A Study Of Age-related Change In Pain Sensitivity

The individual adult shows a gradual decline in functional ability with the advancing age, which is referred to as aging process. In the process, age-related change in the sensori-motor ability is displayed due to age-related change in functions and structures of nervous system (Gagliese, 1999a; Hedden, 2004; Melcangi, 2000; Rutten, 2003; Verdu, 2000). Clinically, the pain complaints increase with advancing age. And aged people show the change in pain perception. To explore whether there is an age-related change in pain sensitivity, and if any what are the neurobiological mechanisms underlying the potential age-related change, we measure the pain sensitivity of three age groups (Young, 2-3m; Mid-aged, 17-19m; Aged, 24~26m) of rats under both non-inflamed and inflamed conditions. As behavioral manifestations of pain consist of persistent spontaneous nociception, thermal and mechanical hypersensitivity and inflammatory responses under the conditions with peripheral inflammation, we investigated respectively the effect of aging on different kinds of behavioral manifestations of pain in our experiments. The results are as follows:Results:1. The effect of aging on pain sensitivity of rats under either non-inflamed or inflamed conditions.1.1. The effect of aging on pain sensitivity under non-inflamed conditionsUnder non-inflamed conditions, baseline PWTL and PWMT of each rat of three age groups were measured. Although the baseline PWTL did not significantly change with the advancing age, the baseline PWTL of aged rats was a little lower than young and mid-aged rats. Although there was no significant difference, there was an age-related tendency of decline in the baseline PWMT.1.2. The effect of aging on pain sensitivity under inflamed conditions1.2.1 PSNSubcutaneous injection of BV could induce persistent spontaneous nociception. In our experiments, we counted the number of withdrawal reflexes, the total time of licking and lifting and the scores of pain intensity in every 5 minutes of 1 hour after BV treatment.There was a tendency of age-related decline in both the number of spontaneous withdrawal reflex in every 5 minutes of 1 hour and the total number in 1 hour. The total number of aged rats was significantly fewer than young cohorts.The total time of licking & lifting displayed an age-related decrease. However, the decrease is not statistically significant.And there was no significant change in mean pain intensity scores within three age groups of rats.1.2.2 Thermal and mechanical hypersensitivity4 hours after BV treatment, PWTL and PWMT in the injection site were measured. The results implied the presence of thermal and mechanical hypersensitivity in all three age groups of inflamed rats. Under inflamed conditions, the decrease of PWTL of young rats was more significant than aged cohorts. However, there was no age-related difference in PWMT after BV treatment.1.2.3 Inflammatory responses4 hours after BV treatment, the change of the injected hindpaw in the volume and the optical density of Evens blue were measured to quantify the edema and inflammatory extravasations respectively. The results implied that BV injection could induce significant inflammatory responses in injected hindpaw of each rat of three age groups, and that aged rats showed lower inflammatory responses in both edema and inflammatory extravasations than young and mid-aged cohorts. The latter two age groups didn't show significant difference in inflammatory responses. 2 The neurobiological mechanisms underlying age-related changein the sensitivity to thermalgesia. 2.1 The effect of aging on the level of thermal nociceptor (TRPV1)in spinal dorsal hornTRPV1 is a nonseletive cation channel identified as a thermal nociceptor. It is mainly expressed in small-to-medium-diameter neurons in DRG and could be found in the peripheral and central terminals (Caterina, 1997; Tominaga, 1998). The innervated area of TRPV1 -labeled terminals and the intensity of TRPVl-like immunoreactivity in the spinal cord...