Age-related molecular changes in the lumbar dorsal root ganglia of mice: Signs of sensitization, and inflammatory
Kathleen Vincent1,2, Chethana Prabodhanie Gallage Dona1,3, Todd J Albert3,4
1Orthopedic Soft Tissue Research Program Hospital for Special Surgery New York New York USA.
Abstract:
Aging is a major risk factor for numerous painful, inflammatory, and degenerative diseases including disc degeneration. A better understanding of how the somatosensory nervous system adapts to the changing physiology of the aging body will be of great significance for our expanding aging population. Previously, we reported that chronological aging of mouse lumbar discs is pathological and associated with behavioral changes related to pain. It is established that with age and degeneration the lumbar discs become inflammatory and innervated. Here we analyze the aging lumbar dorsal root ganglia (DRGs) and spinal cord dorsal horn (SCDH) in mice between 3 and 24 months of age for age-related somatosensory adaptations. We observe that as mice age there are signs of peripheral sensitization, and response to inflammation at the molecular and cellular level in the DRGs. From 12 months onwards the mRNA expression of vasodilator and neurotransmitter, Calca (CGRP); stress (and survival) marker, Atf3; and neurotrophic factor, Bdnf, increases linearly with age in the DRGs. Further, while the mRNA expression of neuropeptide, Tac1, precursor of Substance P, did not change at the transcriptional level, TAC1 protein expression increased in 24-month-old DRGs. Additionally, elevated expression of NFκB subunits, Nfkb1 and Rela, but not inflammatory mediators, Tnf, Il6, Il1b, or Cox2, in the DRGs suggest peripheral nerves are responding to inflammation, but do not increase the expression of inflammatory mediators at the transcriptional level. These results identify a progressive, age-related shift in the molecular profile of the mouse somatosensory nervous system and implicates nociceptive sensitization and inflammatory response.
