疼痛的性别差异

目前已有许多临床流行病学研究和实验研究证实了人类的疼痛存在性别差异。临床迹象表明疼痛存在性别差异,许多慢性疼痛疾病（偏头痛、颞下颌关节痛、纤维肌痛、风湿痛等）的发生率女性明显高于男性。女性对一些实验性疼痛（机械刺激痛、电刺激痛、热刺激痛等）更加敏感,痛阈和对疼痛的耐受性比男性低,而且女性月经周期与疼痛有关。啮齿动物实验研究也发现存在疼痛的性别差异。但是在不同动物研究或不同实验性疼痛刺激下雌雄性别的反应不完全相同,这些差异可能是由很多影响因素所导致的。目前许多研究对疼痛存在性别差异的解释也有所不同,机制尚不清楚,可能的因素包括：生物因素（性激素、内源性镇痛、基因等）、社会心理因素以及两者的相互作用等。     

疼痛的性别差异

目前已有许多临床流行病学研究和实验研究证实了人类的疼痛存在性别差异.临床迹象表明疼痛存在性别差异,许多慢性疼痛疾病(偏头痛、颞下颌关节痛、纤维肌痛、风湿痛等)的发生率女性明显高于男性.女性对一些实验性疼痛(机械刺激痛、电刺激痛、热刺激痛等)更加敏感,痛阈和对疼痛的耐受性比男性低,而且女性月经周期与疼痛有关.啮齿动物实验研究也发现存在疼痛的性别差异.但是在不同动物研究或不同实验性疼痛刺激下雌雄性别的反应不完全相同,这些差异可能是由很多影响因素所导致的.目前许多研究对疼痛存在性别差异的解释也有所不同,机制尚不清楚,可能的因素包括:生物因素(性激素、内源性镇痛、基因等)、社会心理因素以及两者的相互作用等.     

Biological time-dependent difference in effect of peroxynitrite demonstrated by the mouse hot plate pain model

We previously demonstrated the rhythmic pattern of L-arginine/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) cascade in nociceptive processes. The coupled production of excess NO and superoxide leads to the formation of an unstable intermediate peroxynitrite, which is primarily responsible for NO-mediated toxicity. In the present study, we evaluated the biological time-dependent effects of exogenously administered peroxynitrite on nociceptive processes and peroxynitrite-induced changes in the analgesic effect of morphine using the mouse hot-plate pain model. Experiments were performed at four different times of day (1, 7, 13, and 19 hours after lights on, i.e., HALO) in mice of both sexes synchronized to a 12 h:12 h light-dark cycle. Animals were injected intraperitoneally (i.p.) with saline or 10 mg/kg morphine 30 min before and 0.001 mg/kg peroxynitrite 30 sec before hot-plate testing, respectively. The analgesic effect of morphine exhibited significant biological time-dependent differences in the thermally-induced algesia; whereas, administration of peroxynitrite alone exhibited either significant algesic or analgesic effect, depending on the circadian time of its injection. Concomitant administration of peroxynitrite and morphine reduced morphine-induced analgesia at three of the four different study time points. In conclusion, peroxynitrite displayed nociceptive and antinociceptive when administered alone according to the circadian time of treatment, while it diminished analgesic activity when administered in combination with morphine at certain biological times.     

Decreased odontometric sex difference in individuals with dental agenesis

Partial Dental Agenesis has been shown related to decreased mesiodistal tooth size. The sexual difference in permanent tooth size of 104 normal individuals with congenital absence of one or more secondary teeth has been studied. Males are observed to have more mesiodistal size reduction than females. In only two of 14 tooth types examined was a statistical sex difference in mesiodistal size shown. It is of interest that each of these was in the canine field area. A sex difference was slightly more apparent when studying the buccolingual dimension; however, several difficulties were encountered in obtaining measurements in this diameter.     

Confirmation of the sex difference in continuing subperiosteal apposition

A major sex difference in the rate of continuing bone expansion was confirmed for 5660 adult subjects of European ancestry. The five-decade gain in metacarpal midshaft area amounted to 8.4% in 3455 females and 2.8% in 2205 males. There was no systematic age effect on the length of the second metacarpal. Accordingly, both bone expansion and the marked sex difference in its magnitude may be attributed to sex-specific aspects of ageing much like the sex difference in endosteal surface loss.     

