Neuroscience letters
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Neuroscience letters · Jul 2009
Involvement of increased expression of transient receptor potential melastatin 8 in oxaliplatin-induced cold allodynia in mice.
Oxaliplatin is a chemotherapy drug and induces peripheral neuropathy which is aggravated by exposure to cold, the mechanism of which is unclear. In the present study, we investigated in mice whether transient receptor potential melastatin 8 (TRPM8), which is activated by cooling temperature, would be involved in cold allodynia induced by oxaliplatin. Mice were given an intraperitoneal injection of oxaliplatin. ⋯ Oxaliplatin increased wet-dog shake and jumping behaviors evoked by the TRPM8 agonist icilin. An injection of oxaliplatin increased the expression level of TRPM8 mRNA at day 3 after injection and the expression was decreased to the near-normal level on days 10 and 25. These results suggest that cold allodynia induced by oxaliplatin is at least partly due to the increased expression of TRPM8 in the primary afferents.
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Neuroscience letters · Jul 2009
Chronic nicotine exposure inhibits 17beta-estradiol-mediated protection of the hippocampal CA1 region against cerebral ischemia in female rats.
Nicotine addiction in women increases the risk of ischemic stroke. Importantly, women who smoke and use hormone replacement therapy/oral contraceptives greatly increase their risk of coronary heart disease and ischemic stroke as compared to nonsmoking women who use occasionally oral contraceptives. Nicotine addiction disturbs the normal periodicity of the menstrual cycle and induces early onset of menopause in women; however, the mechanism of the synergistic effects of nicotine and sex hormones on cerebrovascular health is not clearly understood. ⋯ Our results demonstrated that chronic nicotine exposure followed by ischemic insult at the proestrus stage of the estrous cycle showed that only 14% of normal neurons remained compared to the non-nicotine-treated group (p<0.05). Similarly, a bolus of 17beta-estradiol to nicotine-treated ovariectomized rats showed only 26% of normal neurons remaining as against 47% in the non-nicotine-treated group. Nicotine exposure decreased ERbeta but not ERalpha protein levels in the hippocampus, suggesting a role for ERbeta in increased post-ischemic neurodegeneration from nicotine exposure.
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Neuroscience letters · Jul 2009
Role of ET(A) and ET(B) endothelin receptors on endothelin-1-induced potentiation of nociceptive and thermal hyperalgesic responses evoked by capsaicin in rats.
Increasing evidence indicates that endothelin-1 (ET-1) activates nociceptive neurons and sensitizes them to different noxious stimuli, but involvement of TRPV1-dependent mechanisms in mediation of such effects is not yet fully understood. Here we report that intraplantar (i.pl.) injection of ET-1 (10 pmol) into the hind paw of rats induced overt nociceptive behavior over the first hour, followed by a slowly developing thermal hyperalgesia, lasting from 3 to 8h after injection. Both effects were also induced by similar injections of capsaicin (10-1000 pmol), but these responses were shorter lasting than those caused by ET-1. ⋯ The potentiation of capsaicin-induced nociception by ET-1 was abolished by prior i.pl. injection of BQ-123 (ET(A) receptor antagonist, 10 nmol), but unaffected by BQ-788 (ET(B) receptors antagonist, 10 nmol), whereas the enhancement of capsaicin-induced hyperalgesia by ET-1 was attenuated by both antagonists. Therefore, differently to what has been reported in mice, in rats TRPV1 receptors contribute selectively to thermal hyperalgesia, but not overt nociception, induced by ET-1. Importantly, although ET-1 augments capsaicin-induced overt nociception and thermal hyperalgesia, potentiation of the former relies solely on ET(A) receptor-mediated signaling mechanisms, whereas both receptors contribute to the latter.
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Neuroscience letters · Jul 2009
Increased glutamate and decreased glycine release in the rostral ventromedial medulla during induction of a pre-clinical model of chronic widespread muscle pain.
Two injections of acidic saline into the gastrocnemius muscle produce long-lasting hyperalgesia that is initiated and maintained by changes in the rostroventromedial medulla (RVM). Potential underlying mechanisms could be increased release of excitatory neurotransmitters and/or reduced release of inhibitory neurotransmitters, in the RVM. We tested this hypothesis by measuring concentrations of aspartate, glutamate and glycine in response to the first and second injection of acidic saline and compared to intramuscular injections of normal saline using microdialysis with HPLC analysis. ⋯ There were also long-lasting decreases in glycine concentrations in the RVM in response to both the first and second injection of acidic saline. It is possible that disinhibition after the first injection leads to long-lasting neuronal changes that allow a greater release of excitatory neurotransmitters after the second injection. We hypothesize that increased release of excitatory neurotransmitters in the RVM drives the release of excitatory neurotransmitters in the spinal cord, central sensitization and the consequent hyperalgesia.