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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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The brain activations induced by butorphanol, analyzed in comparison with placebo were found in the midbrain: ventral tegmental area (VTA), periaqueductal gray (PAG), raphé nucleus; in the thalamus, precuneus and cerebellum. x, y, z – MNI standard space coordinates.
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Figure 4: The brain activations induced by butorphanol, analyzed in comparison with placebo were found in the midbrain: ventral tegmental area (VTA), periaqueductal gray (PAG), raphé nucleus; in the thalamus, precuneus and cerebellum. x, y, z – MNI standard space coordinates.

Mentions: Butorphanol induced a significant deactivation of the claustrum, putamen, anterior and posterior insulae (Fig. 3a, in blue; Table 1), which were activated during itch processing by histamine and cowhage. The deactivating effect of butorphanol appeared to overlap to a substantial extent with the areas activated by histamine itch in the contralateral insula and claustrum (in red, Fig. 3b), but did not fully overlap (i.e. counter) the responses evoked by cowhage at the ipsilateral sites (in green, Fig. 3c). Butorphanol induced significant activations in the midbrain, in areas consistent with the location of VTA, raphé nucleus, substantia nigra, red nucleus and periaqueductal gray matter (PAG), as well as cerebellum, precuneus and thalamus, when analyzed in contrast to the placebo (Figure 4, Table 1).


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 brain activations induced by butorphanol, analyzed in comparison with placebo were found in the midbrain: ventral tegmental area (VTA), periaqueductal gray (PAG), raphé nucleus; in the thalamus, precuneus and cerebellum. x, y, z – MNI standard space coordinates.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: The brain activations induced by butorphanol, analyzed in comparison with placebo were found in the midbrain: ventral tegmental area (VTA), periaqueductal gray (PAG), raphé nucleus; in the thalamus, precuneus and cerebellum. x, y, z – MNI standard space coordinates.
Mentions: Butorphanol induced a significant deactivation of the claustrum, putamen, anterior and posterior insulae (Fig. 3a, in blue; Table 1), which were activated during itch processing by histamine and cowhage. The deactivating effect of butorphanol appeared to overlap to a substantial extent with the areas activated by histamine itch in the contralateral insula and claustrum (in red, Fig. 3b), but did not fully overlap (i.e. counter) the responses evoked by cowhage at the ipsilateral sites (in green, Fig. 3c). Butorphanol induced significant activations in the midbrain, in areas consistent with the location of VTA, raphé nucleus, substantia nigra, red nucleus and periaqueductal gray matter (PAG), as well as cerebellum, precuneus and thalamus, when analyzed in contrast to the placebo (Figure 4, Table 1).

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