Post-herpetic neuralgia (PHN) is a chronic neuropathic pain condition that persists 3 months or more following an outbreak of shingles. Shingles, also known as acute herpes zoster, is associated with the reactivation of the dormant varicella zoster virus in an individual who has experienced chicken pox. PHN is associated with persistent and often refractory neuropathic pain. Patients may experience multiple types of pain including a constant deep, aching, or burning pain; a paroxysmal, lancinating pain; hyperalgesia (painful stimuli are more painful than expected); and allodynia (pain associated with typically non-painful stimuli). The pharmacological treatment of PHN may include a variety of medications including alpha-2 delta ligands (gabapentin and pregabalin), other anticonvulsants (carbamazepine), tricyclic antidepressants (amitriptyline, nortriptyline, doxepin), topical analgesics (5 % lidocaine patch, capsaicin) tramadol, or other opioids. The considerable side effect profiles of the commonly used oral medications often limit their practical use, and a combination of both topical and systemic agents may be required for optimal outcomes. Physicians and other treatment providers must tailor treatment based on the response of individual patients.

Rationale Airway thiol redox disturbances, including depletion of the antioxidant, glutathione (GSH), are differentiating features of severe asthma in children. Objectives Given the role of the transcription factor, Nrf2, in maintaining GSH homeostasis and antioxidant defense, we quantified expression and activity of Nrf2 and its downstream targets in the airways and systemic circulation of asthmatic children. We hypothesized that Nrf2 activation and function would be impaired in severe asthma, resulting in depletion of thiol pools and insufficient GSH synthesis and conjugation. Methods Peripheral blood mononuclear cells (PBMCs) and airway lavage cells were collected from children 6–17 years with severe (n=51) and mild-to-moderate asthma (n=38). The thiols GSH and cysteine (CyS) were quantified and expression and activity of Nrf2 and its downstream targets were assessed. Results Children with severe asthma had greater oxidation and lower concentrations of GSH and Cys in the plasma and airway lavage. Although Nrf2 mRNA and protein increased in severe asthma as a function of increased thiol oxidation, the Nrf2 expressed was highly dysfunctional. Nrf2 activation and downstream targets of Nrf2 binding, including GSH-dependent enzymes, were not different between groups. The duration of asthma was a key factor associated with Nrf2 dysfunction in severe asthma. Conclusions Children with severe asthma have a global disruption of thiol redox signaling and control in both the airways and systemic circulation that is associated with post-translational modification of Nrf2. We conclude that the Nrf2 pathway is disrupted in severe asthma as a function of chronic oxidative stress, which ultimately inhibits GSH synthesis and antioxidant defense.

Background Vitamin D deficiency is common in HIV-infected individuals. In adults, traditional and HIV-related factors play a role in vitamin D status, and deficiency appears to impair immune restoration and exacerbate HIV complications, like cardiovascular disease (CVD). This study sought to determine factors contributing to vitamin D status in HIV-infected youth and investigate the relationship with CVD risk, inflammation, and immune restoration. Methods HIV-infected subjects (1–25 years old) were enrolled prospectively along with healthy controls that were group-matched by age, sex, and race. HIV data were collected for the HIV-infected group, while traditional risk factors, including vitamin D intake, sun exposure, skin pigmentation, physical activity level, and body mass index (BMI) were collected for both groups. Fasting lipids, plasma 25-hydroxyvitamin D (25(OH)D), and inflammation markers were measured. Results 200 HIV-infected subjects and 50 controls were enrolled. HIV group had 53% male, 95% black, and a mean age of 17.2±4.6 years. There was no difference in 25(OH)D between groups; 77% of HIV+ and 74% of controls had 25(OH)D <20 ng/mL. Only Fitzpatrick skin type was independently associated with 25(OH)D. No HIV variables were associated with 25(OH)D, even when HIV sub-populations were examined. Inflammation, CVD risk factors, and immune restoration were not independently associated with 25(OH)D. Conclusions Vitamin D deficiency is common among HIV-infected youth. However, HIV factors, CVD risk, inflammation, and immune restoration do not appear to have the same relationship with vitamin D as has been shown in adults. Supplementation trials are needed to determine if increasing 25(OH)D concentrations could better elucidate these relationships.

