Limits...
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.

Show MeSH

Related in: MedlinePlus

a) The effect of intranasal butorphanol (1 mg) on cerebral activity was analyzed in comparison to a placebo (0.9% intranasal saline). Butorphanol extensively deactivated bilaterally an area situated between the insular cortex and putamen, which coincides with the anatomical location of the claustrum, while also deactivating the left insular cortex and the putamen. b) The activations induced by histamine itch (red) are overlaid with the deactivations induced by butorphanol (blue; vs. placebo), displaying a significant conjunction in the contralateral insula, claustrum and putamen. c) Overlay of brain responses induced by histamine itch (red), cowhage itch (green) and the deactivations induced by butorphanol (blue). x, y, z - Montreal Neurological Institute (MNI) standard space coordinates. Z score > 2.3, p<0.05.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4289457&req=5

Figure 3: a) The effect of intranasal butorphanol (1 mg) on cerebral activity was analyzed in comparison to a placebo (0.9% intranasal saline). Butorphanol extensively deactivated bilaterally an area situated between the insular cortex and putamen, which coincides with the anatomical location of the claustrum, while also deactivating the left insular cortex and the putamen. b) The activations induced by histamine itch (red) are overlaid with the deactivations induced by butorphanol (blue; vs. placebo), displaying a significant conjunction in the contralateral insula, claustrum and putamen. c) Overlay of brain responses induced by histamine itch (red), cowhage itch (green) and the deactivations induced by butorphanol (blue). x, y, z - Montreal Neurological Institute (MNI) standard space coordinates. Z score > 2.3, p<0.05.

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)

a) The effect of intranasal butorphanol (1 mg) on cerebral activity was analyzed in comparison to a placebo (0.9% intranasal saline). Butorphanol extensively deactivated bilaterally an area situated between the insular cortex and putamen, which coincides with the anatomical location of the claustrum, while also deactivating the left insular cortex and the putamen. b) The activations induced by histamine itch (red) are overlaid with the deactivations induced by butorphanol (blue; vs. placebo), displaying a significant conjunction in the contralateral insula, claustrum and putamen. c) Overlay of brain responses induced by histamine itch (red), cowhage itch (green) and the deactivations induced by butorphanol (blue). x, y, z - Montreal Neurological Institute (MNI) standard space coordinates. Z score > 2.3, p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: a) The effect of intranasal butorphanol (1 mg) on cerebral activity was analyzed in comparison to a placebo (0.9% intranasal saline). Butorphanol extensively deactivated bilaterally an area situated between the insular cortex and putamen, which coincides with the anatomical location of the claustrum, while also deactivating the left insular cortex and the putamen. b) The activations induced by histamine itch (red) are overlaid with the deactivations induced by butorphanol (blue; vs. placebo), displaying a significant conjunction in the contralateral insula, claustrum and putamen. c) Overlay of brain responses induced by histamine itch (red), cowhage itch (green) and the deactivations induced by butorphanol (blue). x, y, z - Montreal Neurological Institute (MNI) standard space coordinates. Z score > 2.3, p<0.05.
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