Integrated pain care models and the importance of aligning stakeholder values.

Sustained widespread deployment of clinically and cost-effective models of integrated pain care could be bolstered by optimally aligning shared stakeholder values.

Meditation-induced bloodborne factors as an adjuvant treatment to COVID-19 disease.

The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide. Management of the pandemic has relied mainly on SARS-CoV-2 vaccines, while alternative approaches such as meditation, shown to improve immunity, have been largely unexplored. Here, we probe the relationship between meditation and COVID-19 disease and directly test the impact of meditation on the induction of a blood environment that modulates viral infection. We found a significant inverse correlation between length of meditation practice and SARS-CoV-2 infection as well as accelerated resolution of symptomology of those infected. A meditation "dosing" effect was also observed. In cultured human lung cells, blood from experienced meditators induced factors that prevented entry of pseudotyped viruses for SARS-CoV-2 spike protein of both the wild-type Wuhan-1 virus and the Delta variant. We identified and validated SERPINA5, a serine protease inhibitor, as one possible protein factor in the blood of meditators that is necessary and sufficient for limiting pseudovirus entry into cells. In summary, we conclude that meditation can enhance resiliency to viral infection and may serve as a possible adjuvant therapy in the management of the COVID-19 pandemic.

Unsupervised learning for prognostic validity in patients with chronic pain in transdisciplinary pain care.

Chronic pain is not a singular disorder and presents in various forms and phenotypes. Here we show data from a cohort of patients seeking treatment in a transdisciplinary pain clinic. Patients completed a multidimensional patient-reported battery as part of routine initial evaluation at baseline and at each of the four subsequent visits over 1-year follow-up (0, 1, 3, 6, 12 months). The goal of this work was to use unsupervised modeling approach to identify whether patients with chronic pain undergoing transdisciplinary intensive rehabilitation treatment: (1) can be derived based upon self-reported outcome measures at baseline (or before treatment initiation), (2) are clinically validated based on their clinical diagnosis and medication use, and (3) differ in treatment trajectories over 1 year of transdisciplinary treatment. We applied unsupervised clustering on baseline outcomes using nine patient-reported symptoms and examined treatment trajectories. The three-cluster solution was internally validated. Psychiatric diagnosis, chronic back pain-related disability and symptoms severity determined cluster assignment and treatment prognosis. Conversely, clinical pain severity had lesser effect. Furthermore, clusters showed stability over time despite symptoms improvement. The accurate and meaningful subgrouping of the underlying chronic pain phenotypes would greatly enhance treatment and provide personalized and effective pain management.

Cannabidiol as a Treatment for Chronic Pain: A Survey of Patients' Perspectives and Attitudes.

INTRODUCTION: Cannabis products have become easily available and accessible after decriminalization of cannabis for recreational and medicinal use in many states. Cannabidiol (CBD) has been of increasing interest to patients and is being used to self-medicate a variety of ailments. However, very limited information is available to patients and providers to form an educated opinion regarding its indicated use to treat the many conditions this substance has been implied to be helpful for. The aim of this survey was to learn about participants' attitudes and views towards cannabis-based medicine (CBM) with a focus on perception of "CBD" and its potential role for pain management. MATERIALS AND METHODS: We recruited survey participants from seven pain management clinics in Southern California to learn about their knowledge, beliefs, and personal experience with CBD products. After Institutional Review Board (IRB) review, an internet survey platform was utilized to administer the survey online. RESULTS: A total of 253 participants answered the survey. Participants were 45.4 ± 13.8 (Mean ± SD) years of age, the majority identified as white (56.1%), had an annual household income of less than $20,000, and were primarily insured by Medicare (22.5%) or Medicaid (43.9%). Among participants, 62.0% reported trying a CBD product [including products containing delta-9-tetrahydrocannabinol (THC)]. The majority responded that these products have helped their pain (59.0%) and allowed them to reduce their pain medications (67.6%), including opioids (53.7%). They reported believing that CBD was a good treatment option (71.1%), not harmful (74.9%), and not addictive (65.3%). About half of participants (51.9%) report that they would be more comfortable with their physician prescribing CBD products. The overall attitude and experience of participants regarding CBD is reported as positive, while 91.9% of people expressed a desire to learn more about it. SUMMARY: In summary, most participants expressed a positive attitude about CBD products as a treatment option, reported positive outcomes when used for multiple different conditions, and would prefer to obtain information about and prescription for CBD from their physicians.

