Rejected

Experimental studies show that human pain sensitivity varies across the 24-hour day, with the lowest sensitivity usually occurring during the afternoon. Patients suffering from neuropathic pain, or nerve damage, experience an inversion in the daily modulation of pain sensitivity, with the highest sensitivity usually occurring during the early afternoon. Processing of painful stimulation occurs in the dorsal horn (DH), an area of the spinal cord that receives input from peripheral tissues via several types of primary afferent nerve fibers. The DH circuit is composed of different populations of neurons, including excitatory and inhibitory interneurons, and projection neurons, which constitute the majority of the output from the DH to the brain. In this work, we develop a mathematical model of the dorsal horn neural circuit to investigate mechanisms for the daily modulation of pain sensitivity. The model describes average firing rates of excitatory and inhibitory interneuron populations and projection neurons, whose activity is directly correlated with experienced pain. Response in afferent fibers to peripheral stimulation is simulated by a Poisson process generating nerve fiber spike trains at variable firing rates. Model parameters for fiber response to stimulation and the excitability properties of neuronal populations are constrained by experimental results found in the literature, leading to qualitative agreement between modeled responses to pain and experimental observations. We validate our model by reproducing the wind-up of pain response to repeated stimulation. We apply the model to investigate daily modulatory effects on pain inhibition, in which response to painful stimuli is reduced by subsequent non-painful stimuli. Finally, we use the model to propose a mechanism for the observed inversion of the daily rhythmicity of pain sensation under neuropathic pain conditions. Underlying mechanisms for the shift in rhythmicity have not been identified experimentally, but our model results predict that experimentally-observed dysregulation of inhibition within the DH neural circuit may be responsible. The model provides an accessible, biophysical framework that will be valuable for experimental and clinical investigations of diverse physiological processes modulating pain processing in humans.

Patients with acute aneurysmal subarachnoid hemorrhage (aSAH) experience excruciating headache that is difficult to manage in resource-constrained settings. Pregabalin's (β-isobutyl-GABA) analgesic, antiepileptic, and antiemetic properties make it an attractive adjuvant in pain management for these patients. We conducted a double-blind, placebo-controlled, randomized clinical trial on 40 aSAH patients undergoing aneurysmal clipping to assess the effect of perioperative pregabalin in decreasing perioperative headache, anesthetic, and opioid requirement. Patients received either pregabalin (75 mg) or placebo twice daily soon after admission till 24-hour postoperative, in addition to paracetamol 650 mg thrice daily. Headache assessed using a visual analog scale (VAS) at five time points was compared using a mixed effects regression model. Pain assessed by VAS declined significantly more from the baseline in pregabalin recipients compared with placebo at preinduction (-3.6 vs.-1.8; = 0.004), 12-hour (4.3 vs. 2.8; = 0.014), and 24-hour postsurgery (4.7 vs. 2.9; = 0.007), but not at the 6-hour postoperation (4.9 vs. 3.8; = 0.065). Pregabalin recipients required a lower minimum alveolar concentration of sevoflurane to maintain a prespecified bispectral index of 40 and 60 (0.8 vs. 0.9; = 0.014) and required fewer rescue analgesic doses in the 24  hours following surgery (1.8 vs. 3.3; = 0.005). The intraoperative fentanyl requirement was not significantly different between the groups (10 μg/kg vs. 11.4 μg/kg; = 0.065). There was no significant difference in the sedation scores. Pregabalin 75 mg administered twice daily, during the perioperative period, was an effective adjunct in the management of the severe headache experienced by patients with aSAH and decreased the opioid and anesthetic requirement without significantly increasing sedation.

To investigate the efficacy of eltrombopag for the treatment of thrombocytopenia in patients with chronic hepatitis C, a phase II, single-arm, open-label study with a 9-week pre-antiviral phase was conducted, followed by a 48-week antiviral phase and a 24-week follow-up phase. The proportion of patients who achieved a platelet count threshold, the proportion of patients who maintained a platelet count >50,000/µl, sustained virological response (SVR) rates and safety parameters were evaluated. Of the 45 enrolled patients (median age, 59 years; median platelet count, 63,000/µl; 98% with Child-Pugh class A), 43 (96%) achieved the platelet count threshold during the pre-antiviral phase. A total of 13 patients (29%) experienced ≥1 adverse event (AE), of which headache and vomiting were the most common, and 41 patients (mostly receiving eltrombopag 12.5 mg or 25 mg) entered the antiviral phase, of which 36 (88%) maintained the platelet count threshold; no patient platelet count decreased below 25,000/µl. Nine patients (22%) achieved an SVR at the 24-week follow-up. Grade ≥3 AEs occurred in 25 patients (61%). A total of 8 serious AEs occurred in five patients (12%). No mortality, thromboembolic events (TEEs), or cataract progression were reported. Eltrombopag increased the platelet count in chronic hepatitis C virus-infected patients with cirrhosis and thrombocytopenia and enabled them to initiate and complete interferon-based antiviral therapy (NCT01636778; first submitted: July 05, 2012).

Infant colic, or excessive crying in an otherwise healthy infant, is common, although the cause(s) are not known. This study aimed to determine whether parental migraine is associated with infant colic.

Neurovascular compression syndromes (NVCS) could be cured with an intravascular device that releases compression of the root entry zone of cranial nerves by changing the course of offending vessels. The purpose of this study was to report our results of in vitro and in vivo experiments with a novel intra-arterial neurovascular decompressor (IA-NVD) for NVCS.

Low back pain is a common and very prevalent disease and can impose limitations that negatively impact patients. The objective of this study was to verify and compare the association between lumbar superficial temperature and pressure pain tolerance thresholds in individuals with chronic nonspecific low back pain and healthy controls.

The purpose of this study was to provide an updated systematic review and meta-analysis regarding the effectiveness of mobilization with movement (MWM) techniques on range of motion (ROM).

Pain is a unique and subjective experience that has a prominent function in animals' survival. Observation of pain in others leads to alterations in pain sensation and affection, termed "Empathy for pain". The present study aimed to evaluate the effect of empathy on sensory and affective dimensions of pain and its effect on anxiety-like behaviors. In this study, male Wistar rats were used. Two cage mates were selected, one of which underwent administration of a noxious stimuli for 10 days and the other observed the conspecific in pain. Hot plate, tail flick, and conditioned place aversion were used to evaluate sensory and affective dimensions of pain, respectively. Anxiety-like behavior was assayed using elevated plus maze paradigm and time spent in open and close arms and number of entrance into each arm was recorded as the anxiety indicator within a 5-minute framework. Rats observing the cage mate in pain had a lower threshold to noxious stimuli in comparison to controls. They also had an increased aversion from painful stimuli, demonstrating heightened affective response to pain. Anxiety-like behavior was also enhanced in the observers. Results of this study demonstrate that both sensory and affective dimensions of pain are altered following observation of pain in a conspecific. Further studies evaluating the underlying mechanisms are encouraged to elucidate the role of different neurotransmitters in this phenomenon.