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Butorphanol suppression of histamine itch is mediated by nucleus accumbens and septal nuclei: a pharmacological fMRI study.

Papoiu AD, Kraft RA, Coghill RC, Yosipovitch G - J. Invest. Dermatol. (2014)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

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.

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Related in: MedlinePlus

Psychophysical data. Butorphanol completely suppressed itch induced with histamine (p<0.001)***, and reduced the intensity of cowhage itch by approximately 35% (p<0.001)***.
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Figure 2: Psychophysical data. Butorphanol completely suppressed itch induced with histamine (p<0.001)***, and reduced the intensity of cowhage itch by approximately 35% (p<0.001)***.

Mentions: Butorphanol completely suppressed the itch induced experimentally with histamine (p<0.001), while it only reduced the intensity of cowhage itch by approximately 35% (p<0.001; paired t tests, two-tails, Bonferroni corrected for multiple comparisons; see Figure 2). Butorphanol did not alter sensitivity to heat pain, or the heat-pain associated unpleasantness. Therefore, at a 1 mg dose it appeared that the mixed-action opioid exerted a differential effect on these 3 sensory modalities.


Butorphanol suppression of histamine itch is mediated by nucleus accumbens and septal nuclei: a pharmacological fMRI study.

Papoiu AD, Kraft RA, Coghill RC, Yosipovitch G - J. Invest. Dermatol. (2014)

Psychophysical data. Butorphanol completely suppressed itch induced with histamine (p<0.001)***, and reduced the intensity of cowhage itch by approximately 35% (p<0.001)***.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4289457&req=5

Figure 2: Psychophysical data. Butorphanol completely suppressed itch induced with histamine (p<0.001)***, and reduced the intensity of cowhage itch by approximately 35% (p<0.001)***.
Mentions: Butorphanol completely suppressed the itch induced experimentally with histamine (p<0.001), while it only reduced the intensity of cowhage itch by approximately 35% (p<0.001; paired t tests, two-tails, Bonferroni corrected for multiple comparisons; see Figure 2). Butorphanol did not alter sensitivity to heat pain, or the heat-pain associated unpleasantness. Therefore, at a 1 mg dose it appeared that the mixed-action opioid exerted a differential effect on these 3 sensory modalities.

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

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.

Show MeSH
Related in: MedlinePlus