Post-Traumatic Stress Disorder Symptoms Contribute to Worse Pain and Health Outcomes in Veterans With PTSD Compared to Those Without: A Systematic Review With Meta-Analysis.

INTRODUCTION: Post-traumatic stress disorder (PTSD) and chronic pain are frequently co-morbid conditions in the U.S. veteran population. Although several theories about the cause of increased pain prevalence in individuals with PTSD have been presented, no synthesis of primary data informing the impact of co-morbid PTSD and pain has been completed. The purpose of this study was to systematically review the literature and quantify disability, function, and pain-related beliefs and outcomes in veterans with PTSD compared to veterans without PTSD. MATERIALS AND METHODS: A systematic search of three electronic databases was conducted. Inclusion criteria required pain-related comparison of veterans with PTSD to those without PTSD. Primary outcome measures and standardized mean differences (SMDs) were assessed for pain, function, disability, pain beliefs, and healthcare utilization using a random effects model. RESULTS: 20 original research studies met inclusion criteria and were assessed for quality and outcomes of interest. The majority of studies were cross-sectional. Veterans with PTSD and pain demonstrated higher pain (SMD = 0.58, 95% CI 0.28-0.89), disability (SMD = 0.52, 95%CI 0.33-0.71), depression (SMD = 1.40, 95%CI 1.2-1.6), catastrophizing beliefs (SMD = 0.95, 95% CI 0.69-1.2), sleep disturbance (SMD = 0.80, 95% CI 0.57-1.02), and healthcare utilization; they had lower function (SMD = 0.41, 95% CI 0.25-0.56) and pain self-efficacy (SMD = 0.77, 95% CI 0.55-0.99) compared to veterans without PTSD. CONCLUSION: In veterans with chronic pain, PTSD symptomology has a large effect for many negative health-related outcomes. This review supports the need for clinicians to screen and understand the effects of PTSD symptoms on patients with pain. Clinicians should recognize that veterans with PTSD and pain likely have elevated pain catastrophizing beliefs and decreased self-efficacy that should be targeted for intervention.

Objective Epidural Space Identification Using Continuous Real-Time Pressure Sensing Technology: A Randomized Controlled Comparison With Fluoroscopy and Traditional Loss of Resistance.

BACKGROUND: Performance of epidural anesthesia and analgesia depends on successful identification of the epidural space (ES). While multiple investigations have described objective and alternative methodologies to identify the ES, traditional loss of resistance (LOR) and fluoroscopy (FC) are currently standard of care in labor and delivery (L&D) and chronic pain (CP) management, respectively. While FC is associated with high success, it exposes patients to radiation and requires appropriate radiological equipment. LOR is simple but subjective and consequently associated with higher failure rates. The purpose of this investigation was to compare continuous, quantitative, real-time, needle-tip pressure sensing using a novel computer-controlled ES identification technology to FC and LOR for lumbar ES identification. METHODS: A total of 400 patients were enrolled in this prospective randomized controlled noninferiority trial. In the CP management arm, 240 patients scheduled to receive a lumbar epidural steroid injection had their ES identified either with FC or with needle-tip pressure measurement. In the L&D arm, 160 female patients undergoing lumbar epidural catheter placements were randomized to either LOR or needle-tip pressure measurement. Blinded observers determined successful ES identification in both arms. A modified intention-to-treat protocol was implemented, with patients not having the procedure for reasons preceding the intervention excluded. Noninferiority of needle-tip pressure measurement regarding the incidence of successful ES identification was claimed when the lower limit of the 97.27% confidence interval (CI) for the odds ratio (OR) was above 0.50 (50% less likely to identify the ES) and P value for noninferioirty <.023. RESULTS: Demographics were similar between procedure groups, with a mild imbalance in relation to gender when evaluated through a standardized difference. Noninferiority of needle-tip pressure measurement was demonstrated in relation to FC where pain management patients presented a 100% success rate of ES identification with both methodologies (OR, 1.1; 97.27% CI, 0.52-8.74; P = .021 for noninferiority), and L&D patients experienced a noninferior success rate with the novel technology (97.1% vs 91%; OR, 3.3; 97.27% CI, 0.62-21.54; P = .019) using a a priori noninferiority delta of 0.50. CONCLUSIONS: Objective lumbar ES identification using continuous, quantitative, real-time, needle-tip pressure measurement with the CompuFlo Epidural Computer Controlled Anesthesia System resulted in noninferior success rates when compared to FC and LOR for CP management and L&D, respectively. Benefits of this novel technology may include nonexposure of patients to radiation and contrast medium and consequently reduced health care costs.

