ABSENCE OF HISTAMINE-INDUCED ITCH IN THE AFRICAN NAKED MOLE-RAT AND "RESCUE" BY SUBSTANCE P

Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P

Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P

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Abstract Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior.We examined histamine-induced itch in the African naked mole-rat (Heterocephalus glaber) and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains.Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG) neurons and identified a population of small diameter neurons activated by histamine, the 6-0 igora vibrance majority of which are also capsaicin-sensitive.

This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents.We have previously shown that naked mole-rats naturally lack substance P (SP) in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord.This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species.

After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection.Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch.In addition, we 15-eg1053cl demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat.

These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.

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