Progesterone and Allopregnanolone Rapidly Attenuate Estrogen-Associated Mechanical Allodynia in Rats with Persistent Temporomandibular Joint Inflammation.

Temporomandibular joint disorder (TMD) is associated with pain in the joint (temporomandibular joint, TMJ) and muscles involved in mastication. TMD pain dissipates following menopause but returns in some women undergoing estrogen replacement therapy. Progesterone has both anti-inflammatory and antinociceptive properties, while estrogen's effects on nociception are variable and highly dependent on both natural hormone fluctuations and estrogen dosage during pharmacological treatments, with high doses increasing pain. Allopregnanolone, a progesterone metabolite and positive allosteric modulator of the GABAA receptor, also has antinociceptive properties. While progesterone and allopregnanolone are antinociceptive, their effect on estrogen-exacerbated TMD pain has not been determined. We hypothesized that removing the source of endogenous ovarian hormones would reduce inflammatory allodynia in the TMJ of rats and both progesterone and allopregnanolone would attenuate the estrogen-provoked return of allodynia. Baseline mechanical sensitivity was measured in female Sprague-Dawley rats (150-175 g) using the von Frey filament method followed by a unilateral injection of complete Freund's adjuvant (CFA) into the TMJ. Mechanical allodynia was confirmed 24 h later; then rats were ovariectomized or received sham surgery. Two weeks later, allodynia was reassessed and rats received one of the following subcutaneous hormone treatments over 5 days: a daily pharmacological dose of estradiol benzoate (E2; 50 µg/kg), daily E2 and pharmacological to sub-physiological doses of progesterone (P4; 16 mg/kg, 16 µg/kg, or 16 ng/kg), E2 daily and interrupted P4 given every other day, daily P4, or daily vehicle control. A separate group of animals received allopregnanolone (0.16 mg/kg) instead of P4. Allodynia was reassessed 1 h following injections. Here, we report that CFA-evoked mechanical allodynia was attenuated following ovariectomy and daily high E2 treatment triggered the return of allodynia, which was rapidly attenuated when P4 was also administered either daily or every other day. Allopregnanolone treatment, whether daily or every other day, also attenuated estrogen-exacerbated allodynia within 1 h of treatment, but only on the first treatment day. These data indicate that when gonadal hormone levels have diminished, treatment with a lower dose of progesterone may be effective at rapidly reducing the estrogen-evoked recurrence of inflammatory mechanical allodynia in the TMJ.

Wearable positive end-expiratory pressure valve improves exercise performance.

We tested a PEEP (4.2 cmH2O) mouthpiece (PMP) on maximal cycling performance in healthy adults. Experiment-1, PMP vs. non-PMP mouthpiece (CON) [n  = 9 (5♂), Age = 30 ±â€¯2 yr]; Experiment-2, PMP vs. no mouthpiece (NMP) [n = 10 (7♂), Age = 27 ±â€¯1 yr]. At timepoint 1 in both experiments (mouthpiece condition randomized) subjects performed graded cycling testing (GXT) (Corival® cycle ergometer) to determine V ˙ O2peak (ml∗kg∗min -1), O2pulse (mlO2∗bt -1), GXT endurance time (GXT-T(s)), and V ˙ O2(ml∗kg∗min -1)-at-ventilatory-threshold ( V ˙ O2 @VT). At timepoint 2 72 h later, subjects completed a ventilatory-threshold-endurance-ride [VTER(s)] timed to exhaustion at V ˙ O2 @VT power (W). One week later at timepoints 3 and 4 (time-of-day controlled), subjects repeated testing protocols under the alternate mouthpiece condition. Selected results (paired T-test, p<0.05): Experiment 1 PMP vs. CON, respectively: V ˙ O2peak â€‹= â€‹45.2 â€‹± â€‹2.4 vs. 42.4 â€‹± â€‹2.3 p<0.05; V ˙ O2@VT â€‹= â€‹33.7 â€‹± â€‹2.0 vs. 32.3 â€‹± â€‹1.6; GXT-TTE â€‹= â€‹521.7 â€‹± â€‹73.4 vs. 495.3 â€‹± â€‹72.8 (p<0.05); VTER â€‹= â€‹846.2 â€‹± â€‹166.0 vs. 743.1 â€‹± â€‹124.7; O2pulse â€‹= â€‹24.5 â€‹± â€‹1.4 vs. 23.1 â€‹± â€‹1.3 (p<0.05). Experiment 2 PMP vs. NMP, respectively: V ˙ O2peak â€‹= â€‹43.3 â€‹± â€‹1.6 vs. 41.7 â€‹± â€‹1.6 (p<0.05); V ˙ O2@VT â€‹= â€‹31.1 â€‹± â€‹1.2 vs. 29.1 â€‹± â€‹1.3 (p<0.05); GXT-TTE â€‹= â€‹511.7 â€‹± â€‹49.6 vs. 486.4 â€‹± â€‹49.6 (p<0.05); VTER 872.4 â€‹± â€‹134.0 vs. 792.9 â€‹± â€‹122.4; O2pulse â€‹= â€‹24.1 â€‹± â€‹0.9 vs. 23.4 â€‹± â€‹0.9 (p<0.05). Results demonstrate that the PMP conferred a significant performance benefit to cyclists completing high intensity cycling exercise.

