Background: The effects of Alzheimer's disease (AD) pathology on the experience of pain are poorly understood. Objective: To understand the pathophysiological mechanisms underlying pain sensory transmission in the transgenic mouse model of AD, CRND8. Methods: We explored AD-related pathology in the spinal cord and dorsal root ganglia of 18-week-old female CRND8 mice. We assessed nociceptive responses to both acute heat stimuli and persistent inflammatory pain in CRND8 mice and non-transgenic (non-Tg) littermates. In addition, we searched for differences in biochemical correlates of inflammatory pain between CRND8 and non-Tg mice. Finally, we investigated the excitability of dorsal horn noc iceptive neurons in spinal cord slices from CRND8 and non-Tg mice. Results: We demonstrated the presence of intracellular AD-like pathology in the spinal cord and in the dorsal root ganglia nociceptive sensory neurons of CRND8 mice. We found that CRND8 mice had a reduced susceptibility to acute noxious heat stimuli and an increased sensitivity to tonic inflammatory pain. Tonic inflammatory pain correlated with a lack of induction of pro-opiomelanocortin in the spinal cord of CRND8 mice as compared to non-Tg mice. Electrophysiological recording in acute spinal cord slice preparations indicated an increased probability of glutamate release at the membrane of dorsal horn nociceptive neurons in CRND8 mice. Conclusion: This study suggests that an increased thermal tolerance and a facilitation of nociception by peripheral inflammation can coexist in AD.

Increased Heat Pain Tolerance but Hyperalgesia to Tonic Inflammatory Pain in the CRND8 Mouse Model of Alzheimer's Disease / Merlo, Sara; Costa, Lara; Chiechio, Santina; Busceti, Carla Letizia; Ciranna, Lucia; Santangelo, Rosa; Sortino, Maria Angela; Fornai, Francesco; Nicoletti, Ferdinando; Copani, Agata. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1875-8908. - 96:1(2023), pp. 77-91. [10.3233/JAD-230148]

Increased Heat Pain Tolerance but Hyperalgesia to Tonic Inflammatory Pain in the CRND8 Mouse Model of Alzheimer's Disease

Busceti, Carla Letizia;Nicoletti, Ferdinando;Copani, Agata
2023

Abstract

Background: The effects of Alzheimer's disease (AD) pathology on the experience of pain are poorly understood. Objective: To understand the pathophysiological mechanisms underlying pain sensory transmission in the transgenic mouse model of AD, CRND8. Methods: We explored AD-related pathology in the spinal cord and dorsal root ganglia of 18-week-old female CRND8 mice. We assessed nociceptive responses to both acute heat stimuli and persistent inflammatory pain in CRND8 mice and non-transgenic (non-Tg) littermates. In addition, we searched for differences in biochemical correlates of inflammatory pain between CRND8 and non-Tg mice. Finally, we investigated the excitability of dorsal horn noc iceptive neurons in spinal cord slices from CRND8 and non-Tg mice. Results: We demonstrated the presence of intracellular AD-like pathology in the spinal cord and in the dorsal root ganglia nociceptive sensory neurons of CRND8 mice. We found that CRND8 mice had a reduced susceptibility to acute noxious heat stimuli and an increased sensitivity to tonic inflammatory pain. Tonic inflammatory pain correlated with a lack of induction of pro-opiomelanocortin in the spinal cord of CRND8 mice as compared to non-Tg mice. Electrophysiological recording in acute spinal cord slice preparations indicated an increased probability of glutamate release at the membrane of dorsal horn nociceptive neurons in CRND8 mice. Conclusion: This study suggests that an increased thermal tolerance and a facilitation of nociception by peripheral inflammation can coexist in AD.
2023
Alzheimer’s disease; dementia; dorsal root ganglia; nociceptive neurons; spinal cord; transgenic AD mice
01 Pubblicazione su rivista::01a Articolo in rivista
Increased Heat Pain Tolerance but Hyperalgesia to Tonic Inflammatory Pain in the CRND8 Mouse Model of Alzheimer's Disease / Merlo, Sara; Costa, Lara; Chiechio, Santina; Busceti, Carla Letizia; Ciranna, Lucia; Santangelo, Rosa; Sortino, Maria Angela; Fornai, Francesco; Nicoletti, Ferdinando; Copani, Agata. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1875-8908. - 96:1(2023), pp. 77-91. [10.3233/JAD-230148]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1707221
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 1
social impact