Vitamin B12 as a Treatment for Pain.

BACKGROUND: First isolated as cyanocobalamin in 1948, vitamin B12 has been explored for pain treatment almost since its discovery. With the advent of the opioid epidemic, safer treatments for pain are needed. OBJECTIVES: Our objective was to compile the latest information on potential mechanisms from animal studies and clinical trial data on vitamin B12 for the treatment of pain conditions. STUDY DESIGN: We conducted a narrative review. METHODS: PubMed was searched using the terms "methylcobalamin pain", "hydroxycobalamin pain", "cyanocobalamin pain", and "vitamin B12 pain." Animal studies that identified mechanisms of action for the effects of pain were collected. Clinical trials utilizing larger, pharmaceutical doses of vitamin B12 (> 100 µg/dose) in pain treatment were identified and reviewed. RESULTS: Animal studies support multiple beneficial effects of vitamin B12 including the regeneration of nerves and the inhibition of cyclooxygenase enzymes and other pain-signaling pathways. In addition, animal studies have demonstrated synergistic benefits of vitamin B12 combined with other pain medications, including nonsteroidal anti-inflammatory drugs and opiates. Clinical trials provide evidence for the effectiveness of vitamin B12 for the treatment of low back pain and neuralgia, although data is still fairly limited and optimal treatment regimens have not been identified. LIMITATIONS: More large, double-blind placebo-controlled trials are needed to fully establish efficacy and best dosing parameters. CONCLUSION: Vitamin B12 may prove to be an adjunctive or integrative treatment for pain conditions. While more research is needed, considering the low incidence of side effects and overall safety, B12 may be an additional tool to consider for pain treatment. KEY WORDS: Vitamin B12, cyanocobalamin, methylcobalamin, hydroxycobalamin, pain, chronic pain, neuropathy, low back pain.

Relations of combat stress and posttraumatic stress disorder to 24-h plasma and cerebrospinal fluid interleukin-6 levels and circadian rhythmicity.

BACKGROUND: Acute and chronic stress can lead to a dysregulation of the immune response. Growing evidence suggests peripheral immune dysregulation and low-grade systemic inflammation in posttraumatic stress disorder (PTSD), with numerous reports of elevated plasma interleukin-6 (IL-6) levels. However, only a few studies have assessed IL-6 levels in the cerebrospinal fluid (CSF). Most of those have used single time-point measurements, and thus cannot take circadian level variability and CSF-plasma IL-6 correlations into account. METHODS: This study used time-matched, sequential 24-h plasma and CSF measurements to investigate the effects of combat stress and PTSD on physiologic levels and biorhythmicity of IL-6 in 35 male study volunteers, divided in 3 groups: (PTSD = 12, combat controls, CC = 12, and non-deployed healthy controls, HC = 11). RESULTS: Our findings show no differences in diurnal mean concentrations of plasma and CSF IL-6 across the three comparison groups. However, a significantly blunted circadian rhythm of plasma IL-6 across 24 h was observed in all combat-zone deployed participants, with or without PTSD, in comparison to HC. CSF IL-6 rhythmicity was unaffected by combat deployment or PTSD. CONCLUSIONS: Although no significant group differences in mean IL-6 concentration in either CSF or plasma over a 24-h timeframe was observed, we provide first evidence for a disrupted peripheral IL-6 circadian rhythm as a sequel of combat deployment, with this disruption occurring in both PTSD and CC groups. The plasma IL-6 circadian blunting remains to be replicated and its cause elucidated in future research.

