title: Butorphanol suppression of histamine itch is mediated by nucleus accumbens and septal nuclei: a pharmacological fMRI study.
abstract: Opioid receptors in the central nervous system are important modulators of itch transmission. In this study, we examined the effect of mixed-action opioid butorphanol on histamine itch, cowhage itch, and heat pain in healthy volunteers. Using functional MRI, we investigated significant changes in cerebral perfusion to identify the critical brain centers mediating the antipruritic effect of butorphanol. Butorphanol suppressed the itch induced experimentally with histamine, reduced the intensity of cowhage itch by approximately 35%, and did not affect heat pain sensitivity. In comparison with the placebo, butorphanol produced a bilateral deactivation of claustrum, insula, and putamen, areas activated during itch processing. Analysis of cerebral perfusion patterns of brain processing of itch versus itch inhibition under the effect of the drug revealed that the reduction in cowhage itch by butorphanol was correlated with changes in cerebral perfusion in the midbrain, thalamus, S1, insula, and cerebellum. The suppression of histamine itch by butorphanol was paralleled by the activation of nucleus accumbens and septal nuclei, structures expressing high levels of kappa opioid receptors. In conclusion, important relays of the mesolimbic circuit were involved in the inhibition of itch by butorphanol and could represent potential targets for the development of antipruritic therapy.
authors.affiliation: Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. Electronic address: alexandru.papoiu@gmail.com.
authors.forename: Alexandru D P
authors.initials: ADP
authors.lastname: Papoiu
authors.affiliation: Department of Biomedical Engineering, Virginia Polytechnic Institute & Wake Forest University, Winston-Salem, North Carolina, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kraft
authors.affiliation: Department of Neurobiology & Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Coghill
authors.affiliation: Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Department of Neurobiology & Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Department of Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Department of Dermatology and Itch Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Yosipovitch
mesh_terms: D000328:Adult; D002077:Butorphanol / Q000494:pharmacology*; D018592:Cross-Over Studies; D005260:Female; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D058748:Pain Perception; D011537:Pruritus / Q000517:prevention & control*; D012686:Septal Nuclei / Q000187:drug effects* / Q000502:physiology
chemical_list: D002077:Butorphanol