The journal of pain : official journal of the American Pain Society
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Temporomandibular joint disorders (TMJD) affect women with greater frequency than men, and sex hormones may contribute to this female predominance. Therefore, this study investigated whether estrogen receptor-alpha (XbaI/PvuII) single nucleotide polymorphisms (SNPs) are associated with TMJD in women. DNA was obtained from 200 women with TMJD (100 with chronic pain and 100 with signs of TMJD but no pain) diagnosed according to the Research Diagnostic Criteria for Temporomandibular Disorder (RDC/TMD) and 100 control women without TMJD. Restriction fragment length polymorphisms of polymerase chain reaction products were used to analyze XbaI and PvuII SNPs in DNA fragments. A model directly characterizing specific DNA sequence variants based on the risk haplotypic structure implemented with the EM algorithm was used to analyze the data. The [GC] haplotype of the XbaI locus was significantly more prevalent in both TMJD groups when compared with the control group (P = .0012). Specifically, the [GC] haplotype was more prevalent within the painful TMJD group versus the control group (OR = 3.203, 95% CI = 1.633, 6.284) and in the TMJD no pain versus the control group (OR = 2.51, 95% CI = 1.267, 4.97). In conclusion, the presence of [GC] haplotype in the XbaI locus may increase the susceptibility of women to develop TMJD. ⋯ This study suggests that a polymorphism in the estrogen receptor may increase the risk of women developing temporomandibular joint disorder. This finding may elucidate the interindividual differences in the contribution of estrogen to TMJD, the genetic influences on TMJD predisposition, and may serve as the basis for future treatment tailoring, which could enhance outcomes for these patients.
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Comparative Study
Comparison of oxaliplatin- and cisplatin-induced painful peripheral neuropathy in the rat.
Although platinum-based cancer chemotherapies produce painful peripheral neuropathy as dose-limiting side effects, there are important differences in the pain syndromes produced by members of this class of drugs. In the rat, cisplatin-induced hyperalgesia has latency to onset of 24 to 48 hours, is maximal by 72 to 96 hours, and is attenuated by inhibitors of caspase signaling but not by inhibitors of the mitochondrial electron transport chain (mETC) and antioxidants. In contrast, oxaliplatin-induced mechanical hyperalgesia is already present by 5 minutes and peaks by 20 minutes. Whereas oxaliplatin hyperalgesia persists for weeks, starting around day 10 to 15, its severity decreases to a lower 2nd plateau level. The rapid-onset 1st plateau in oxaliplatin-induced hyperalgesia was characterized by prominent cold allodynia and in contrast to cisplatin was attenuated by inhibitors of the mETC and antioxidants but not inhibitors of caspase signaling. However, tested later during the 2nd plateau, it was characterized by less intense hyperalgesia and no cold allodynia and was attenuated by inhibitors of caspase signaling as well as by inhibitors of the mETC and by antioxidants. ⋯ The findings of this study distinguish between the neuropathic pain syndromes produced by members of a single chemical class of anticancer drugs and suggest that the underlying mechanisms of various forms of peripheral neuropathy may be different. Further, it defines the need for selective therapy for different types of neuropathy.
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Nociceptin/orphanin FQ (N/OFQ) is the endogenous peptide for the NOP receptors. Depending on the doses, intrathecal administration of N/OFQ has dual actions (ie, hyperalgesia and antinociception) in rodents. However, the pharmacological profile of intrathecal N/OFQ is not fully known in primates. The aim of this study was to investigate behavioral effects of intrathecal N/OFQ over a wide dose range and to compare its effects with ligands known to produce hyperalgesia or antinociception in monkeys. Intrathecal N/OFQ from 1 fmol to 1 nmol did not produce any hyperalgesic or scratching responses. In contrast, intrathecal substance P 100 nmol produced hyperalgesia, and intrathecal DAMGO 10 nmol produced antinociception. At the dose range between 10 nmol and 1 micromol, intrathecal N/OFQ dose-dependently produced thermal antinociception against a noxious stimulus in 2 intensities. More importantly, N/OFQ in combined with intrathecal morphine dose-dependently potentiated morphine-induced antinociception without inhibiting morphine-induced itch/scratching. Taken together, this study is the first to provide a unique functional profile of intrathecal N/OFQ over a wide dose range in primates. Intrathecal N/OFQ produces thermal antinociception without anti-morphine actions or scratching responses, indicating that N/OFQ or NOP receptor agonists represent a promising target as spinal analgesics. ⋯ Intrathecal administration of N/OFQ only produced thermal antinociception, not hyperalgesia, in monkeys. In addition, intrathecal N/OFQ does not have anti-morphine actions or itch/scratching responses. This study strongly supports the therapeutic potential of N/OFQ or NOP receptor agonists as spinal analgesics for clinical trials.