Influence of traumatic impaction and pathological loading on knee menisci

Nearly half of the US population faces the risk of developing knee osteoarthritis (OA). Both in vitro and in vivo studies can aid in a better understanding of the etiology, progression, and advancement of this debilitating disorder. The knee menisci are fibrocartilagenous structures that aid in the distribution of load, attenuation of shock, alignment and lubrication of the knee. Little is known about the biochemical and morphological changes associated with knee menisci following altered loading and traumatic impaction, and investigations are needed to further elucidate how degradation of this soft tissue advances over time. The biochemical response of porcine meniscal explants was investigated following a single bout of dynamic compression with and without the treatment of the pharmaceutical drug, anakinra (IL-1RA). Dynamic loading led to a strain-dependent response in both anabolic and catabolic gene expression of meniscal explants. By inhibiting the Interleukin-1 pathway with IL-1RA, a marked decrease in several catabolic molecules was found. From these studies, future developments in OA treatments may be developed. The implementation of an in vivo animal model contributes to the understanding of how the knee joint behaves as a whole. A novel closed-joint in vivo model that induces anterior cruciate ligament (ACL) rupture has been developed to better understand how traumatic injury leads to OA. The menisci of knees from three different groups (healthy, ACL transected, and traumatically impacted) were characterized using histomorphometry. The acute and chronic changes within the knee following traumatic impaction were investigated. The works presented in this dissertation have focused on the characterization, implementation, and development of mechanically-induced changes to the knee menisci.

Sleep Deprivation and Pain Intensity

Little or poor quality sleep is often reported in patients suffering from acute or chronic pain. Conversely, sleep loss has been known to elevate pain perception; thus a potential bi-direction relationship exists between sleep deprivation and pain. The effect of sleep deprivation on the thermal pain intensity has yet to be determined, furthermore, sex differences in pain have not been examined following sleep deprivation. There is also a higher prevalence of insomnia in women, and reports indicate that sleep quality is diminished and pain sensitivity may be greater during high hormone phases of the menstrual cycle. In Study 1 we examined the effects of 24-hour total sleep deprivation (TSD) on pain intensity during a 2-minute cold pressor test (CPT). We hypothesized that TSD would augment thermal pain intensity during CPT and women would demonstrate an elevated response compare to men. In Study 2 we investigated the effects of menstrual phase on pain intensity during CPT following TSD. We hypothesized that pain intensity would be augmented during the mid-luteal (ML) phase of the menstrual cycle. In Study 1, pain intensity was recorded during CPT in 14 men and 13 women after normal sleep (NS) and TSD. Pain intensity responses during CPT were elevated in both conditions; however, pain intensity was augmented (~ 1.2 a.u.) following TSD. When analyzed for sex differences, pain intensity was not different between men and women in either condition. In Study 2, pain intensity was recorded during CPT in 10 female subjects during the early follicular (EF) and ML phases of the menstrual cycle after TSD. Estradiol and progesterone levels were elevated during the ML phase, however, pain intensity was not different between the two phases. We conclude that TSD significantly augments pain intensity during CPT, but this response is not sex dependent. We further demonstrate that the collective effect of TSD and elevated gonadal hormone concentrations do not result in a differential pain response during the EF and ML phases of the menstrual cycle. Collectively, sleep loss augments pain intensity ratings in men and women and may contribute to sleep loss in painful conditions.