Chronic paternal morphine exposure increases sensitivity to morphine-derived antinociception

ABSTRACT: Preclinical studies suggest that parental exposure to drugs of abuse such as opioids can have profound and long-lasting effects on reward processing and drug sensitivity across generations. However, little is known about the impact of long-term paternal morphine exposure on sensitivity to morphine-derived antinociception in offspring. We developed a novel sub-second pain scale with statistical modeling and machine learning to measure mechanical nociception in Long Evans and Sprague Dawley male and female rats. Next, we used this rat pain scale with a multigenerational paternal morphine exposure paradigm to determine whether chronic paternal morphine exposure impacts pain sensitivity in offspring. Finally, we used RNA sequencing to identify potential molecular correlates of sire exposure to morphine on offspring. Surprisingly, we found that von Frey hair filaments (VFHs), the most commonly-used noxious mechanical stimuli to test pain sensitivity, are not painful to rats as measured by this novel rat pain scale. Male progeny produced from morphine-treated sires did not exhibit any baseline changes in sensitivity to noxious mechanical stimuli but had greater sensitivity to the antinociceptive properties of morphine. Changes in gene expression within the periaqueductal gray, including primary members of the RGS family of proteins, were identified that may play a role in modified sensitivity to morphine within offspring. These findings reveal nuanced responses to VFHs that should be considered in future pain studies and demonstrate that long-term paternal exposure to morphine increases sensitivity to morphine-derived analgesia in the subsequent male generation.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE174846 | GEO | 2025/05/20

REPOSITORIES: GEO