Sex-Related Pain Behavioral Differences following Unilateral NGF Injections in a Rat Model of Low Back Pain.

Abstract

Simple SummaryLow back pain (LBP) is a worldwide problem that requires additional studies to better identify its underlying causes. One obstacle encountered is that female-experienced LBP is likely biologically different from male-experienced LBP. Studying the potential sex-differences in animal models may provide a better understanding of the causes of LBP and help to identify new treatments for LBP. We used an animal model to investigate the differences in male and female rats when back muscles on one side were injected with a painful substance called nerve growth factor (NGF). These injections led to sex differences in the behavioral responses to painful stimuli (hyperalgesia) and non-painful stimuli (mechanical hypersensitivity). Ipsilateral low back deep hyperalgesia and superficial mechanical hypersensitivity lasted longer in females compared with males. Moreover, female rats had bilateral deep mechanical hyperalgesia and cutaneous trunk mechanical hypersensitivity, unlike males. Our results are the first to demonstrate that there are sex differences in an animal model of LBP induced by the painful substance NGF. Future studies may help to reveal the underlying biological mechanisms of LBP to create better treatments to attempt to help those suffering with LBP.Low back pain (LBP) is a globally prevalent and costly societal problem with multifactorial etiologies and incompletely understood pathophysiological mechanisms. To address such shortcomings regarding the role of neurotrophins in the underlying mechanisms of pain, an LBP model was developed in rats involving two unilateral intramuscular injections of nerve growth factor (NGF) into deep trunk muscles. To date, behavioral investigations of this NGF-LBP model have been limited, especially as it pertains to female pain behaviors. This study compared mechanical sensitivity to noxious (hyperalgesia) and non-noxious (hypersensitivity) stimuli in control and NGF-injected male and female rats through pain resolution. Although the baseline testing revealed no differences between males and females, NGF-injected females demonstrated prolonged ipsilateral deep trunk mechanical hyperalgesia that resolved seven days later than males. Moreover, females showed bilateral trunk mechanical sensitivity to noxious and non-noxious stimuli compared to only ipsilateral behaviors in males. Sex differences were also observed in the severity of behavioral responses, with females displaying greater mean differences from baseline at several timepoints. Overall, these NGF-LBP behavioral findings mirror some of the sex differences reported in the clinical presentation of LBP and accentuate the translatability of this NGF-LBP model. Future studies using this LBP-NGF model could help to elucidate the neurobiological mechanisms responsible for the development, severity, and/or resolution of muscular LBP as well as to provide insights into the processes governing the transition from acute to chronic LBP.