| There is increasing line of evidence showing that experimental, acute and chronic pain will differ with increase in age. Unfortunately, knowledge about the characteristics and the underlying mechanisms of elderly pain is poorly understood. To see insight into this question, the following issues were studied in the present experiment: (1) Two animal models of persistent pain were selected: one is the formalin (F) test in which two phases of spontaneous pain-related responses can be steadily induced; the other is the bee venom (BV) test in which one phase of spontaneous pain-related responses and hyperalgesia can be steadily induced. The BV and F-induced persistent spontaneous nociception (PSN) and hyperalgesia were compared in elderly rats; (2) Laminar distribution and time course of the BV-induced c-Fos protein expression in the spinal cord of elderly rats were observed; (3) Sensitivity of the BV-induced hyperalgesia to systemic application of glutamate NMDA receptor antagonist, MK-801, or u-opioid receptor agonist, morphine inelderly rats were analysed.1 Pain-related behavioral response of elderly rats: the BY test versus formalin testDifferent noxious chemical agent (50 ul of 2.5% formalin or 0.4% bee venom) was administered into the plantar surface of one hindpaw of the aged rat (age>20 months). By using quantitative measurements for persistent spontaneous paw flinching reflex (PSFR), lifting and licking time (L<), paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT), time course and response characteristics of the persistent spontaneous pain (PSN) and hyperalgesia of elderly and adult young rats were compared.?The elderly rats receiving s.c. BV or F could also express PSN, but there are differences when quantified by counting the spinally organized persistent spontaneous flinching reflex (PSFR) and supra-spinally organized lifting and licking time (L<). In elderly rats, the total number of the BV-induced PSFR was significantly increased and the peak response was delayed about 30 min after injection when compared with adult young rats. The response pattern and time course of the F-induced PSFR in elderly rats were similar to those of adult young rats, however, the number of PSFR in phase 2 of F response was significantly decreased in elderly rats. In contrast, the BV-induced supra-spinally organized lifting and licking behaviors in elderly rats were similar to those hi adult rats and reached peak timing immediately after s.c. BV injection. However, the time that elderly rats spent at each 5 min interval was increased to 2-3 fold of that spent by adult rats during the whole 1.5 h time course. (2) The elderly rats showed a significant increase in baseline PWTL and PWMT compared with the adult young rats. (3) Intraplantar F injection in elderly rats was not able to induce decrease in PWTL andPWMT, reversely, it resulted in an increase hi PWTL and PWMT or loss of sensory response to high intensity stimuli. (4) Intraplantar BV injection in elderly rats, however, was able to induce decrease in both PWTL and PWMT in the injured region lasting for several days and the duration for PWMT was significant longer than that for PWTL.2 Laminar distribution and time course of the BV-induced c-Fos protein expression in the spinal cord of elderly ratsImmunostaining of c-Fos protein in the lumbar spinal cord was carried out in urethane-anesthetized elderly rats 2 h, 1 week and 2 month after BV injection or after saline. Three time points were selected, because heat and mechanical hyperalgesia were significiant 2 h after BV, only mechanical hyperalgesia existed 1 week after BV and neither heat nor mechanical hyperalgesia was existed 2 month after BV.Proportiontal rate of bv-induced c-Fos expression in the superficial layers to total c-Fos expression of the spinal dorsal horn was largely reduced with disappearance of heat hyperalgesia, while c-Fos expression in deep layers was increased with existence of mechanical hyperalgesia until 1 week after BV. Expre...
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