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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

Timeline of experimental interventions and functional MRI sessions. Subjects were assigned to go into either the placebo or the butorphanol arm first, following a randomization scheme, and then they switched to the other arm. The two parts of the experiment were performed 7 days apart. The post-treatment perfusion scan was started 40 minutes after drug (or placebo) administration. The stimulation sequence using the three sensory modalities was randomized for each experiment. Perfusion scans following itch or pain interventions were started approximately 45 minutes post-drug (or placebo) administration, at the peak of the pharmacological action of intranasal butorphanol. Each perfusion ASL scan lasted 4 min 54 s.
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Figure 1: Timeline of experimental interventions and functional MRI sessions. Subjects were assigned to go into either the placebo or the butorphanol arm first, following a randomization scheme, and then they switched to the other arm. The two parts of the experiment were performed 7 days apart. The post-treatment perfusion scan was started 40 minutes after drug (or placebo) administration. The stimulation sequence using the three sensory modalities was randomized for each experiment. Perfusion scans following itch or pain interventions were started approximately 45 minutes post-drug (or placebo) administration, at the peak of the pharmacological action of intranasal butorphanol. Each perfusion ASL scan lasted 4 min 54 s.

Mentions: Functional MRI cerebral perfusion images were acquired by Arterial Spin Labeling, using a 3-D Grase-Propeller protocol (Tan et al, 2011). Perfusion images were acquired at rest prior to drug (or placebo) administration, and 40 minutes after drug/placebo to capture the effect on cerebral perfusion prior to itch/pain stimulation. Images were subsequently acquired immediately after itch/pain induction, after an interval of 45 minutes post-treatment (Fig. 1). This was carefully chosen to coincide exactly with the moment when the pharmacodynamic effect of butorphanol was at its peak (Davis et al, 2004).


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)

Timeline of experimental interventions and functional MRI sessions. Subjects were assigned to go into either the placebo or the butorphanol arm first, following a randomization scheme, and then they switched to the other arm. The two parts of the experiment were performed 7 days apart. The post-treatment perfusion scan was started 40 minutes after drug (or placebo) administration. The stimulation sequence using the three sensory modalities was randomized for each experiment. Perfusion scans following itch or pain interventions were started approximately 45 minutes post-drug (or placebo) administration, at the peak of the pharmacological action of intranasal butorphanol. Each perfusion ASL scan lasted 4 min 54 s.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Timeline of experimental interventions and functional MRI sessions. Subjects were assigned to go into either the placebo or the butorphanol arm first, following a randomization scheme, and then they switched to the other arm. The two parts of the experiment were performed 7 days apart. The post-treatment perfusion scan was started 40 minutes after drug (or placebo) administration. The stimulation sequence using the three sensory modalities was randomized for each experiment. Perfusion scans following itch or pain interventions were started approximately 45 minutes post-drug (or placebo) administration, at the peak of the pharmacological action of intranasal butorphanol. Each perfusion ASL scan lasted 4 min 54 s.
Mentions: Functional MRI cerebral perfusion images were acquired by Arterial Spin Labeling, using a 3-D Grase-Propeller protocol (Tan et al, 2011). Perfusion images were acquired at rest prior to drug (or placebo) administration, and 40 minutes after drug/placebo to capture the effect on cerebral perfusion prior to itch/pain stimulation. Images were subsequently acquired immediately after itch/pain induction, after an interval of 45 minutes post-treatment (Fig. 1). This was carefully chosen to coincide exactly with the moment when the pharmacodynamic effect of butorphanol was at its peak (Davis et al, 2004).

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