Age-dependent down-regulation of orexin receptors in trigeminal nucleus caudalis correlated with attenuation of orexinergic analgesia in rats.

Aging is related to a variety of physiological organ changes, including central and peripheral nervous systems. It has been reported that the orexin signaling has a potential analgesic effect in different models of pain, especially inflammatory pulpal pain. However, the age-induced alteration in dental pain perception and orexin analgesia has not yet been fully elucidated. Here, we tested that how aging may change the effect of orexin-A on nociceptive behaviors in a rat dental pulp pain model. The expression levels of orexin receptors and the nociceptive neuropeptides substance P (SP) and calcitonin-related gene peptide (CGRP) were also assessed in the trigeminal nucleus caudalis (TNC) of young and aged rats. Dental pulp pain was induced by intradental application of capsaicin (100 µg). The immunofluorescence technique was used to evaluate the expression levels. The results show less efficiency of orexin-A to ameliorate pain perception in aged rats as compared to young rats. In addition, a significant decrease in the number of orexin 1 and 2 receptors was observed in the TNC of aged as compared to young rats. Dental pain-induced SP and CGRP overexpression was also significantly inhibited by orexin-A injection into the TNC of young animals. In contrast, orexin-A could not produce such effects in the aged animals. In conclusion, the older age-related reduction of the antinociceptive effect of orexin may be due to the downregulation of its receptors and inability of orexin signaling to inhibit the expression of nociceptive neuropeptides such as SP and CGRP in aged rats.

Aging exaggerates pulpal pain sensation by increasing the expression levels of nociceptive neuropeptides and inflammatory cytokines.

BACKGROUND: Dental pain is a main clinical problem in the elderly population and its assessment and treatment make special challenges for health care services. However, the age-induced alteration in dental pain perception and the underlying molecular mechanism(s) has not yet been fully clarified. METHODS: Here, the effect of aging on nociceptive behaviors following inflammatory dental pulp pain was evaluated. Since prostaglandins, nociceptive neuropeptides, and inflammatory cytokines have critical roles in the development of aging as well as pain signaling, the expression levels of COX-2, CGRP, IL-1ß, IL-6, TNF-α and its converting enzyme TACE were assessed in the trigeminal ganglion of young and aged rats with dental pain. Dental pulp pain was induced by intradental application of capsaicin (100 µg). The immunofluorescence (COX-2 and CGRP) and western blot techniques were used. RESULTS: The data showed that aged animals have different pattern of pain. So that, the mean of nociceptive scores was significantly greater in aged rats at 10 and 15 min after capsaicin injection. In aged rats, dental pain was persisting over 7 h, while it was disappeared at 300 min in young rats. Molecular data showed that dental pain significantly increased the expression of COX-2, CGRP, IL-1ß, IL-6, TNF-α and TACE in the trigeminal ganglion of the young and aged rats. In addition, the amount of those parameters, except TACE, in capsaicin-treated aged animals were significantly (p < 0.05) greater than those in capsaicin-treated young rats. CONCLUSION: It seems that the induction of pro-inflammatory cytokines in an acute inflammatory pulpal pain model may contribute, at least in part to the increased nociceptive behaviors and pain perception in aged rats.

Ginger Extract Reduces Chronic Morphine-Induced Neuroinflammation and Glial Activation in Nucleus Accumbens of Rats.

BACKGROUND: Chronic usage of morphine elicits the production of inflammatory factors by glial cells and induces neuroinflammation. Ginger (Zingiber Officinale Roscoe) is a medicinal herb that has anti-inflammatory properties. It has been reported that ginger shows anti-addictive effects against chronic usage of morphine; however, its influence on morphine-induced neuroinflammation has not yet been clarified. METHODS: Morphine (12 mg/kg) was administrated intraperitoneally for 6 consecutive days. To evaluate the effect of ginger on morphine-induced neuroinflammation, ginger extract (100 mg/kg) was given orally 30 minutes before morphine. Glial fibrillary acidic protein (GFAP) and p38 mitogen-activated protein kinase (p38 MAPK) levels were assayed by immunoblotting in the rat nucleus accumbens (NAcc). FINDINGS: The injection of chronic morphine increased the levels of proteins involved in neuroinflammation (p38 MAPK and GFAP) in NAcc. Furthermore, the levels of p38 MAPK and GFAP significantly returned to the control levels by ginger extract. CONCLUSION: The results suggest that the ginger extract can reduce morphine-induced neuroinflammation in NAcc.

Ginger (zingiber officinale roscoe) prevents morphine-induced addictive behaviors in conditioned place preference test in rats.

BACKGROUND: Consumption of chronic morphine induces neuro-inflammation and addictive seeking behavior. Ginger (Zingiber Officinale Roscoe), a well-known spice plant, has been used traditionally in the treatment of a wide variety of ailments. It has been shown that ginger has anti-inflammatory, anti-oxidative and antinociceptive properties. However, its influences on morphine-induced addictive behaviors have not yet been clarified. The aim of the present study was the inhibition of exploratory behavior of morphine addiction in the conditioned place preference test in male desert rats through ginger. METHODS: For conditioning to the morphine, the male Wistar rats received morphine (12 mg/kg intraperitoneally or i.p.) for 6 consecutive days and treatment groups were given different doses of ginger (25, 50 and 100 mg/kg intragastrically or i.g.) 30 min before morphine injection. For investigating addictive seeking behavior, conditioned place preference test (CPP) was used. FINDINGS: Our result demonstrated that injection of morphine for 6 days induces dependency to morphine and creates addictive seeking behavior and ginger (100 mg/kg) could decrease time spend in conditioning box (addictive seeking behavior). CONCLUSION: The data indicated that ginger extract has a potential anti-addictive property against chronic usage of morphine.