Heart rate analysis by sparse representation for acute pain detection.

Objective pain assessment methods pose an advantage over the currently used subjective pain rating tools. Advanced signal processing methodologies, including the wavelet transform (WT) and the orthogonal matching pursuit algorithm (OMP), were developed in the past two decades. The aim of this study was to apply and compare these time-specific methods to heart rate samples of healthy subjects for acute pain detection. Fifteen adult volunteers participated in a study conducted in the pain clinic at a single center. Each subject's heart rate was sampled for 5-min baseline, followed by a cold pressor test (CPT). Analysis was done by the WT and the OMP algorithm with a Fourier/Wavelet dictionary separately. Data from 11 subjects were analyzed. Compared to baseline, The WT analysis showed a significant coefficients' density increase during the pain incline period (p < 0.01) and the entire CPT (p < 0.01), with significantly higher coefficient amplitudes. The OMP analysis showed a significant wavelet coefficients' density increase during pain incline and decline periods (p < 0.01, p < 0.05) and the entire CPT (p < 0.001), with suggestive higher amplitudes. Comparison of both methods showed that during the baseline there was a significant reduction in wavelet coefficient density using the OMP algorithm (p < 0.001). Analysis by the two-way ANOVA with repeated measures showed a significant proportional increase in wavelet coefficients during the incline period and the entire CPT using the OMP algorithm (p < 0.01). Both methods provided accurate and non-delayed detection of pain events. Statistical analysis proved the OMP to be by far more specific allowing the Fourier coefficients to represent the signal's basic harmonics and the wavelet coefficients to focus on the time-specific painful event. This is an initial study using OMP for pain detection; further studies need to prove the efficiency of this system in different settings.

A randomized, double-blind, crossover study to evaluate the depth response relationship of intradermal capsaicin-induced pain and hyperalgesia in healthy adult volunteers.

OBJECTIVE: The purpose of this study was to evaluate pain and hyperalgesia in response to different depths of intradermal (ID) capsaicin injections in healthy volunteers. DESIGN: Double-blind, cross-over study. SETTING: Clinical Research Laboratory. SUBJECTS: Fifteen healthy male subjects received ID capsaicin injections into the volar aspect of each forearm at depths of 1 mm, 3 mm, 5 mm, and 7 mm. After injection, spontaneous pain, elicited pain, flare response, heat thresholds, and area of hyperalgesia were measured at various time points. OUTCOMES MEASURE: Spontaneous pain, elicited pain (pinprick, stroking, and hot pain), hyperalgesia area, and allodynia area. RESULTS: No significant difference was found between any depths in spontaneous pain, elicited pain (pinprick, stroking, hot pain), hyperalgesia area, or allodynia area. A significant difference was found in the change in heat threshold between 5 mm and 1 mm, 7 mm and 1 mm, 5 mm and 3 mm, 7 mm and 3 mm depths. A significant difference was found in flare area between 5 mm and 3 mm depths. A significant difference was found in systolic blood pressure area under the curve (AUC) between 7 mm and 1 mm depths, and for both systolic and diastolic pressures for 5 mm and 1 mm depths, and 5 mm and 3 mm depths. A significant difference was found in pulse AUC between 5 mm and 1 mm depths and 5 mm and 3 mm depths. CONCLUSIONS: Injection of capsaicin at different depths in the skin had different effects on heart rate and blood pressure but no effect on pain. These results may have implications on the pharmacology and analgesic predictive value of the model of ID capsaicin.

Evidence for acute central sensitization to prolonged experimental pain in posttraumatic stress disorder.