A sex difference in the context-sensitivity of dominance perceptions

Although dominance perceptions are thought to be important for effective social interaction, their primary function is unclear. One possibility is that they simply function to identify individuals who are capable of inflicting substantial physical harm, so that the perceiver can respond to them in ways that maximize their own physical safety. Another possibility is that they are more specialized, functioning primarily to facilitate effective direct (i.e., violent) intrasexual competition for mates, particularly among men. Here we used a priming paradigm to investigate these two possibilities. Facial cues of dominance were more salient to women after they had been primed with images of angry men, a manipulation known to activate particularly strong self-protection motivations, than after they had been primed with images of angry women or smiling individuals of either sex. By contrast, dominance cues were more salient to men after they had been primed with images of women than when they had been primed with images of men (regardless of the emotional expressions displayed), a manipulation previously shown to alter men's impressions of the sex ratio of the local population. Thus, men's dominance perceptions appear to be specialized for effective direct competition for mates, while women's dominance perceptions may function to maximize their physical safety more generally. Together, our results suggest that men's and women's dominance perceptions show different patterns of context-sensitivity and, potentially, shed new light on the routes through which violence and intrasexual competition have shaped dominance perceptions.     

Characterization of the G-protein-coupled membrane-bound estrogen receptor GPR30 in the zebra finch brain reveals a sex difference in gene and protein expression

Estradiol‐induced structural dimorphisms exist in the songbird brain. However, how they arise is not clear since there is a scarce distribution of ERα and lack of ERβ in song control nuclei. This suggests that other receptors are involved. The G‐protein coupled membrane‐bound estrogen receptor, GPR30, is a candidate but has never been investigated in songbirds. In this study, we characterized its gene and protein in the zebra finch brain. Analysis of the putative GPR30 protein sequence revealed a strong similarity to avian and mammalian homologues. Quantitative PCR indicated that the gene was elevated in the telencephalon of both sexes from posthatching day (P) 15 to P45, with a male‐biased sex difference at P21 and P30. In comparison, expression at younger posthatching ages and in adults was significantly less. At P21, GRP30 protein was widespread, nonuniform, and overlapped with song control nuclei. Of particular interest, the number of immunoreactive cells was greatest in HVC and RA, but less in LMAN and Area X. Labeling in HVC was also dimorphic; with more cells present in males than in females. In parallel with the gene, by adulthood, protein expression was reduced across most brain regions. Taken together these data suggest that GPR30 may contribute to differences in song system development by mediating dimorphic responses to estrogens. In addition, the extensive protein distribution indicates that it may also have a role in general brain development in both sexes. © 2011 Wiley Periodicals, Inc. Develop Neurobiol, 2012     

Minimizing variables among hairpin-based RNAi vectors reveals the potency of shRNAs

RNA interference (RNAi) is a cellular process regulating gene expression and participating in innate defense in many organisms. RNAi has also been utilized as a tool to query gene function and is being developed as a therapeutic strategy for several diseases. Synthetic small interfering (siRNAs) or expressed stem–loop RNAs (short-hairpin RNAs [shRNAs] or artificial microRNAs [miRNAs]) have been delivered to cultured cells and organisms to inhibit expression of a variety of genes. A persistent question in the field, however, is which RNAi expression system is most suitable for distinct applications. To date, shRNA- and artificial miRNA-based strategies have been compared with conflicting results. In prior comparisons, sequences required for efficient RNAi processing and loading of the intended antisense strand into the RNAi-induced silencing complex (RISC) were not considered. We therefore revisited the shRNA–miRNA comparison question. Initially, we developed an improved artificial miRNA vector and confirmed the optimal shRNA configuration by altering structural features of these RNAi substrates. Subsequently, we engineered and compared shRNA- and miRNA-based RNAi expression vectors that would be processed to yield similar siRNAs that exhibit comparable strand biasing. Our results demonstrate that when comparison variables are minimized, the shRNAs tested were more potent than the artificial miRNAs in mediating gene silencing independent of target sequence and experimental setting (in vitro and in vivo). In addition, we show that shRNAs are expressed at considerably higher levels relative to artificial miRNAs, thus providing mechanistic insight to explain their increased potency.     

The sex difference in dimensional communalities in Macaca nemestrina.

Intr-individual correlations for cranial, mandibular and dental measurements made on lateral skull radiographs of Macaca nemestrina were systematically higher in 30 adult females than in 31 adult males by an average of 0.11 to 0.15, depending upon method of computation. Clearly, for the adult pig-tailed monkey as in Homo during both prenatal and postnatal life, developmental and dimensional communalities are systematically higher in the female indicating a general principle or trend.     

Evidence for role of endogenous sex steroids in morphine antinociception.

