Model of Chronic Itch in Aged Mice: Beneficial Effects of Drugs Affecting Descending Modulatory Systems

Acta Derm Venereol. 2024 May 15:104:adv39950. doi: 10.2340/actadv.v104.39950.

Abstract

Pruritus in the elderly, particularly those cases without skin dryness or other identifiable causes, makes treatment challenging due to the lack of evidence regarding the therapeutic effects of antipruritics. This study proposes an age-related alloknesis mouse model for an evaluation system for such cases, and aimed to investigate the effectiveness and mechanisms of action of several drugs commonly used as antipruritics in Japan, utilizing this model. Mice 69-80 weeks old were used as aged mice, and the level of mechanical alloknesis was counted as the number of scratching behaviours in response to innocuous stimuli. Bepotastine, neurotropin, pregabalin, baricitinib, and abrocitinib were used as antipruritics, and yohimbine and methysergide as inhibitors of the descending inhibitory pathway. The findings suggest that mechanical alloknesis in aged mice is a suitable animal model for assessing pruritus in the elderly without xerosis, and pregabalin, neurotropin, baricitinib, and abrocitinib may be effective antipruritics in the elderly through activating both the noradrenergic and serotonergic descending inhibitory pathways. These findings may be useful for the selection of antipruritics for pruritus in the elderly without skin lesions or dryness.

MeSH terms

  • Age Factors
  • Aging / drug effects
  • Animals
  • Antipruritics* / pharmacology
  • Antipruritics* / therapeutic use
  • Azetidines / pharmacology
  • Azetidines / therapeutic use
  • Behavior, Animal / drug effects
  • Chronic Disease
  • Disease Models, Animal*
  • Male
  • Mice
  • Pregabalin / pharmacology
  • Pregabalin / therapeutic use
  • Pruritus* / drug therapy
  • Purines / pharmacology
  • Purines / therapeutic use
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Sulfonamides / pharmacology

Grants and funding

Funding sources This work was supported by JSPS KAKENHI grant numbers 20H03568 (KT), 20K08680 (EK), 23K18407 (EK), 22H02956 (MT), 24K02265 (EK) a grant from Lydia O’Leary Memorial Pias Dermatological Foundation 2022 (EK) and research support from Nippon Zoki Pharmaceutical Company.