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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

The cerebral mechanism underlying butorphanol’s suppression of histamine itch was analyzed by a General Linear Model paired t test (contrast) of perfusion weighted images between the following states: [(histamine + drug) vs. drug] vs. [(histamine + placebo) vs. placebo]. This analysis showed that the inhibition of histamine itch by butorphanol was paralleled by the activation of nucleus accumbens and septal nuclei. x, y, z – MNI standard space coordinates.
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Figure 5: The cerebral mechanism underlying butorphanol’s suppression of histamine itch was analyzed by a General Linear Model paired t test (contrast) of perfusion weighted images between the following states: [(histamine + drug) vs. drug] vs. [(histamine + placebo) vs. placebo]. This analysis showed that the inhibition of histamine itch by butorphanol was paralleled by the activation of nucleus accumbens and septal nuclei. x, y, z – MNI standard space coordinates.

Mentions: To identify the key brain areas involved in the mediation of the antipruritic effect of butorphanol, we have implemented a study design that allowed us to construct a stepwise contrast between active and control states, when itch was induced in the presence of the drug vs. placebo (Methods). This global analysis (performed for the whole-brain) revealed that nucleus accumbens (NAc), septal nuclei and the adjacent septal area of the anterior cingulate cortex were significantly activated during the inhibition of histamine itch (Figure 5, Table 1). These results suggest that suppression of histamine itch was significantly mediated by the activation of these formations. These results were not found in identical contrasts run for the effect of butorphanol on cowhage itch or heat pain (which did not yield significant results).


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)

The cerebral mechanism underlying butorphanol’s suppression of histamine itch was analyzed by a General Linear Model paired t test (contrast) of perfusion weighted images between the following states: [(histamine + drug) vs. drug] vs. [(histamine + placebo) vs. placebo]. This analysis showed that the inhibition of histamine itch by butorphanol was paralleled by the activation of nucleus accumbens and septal nuclei. x, y, z – MNI standard space coordinates.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: The cerebral mechanism underlying butorphanol’s suppression of histamine itch was analyzed by a General Linear Model paired t test (contrast) of perfusion weighted images between the following states: [(histamine + drug) vs. drug] vs. [(histamine + placebo) vs. placebo]. This analysis showed that the inhibition of histamine itch by butorphanol was paralleled by the activation of nucleus accumbens and septal nuclei. x, y, z – MNI standard space coordinates.
Mentions: To identify the key brain areas involved in the mediation of the antipruritic effect of butorphanol, we have implemented a study design that allowed us to construct a stepwise contrast between active and control states, when itch was induced in the presence of the drug vs. placebo (Methods). This global analysis (performed for the whole-brain) revealed that nucleus accumbens (NAc), septal nuclei and the adjacent septal area of the anterior cingulate cortex were significantly activated during the inhibition of histamine itch (Figure 5, Table 1). These results suggest that suppression of histamine itch was significantly mediated by the activation of these formations. These results were not found in identical contrasts run for the effect of butorphanol on cowhage itch or heat pain (which did not yield significant results).

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