Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse

Tasuku Akiyama, M. Nagamine, A. Davoodi, M. Iodi Carstens, F. Cevikbas, M. Steinhoff, E. Carstens

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 μg/μl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 μg·ml–1·min–1), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1- sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans.

Original languageEnglish (US)
Article numberA042
Pages (from-to)2528-2534
Number of pages7
JournalJournal of Neurophysiology
Volume114
Issue number4
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Fingerprint

Posterior Horn Cells
Bombesin
Endothelin-1
Neurons
Intradermal Injections
Capsaicin
Chloroquine
Pain
Histamine
Gastrin-Releasing Peptide
Animal Behavior
Nociceptors
Pentobarbital
Inbred C57BL Mouse
Heating
Hot Temperature

Keywords

  • Bombesin
  • Endothelin-1
  • Itch
  • Pain
  • Superficial dorsal horn

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Akiyama, T., Nagamine, M., Davoodi, A., Iodi Carstens, M., Cevikbas, F., Steinhoff, M., & Carstens, E. (2015). Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse. Journal of Neurophysiology, 114(4), 2528-2534. [A042]. https://doi.org/10.1152/jn.00723.2015

Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse. / Akiyama, Tasuku; Nagamine, M.; Davoodi, A.; Iodi Carstens, M.; Cevikbas, F.; Steinhoff, M.; Carstens, E.

In: Journal of Neurophysiology, Vol. 114, No. 4, A042, 01.10.2015, p. 2528-2534.

Research output: Contribution to journalArticle

Akiyama, T, Nagamine, M, Davoodi, A, Iodi Carstens, M, Cevikbas, F, Steinhoff, M & Carstens, E 2015, 'Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse', Journal of Neurophysiology, vol. 114, no. 4, A042, pp. 2528-2534. https://doi.org/10.1152/jn.00723.2015
Akiyama, Tasuku ; Nagamine, M. ; Davoodi, A. ; Iodi Carstens, M. ; Cevikbas, F. ; Steinhoff, M. ; Carstens, E. / Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse. In: Journal of Neurophysiology. 2015 ; Vol. 114, No. 4. pp. 2528-2534.
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abstract = "Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 μg/μl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 μg·ml–1·min–1), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48{\%} responded to brush and pinch [wide dynamic range (WDR)] and 52{\%} to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50{\%} to cooling, and >70{\%} to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1- sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans.",
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