caudate nucleus, basolateral amygdala, hippocampus, ventromedial hypothalamus, superior colliculi, ventrolateral medulla, or the spinal subarachnoid space. Inactivation of the RVM by muscimol microinjections completely attenuated antincociceptive responses produced by intraventricular improgan. These findings, taken with earlier results, show that, like opioids and cannabinoids, improgan acts in the PAG and RVM to activate descending analgesic systems. Unlike th...Continue Reading

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Citations

Mar 3, 2005·Pharmacology, Biochemistry, and Behavior·J W NalwalkL B Hough
Mar 12, 2013·Acta Pharmacologica Sinica·Xiao-jie ZhangWei-dong Le
Sep 8, 2012·Journal of Neurophysiology·Ryan S PhillipsMary M Heinricher
Mar 6, 2007·Neuropharmacology·Lindsay B HoughRebecca Stadel
Jan 17, 2009·Brain Research Reviews·M M HeinricherB M Lumb
Oct 22, 2011·Brain Research·Phillip J AlbrechtLindsay B Hough
Oct 12, 2005·European Journal of Pharmacology·Lindsay B HoughM José Montero
Jul 10, 2013·European Journal of Pharmacology·Paul HoerbeltLindsay B Hough
Jun 24, 2010·Neuroscience·M M HeinricherL B Hough
Jul 24, 2007·The Journal of Pain : Official Journal of the American Pain Society·Neal C GehaniLindsay B Hough
Jul 16, 2008·Physiological Reviews·Helmut L HaasOliver Selbach

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