Purpose of Review Chronic pain is a widespread public and physical health crisis, as it is one of the most common reasons adults seek medical care and accounts for the largest medical reason for disability in the USA (Glombiewski et al., J Consult Clin Psychol. 86(6):533-545, 2018; Schemer et al., Eur J Pain. 23(3):526-538, 2019). Chronic pain is associated with decreased functional status, opioid dependence and substance abuse disorders, mental health crises, and overall lower perceived quality of life (Korff et al., J Pain. 17(10):1068-1080, 2016). For example, the leading cause of chronic pain and the leading cause of long-term disability is low back pain (LBP) (Bjorck-van Dijken et al. J Rehabil Med. 40:864–9, 2008). Evidence suggests that persistent low back pain (pLBP) is a multidimensional biopsychosocial problem with various contributing factors (Cherkin et al., JAMA. 315(12):1240-1249, 2016). Emotional distress, pain-related fear, and protective movement behaviors are all unhelpful lifestyle factors that previously were more likely to go unaddressed when assessing and treating patient discomfort (Pincus et al., Spine. 38:2118–23, 2013). Those that are not properly assisted with these psychosocial issues are often unlikely to benefit from treatment in the primary care setting and thus are referred to multidisciplinary pain rehabilitation physicians. This itself increases healthcare costs, and treatments can be invasive and have risks of their own. Therefore, less expensive and more accessible management strategies targeting these psychosocial issues should be started to facilitate improvement early. As a biopsychosocial disorder, chronic pain is influenced by a range of factors including lifestyle, mental health status, familial culture, and socioeconomic status. Physicians have moved toward multi-modal pain approaches in order to combat this public health dilemma, ranging from medications with several different mechanisms of action, lifestyle changes, procedural pain control, and psychological interventions (Fashler et al., Pain Res Manag. 2016:5960987, 2016). Part of the rehabilitation process now more and more commonly includes cognitive behavioral and cognitive functional therapy. Cognitive functional therapy (CFT) and cognitive behavioral therapy (CBT) are both multidimensional psychological approaches to combat the mental portion of difficult pain control. While these therapies are quite different in their approach, they lend to the idea that chronic pain can and should be targeted using coping mechanisms, helping patients understand the pathophysiological process of pain, and altering behavior. Recent Findings CFT differs from CBT functionally, as instead of improving managing/coping mechanisms of pain control from a solely mental approach, CFT directly points out maladaptive behaviors and actively challenges the patient to change them in a cognitively integrated, progressive overloading functional manner (Bjorck-van Dijken et al. J Rehabil Med. 40:8...

The authors would like to point out that on the right hand column on page 3, lastparagraph, lines 3-6 in the original version, the sentence has an error. The correct sentence should read: Traditional gabapentin saturates transporters only in a limited part of the small intestine, while enacarbil has the ability to employ high-capacity nutrient transporters along the entirety of the small and large intestine.On page 17 of the orginal version, in the second paragraph, the sentence that states: BThe oral bioavailability of pregabalin is quite high at over 90 % when taken at 900 mg/day but decreases to 27 % when doses exceed 4800 mg/day [35••, 43].^contains a mistake. The word Bpregabalin^should be corrected to Bgabapentin^. The sentence should read: BThe oral bioavailability of gabapentin is quite high at over 90 % when taken at 900 mg/day but decreases to 27 % when doses exceed 4800 mg/day [35••, 43].^

In patients receiving PVB, immediate and long-term analgesia is superior to systemic analgesia while opioid use and typical adverse effects of systemic analgesia such as nausea and vomiting are decreased. The benefits may also include an improved oncological survival with PVB after mastectomy for malignancy. PVB offers clinically significant benefits for perioperative care of patients undergoing breast surgery. The benefits of continuous PVB are most firmly supported for major breast surgery and include both effective short-term pain control and reduction in burden of chronic pain. On the other hand, minor breast surgery should be effectively manageable using multimodal analgesia in the majority of patients, with PVB reserved as analgesic rescue or for patients at high risk of excessive perioperative pain.

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Summary Children with moderate-to-severe asthma have decreased expression of acetaminophen metabolizing genes and glutathione that may account for the previously-reported risk of acetaminophen in this vulnerable population.