The effect of morphine on responses to sustained mild pain was tested in male white rats with gonads and (or) adrenals removed. Morphine was ineffective in gonadectomized rats; adrenalectomy alone increased the effectiveness of morphine over that in sham-operated controls. Morphine antinociception may involve some actions of endogenous steroids.     

A single dose of liposome-encapsulated oxymorphone or morphine provides long-term analgesia in an animal model of neuropathic pain

An extended-release formulation of oxymorphone was produced by encapsulation into liposomes, using a novel technique. Liposome-encapsulated morphine was produced, using a standard technique These preparations were tested in an animal model of neuropathic pain. Male Sprague-Dawley rats (approx. 300 g) were allotted to control (non-loaded liposomes) and treatment (liposome-encapsulated oxymorphone or morphine) groups. Drugs were administered subcutaneously to all rats immediately prior to sciatic nerve ligation. Thermal withdrawal latencies were measured at baseline and daily for seven days after sciatic nerve ligation. A second experiment involved subcutaneous administration of non-loaded liposomes, morphine, or oxymorphone to rats that did not undergo sciatic nerve ligation. Thermal withdrawal latencies in sciatic nerve-ligated rats given non-loaded liposomes decreased significantly by day four, with maximal decrease at day seven after surgery, indicating development of full hyperalgesia. In contrast, ligated rats given liposome-encapsulated morphine or liposome-encapsulated oxymorphone had no decrease in thermal withdrawal latency by day four, indicating that these long-acting preparations prevented development of hyperalgesia after a single injection. This treatment effect persisted to day seven. Non-ligated rats treated with vehicle or liposome-encapsulated morphine had no change in thermal withdrawal latencies. Non-ligated rats treated with liposome-encapsulated oxymorphone had a small, but significant increase in thermal withdrawal latency from day four through day seven. One subcutaneous injection of liposome-encapsulated oxymorphone or morphine was effective in preventing hyperalgesia in this pain model for up to seven days. These results suggest that liposome-encapsulation of oxymorphone offers a novel, convenient, and effective means to provide long-term analgesia.     

Control of severe pain with sustained-release morphine tablets v. oral morphine solution.

Recently a sustained-release morphine sulfate tablet (MS Contin [MSC]) was introduced in Canada. In a randomized double-blind crossover trial we compared MSC given every 12 hours with a morphine sulfate solution (MSS) given every 4 hours to 17 patients suffering from chronic severe pain. After titration of the morphine dosage to optimize the analgesic effect, each patient received 10 days of therapy with either MSC or MSS, then 10 days of therapy with an equal daily dose of the other formulation. Both preparations provided effective pain control, with minimal side effects. There was no significant difference between MSC and MSS in pain scores on a visual analogue scale (VAS), severity scores for tiredness and nausea, amount of supplemental morphine needed for break-through pain or patient preference. The plasma morphine concentrations tended to be greater during treatment with MSC. The study had an 89% probability of detecting a clinically significant difference in VAS pain scores. We conclude that an individualized, twice-daily regimen of MSC is as effective as MSS given every 4 hours for control of severe pain. The twice-daily regimen has several advantages: it provides for an uninterrupted night''s sleep, it is substantially more convenient than the six doses per day required with MSS, and it should help reduce both medication errors and noncompliance.     

Upregulation of opioid receptor subtypes correlates with potency changes of morphine and DADLE

Chronic treatment with opioid antagonists increases the potency of opioid agonists and produces an increase in brain opioid binding sites. In the present study, 8 day treatment with naltrexone blocked morphine and DADLE analgesia for the entire treatment period and increased mu 1, mu 2 and delta opioid receptor binding sites in mouse brain. mu 1 and mu 2 binding were increased by 81 and 67%, respectively, while delta binding was increased by 31%. Consistent with these binding changes, the potency of ICV morphine to produce analgesia was increased by over 3-fold, while the potency of ICV DADLE was increased by only 1.7. These findings indicate that relative increases in opioid receptor subtypes agree with pharmacodynamic studies on potency changes of opioid agonists.     

Normal haematological values: sex difference in neutrophil count.

Blood counts were performed on 100 male and 100 female staff to establish normal ranges for our hospital. Neutrophil counts were found to be on average 0.66 times 10-9/1 (660/mm-3) higher in women than in men. Statistically this difference was highly significant and was not due to the fact that many of the women were taking oral contraceptives. The neutrophil counts of the men and women were also on average 0.50 times 10-9/1 (500/mm-3) greater in the afternoon than in the morning. A correlation was observed between the neutrpphil and the monocyte counts.