| Recently, clinical and basic experimental studies have shown that human or rodent neonates experiencing nociceptive stimulation may have an altered pain perception, thus the insight into the molecular and cellular biology of fetal or neonatal pain has important clinical implications. Although there are lines of clinical and basic evidence showing altered pain behaviors and spinal structural plastic changes, the following issues are not clear and should be addressed: (1) Do the neonatally persistent nociceptive stimuli cause a similar effects on different types of pathological pain in mature individual such as persistent spontaneous pain, primary and secondary hyperalgesia, or heat and mechanical hyperalgesia ? (2) Are the expressions of mature spinal neurotrophins and their high affinity receptors (NGF, nerve growth factor/TrkA, BDNF, brain-derived neurotrophic factor/TrkB), cytokines such as IL-lp (interleukin IP) and inducible prostaglandin-producing limited enzymes COX2 (cyclooxygenase 2) affected by neonatally persistent nociceptive stimuli ? To answer the above two questions, the bee venom test that is ableto show multiplicity of pathological pain and immunohistochemistry were used hi the present study.Postnatal age-related changes in baseline PWTL and PWMT, and peripherally chemical injury-induced persistent spontaneous nociception and heat or mechanical hyperalgesia(1) Rats with postnatal age of PI, P4, P7, P14, P21 and P28 show distinct age-related changes in baseline PWTL (paw withdrawal thermal latency) and PWMT (paw withdrawal mechanical threshold). Neonatal rats show the lowerest baseline PWTL at PI, reach maxiaml at P7 and remain stable from P7 to P28; however, the baseline PWMT was remained extremely lower stable value between PI-21 and increased afterward through the remaining life. The baseline PWMT at P28 was 10 fold of that at P1 -21.(2) Postnatal rats receiving peripheral chemical injury (s.c. intraplantar BV injection) showed a dose-related increase in persistent paw flinching reflex from P1-P28 and the time course response pattern was similar to that observed in the adult rats.(3) Postnatal rats receiving the same peripheral chemical injury showed non-specific heat pain hypersensitivity before PI4, because either postnatal non-nociceptive (saline) or nociceptive (BV) stimuli cause a parallel reduction in PWTL between PI-14; but the heat pain hypersensitiviry became specific since P14 age. Rats receiving the same two treatments also showed non-specific mechanical hypersensitivity before P21, but the mechanical hypersensitivity became specific since P21.Effects of postnatally peripheral chemical injury on the baseline PWTL and PWMT, and injury-induced persistent nociception and hyperalgesia(1) Mature rats which receiving neonatally nociceptive stimuli showed no difference in baseline PWTL when compared with those rats receiving non-nociceptive stimuli (P>0.05), however the mature baseline PWMT was significantly decreased by postnatal nociceptive stimuli before age P21 (P<0.01).(2) Postnatally peripheral chemical injury enhanced the intensity of persistent spontaneous nociceptive response induced by the same injury-treatment in mature rats.(3) Time course (2, 4, 8, 24, 48, 72, 96 h after peripheral tissue injury) observations showed that the tissue injury-induced heat hyperalgesia in mature rats was not changed by either postnatal nociceptive or non-nociceptive stimuli, however, the mechanical hyperalgesia in the mature rats was completely abolished by postnatal BV-induced tissue injury at age between P4-21. In contrast, postnatal peripheral tissue injury treatment at age > P21 could enhance the mechanical hyperalgesia in mature rats.Effects of neonatal peripheral tissue injury on pain-related behaviors in male and female mature rats(1) Postnatal peripheral tissue injury at different age (PI, 4, 7, 14, 21, 28) did not affect baseline PWTL in the mature rats and no significant statistical difference was found between male and female r...
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