Changes in spinal serotonin turnover mediate age-related differences in the behavioral manifestations of peripheral nerve injury

The Bennett and Xie model of peripheral nerve injury was used to study the effects of aging on the onset and progression of sciatic nerve ligation (SN L)-induced thermal hyperalgesia and tactile-evoked allodynia in young, matu re, and aged Fischer 344 FBNF1 male rats (4-6, 14-16, and 24-26 months old, respectively). A plantar analgesia meter and calibrated von Frey pressure filaments were employed as the analgesiometric assays. In the absence of ne rve injury, aged rats were found to be more sensitive than younger animals to noxious thermal stimuli. Following the SNL surgery, thermal hyperalgesia was observed in all three age groups within 3 days. On post-SNL day 35, th e paw-withdrawal latency values of the young and mature animals returned to presurgical baseline levels, while the aged rats continued to exhibit ther mal hyperalgesia. Tactile-evoked allodynia was apparent within 3 days follo wing peripheral nerve injury in the oldest cohort, but was delayed in the y ounger animals. On post-SNL days 0 (control), 3, 21, and 35, young, mature, and aged rats were sacrificed and high-performance liquid chromatography a nd electrochemical detection (HPLC/ECD) methods were used for neurochemical analyses of spinal serotonin (5-HT), norepinephrine (NE), and 5-hydroxyind oleacetic acid (5-HIAA). Spinal 5-HT and NE levels were not significantly a ltered by the aging process, nor were they affected by peripheral nerve inj ury. However, spinal 5-HT turnover from the aged animals was greater than t hat detected in spinal tissue from the younger counterparts. Differences in spinal 5-HT turnover may contribute to age-related variability in spinal n ociceptive processing. (C) 2000 Elsevier Science Inc.