Signed, Sealed, Delivered: Increasing Patient Notification of Test Results in an Internal Medicine Resident Continuity Clinic.

OBJECTIVES: Informing patients of their test results is an important patient safety issue, yet many physicians perform dismally in this regard. Residents often face additional barriers to communicating test results to patients. We wanted to determine whether streamlining the notification process, communicating expectations, and having residents audit their performance would increase result notification rates. METHODS: We used a quasi-experimental design, and a single-group before-and-after intervention. Our multifold intervention consisted of development and standardization of a notification process in the electronic medical record, an education component, and a self-audit component. During a 15-minute session, we educated residents on the use of the new process. We also restated expectations regarding notifying patients of their results. Residents audited their own charts for a period before the intervention and during a second, postintervention period. An independent review of notification rates took place simultaneously as well as during an additional period several months later. RESULTS: In total, 87 residents were eligible for participation. All 87 completed the project, giving a 100% participation rate. Resident-reported laboratory test notification rates increased from 16% to 91%; other test result rates increased from 33% to 84%. The three independent reviews showed laboratory test notification rates increased from 18.5% to 71.7% to 87.1%, and notification of other test results increased from 23.5% to 66.7% to 91.7%. CONCLUSIONS: Baseline rates of notification for diagnostic tests results were low, but streamlining the notification process, clearly stating expectations for using it, and using resident self-audit can improve notification rates.

Sex Differences and Estrous Cycle Effects of Peripheral Serotonin-Evoked Rodent Pain Behaviors.

Many persistent pain conditions occur predominantly in women making pain a major women's health issue. One theory for the prevalence in females is hormone modulation of pain mechanisms. The peripheral release of the neurotransmitter serotonin (5HT) has been implicated in various sexually dimorphic pain conditions; yet no studies have examined the effect of ovarian hormones on peripheral 5HT-evoked pain behaviors. We hypothesized that peripheral 5HT evokes greater pain behaviors in female rodents during estrus and/or proestrus, stages of the estrous cycle where ovarian hormones are greatly fluctuating. Female Sprague-Dawley rats (250-350 g) from each stage of the estrous cycle, ovariectomized females, and intact males received an intraplantar hindpaw injection of 5HT (2 µg/100 µL) or saline (n = 6 per group) and thermal hyperalgesia, mechanical allodynia, or edema was measured at 0, 10, 20 and 30 min post-injection. A separate group of rats received an ipsilateral injection of the selective 5HT2A antagonist, M100907, 15 min prior to 5HT injection. We report that females in proestrus and estrus exhibited significantly greater and/or longer lasting pain behaviors compared to males, females in diestrus, and ovariectomized females. There were no significant sex differences or estrous cycle effects on 5HT-evoked edema or 5HT content in inflamed hindpaws. Local pretreatment with the 5HT2A receptor antagonist blocked 5HT-evoked thermal hyperalgesia and edema. These data provide evidence of a modulatory role of hormones on peripheral 5HT-evoked pain occurring via the 5HT2A receptor.