BACKGROUND: Post-traumatic stress disorder (PTSD) and pain have a well-documented high comorbidity; however, the underlying mechanisms of this comorbidity are currently poorly understood. The aim of this psychophysical study was to investigate the behavioral response to a prolonged suprathreshold pain stimulus in subjects with combat-related PTSD and combat controls (CC) for clinical evidence of central sensitization. METHODS: Ten male subjects with current PTSD related to combat and 11 CC male subjects underwent baseline quantitative sensory testing (QST), temporal pain summation, and psychological profiling followed by an intramuscular injection of capsaicin into the quadriceps muscle. RESULTS: There was no significant between-group difference for the initial maximal pain response or an initial pain reduction for the first 15 minutes postinjection on QST or pain ratings. However, we observed significantly higher scores in the PTSD group for the second 15 minutes postinjection on both pain intensity and pain unpleasantness ratings. Assessment of temporal summation to repetitive pressure stimuli showed significantly higher subjective pain in the PTSD group. CONCLUSION: These findings are consistent with a significantly higher degree of acute central sensitization in individuals with PTSD. Increased acute central sensitization may underlie increased vulnerability for developing pain-related conditions following combat trauma.

Circadian rhythmicity, variability and correlation of interleukin-6 levels in plasma and cerebrospinal fluid of healthy men.

BACKGROUND: Interleukin-6 (IL-6) is a cytokine with pleiotropic actions in both the periphery of the body and the central nervous system (CNS). Altered IL-6 secretion has been associated with inflammatory dysregulation and several adverse health consequences. However, little is known about the physiological circadian characteristics and dynamic inter-correlation between circulating and CNS IL-6 levels in humans, or their significance. METHODS: Simultaneous assessment of plasma and cerebrospinal fluid (CSF) IL-6 levels was performed hourly in 11 healthy male volunteers over 24h, to characterize physiological IL-6 secretion levels in both compartments. RESULTS: IL-6 levels showed considerable within- and between-subject variability in both plasma and CSF, with plasma/CSF ratios revealing consistently higher levels in the CSF. Both CSF and plasma IL-6 levels showed a distinctive circadian variation, with CSF IL-6 levels exhibiting a main 24h, and plasma a biphasic 12h, circadian component. Plasma peaks were roughly at 4 p.m. and 4 a.m., while the CSF peak was at around 7 p.m. There was no correlation between coincident CSF and plasma IL-6 values, but evidence for significant correlations at a negative 7-8h time lag. CONCLUSIONS: This study provides evidence in humans for a circadian IL-6 rhythm in CSF and confirms prior observations reporting a plasma biphasic circadian pattern. Our results indicate differential IL-6 regulation across the two compartments and are consistent with local production of IL-6 in the CNS. Possible physiological significance is discussed and implications for further research are highlighted.

Specific pain complaints in Iraq and Afghanistan veterans screening positive for post-traumatic stress disorder.

BACKGROUND: Post-traumatic stress disorder (PTSD) and pain are highly comorbid. OBJECTIVE: The purpose of this study was to examine the association of PTSD with specific pain complaints in veterans of Operations Enduring and Iraqi Freedom (OEF/OIF). METHOD: A total of 381 primarily male (88.5%) veterans with a mean age of 30 years completed a battery of self-report questionnaires. A positive PTSD screen was defined as a score of ≥40 on the Davidson Trauma Scale. Logistic regression was used to examine the association of positive PTSD screen with specific pain complaints. RESULTS: There were no significant demographic or physical and mental health differences between veterans who screened positive for PTSD only and those with PTSD and at least one pain complaint, although differences on rates of combat injury and depression approached significance. Veterans who screened positive for PTSD were 2 to 3 times more likely to report abdominal pain, muscle aches or cramps, and joint aches, even after controlling for age, gender, combat injury, and depression. CONCLUSIONS: Similar to findings in other populations, there is a relationship between PTSD and pain complaints in OEF/OIF veterans. Future research should examine the mechanisms that link PTSD with specific pain complaints, especially abdominal pain.

Treating intractable phantom limb pain with ambulatory continuous peripheral nerve blocks: a pilot study.

BACKGROUND: There is currently no reliable treatment for phantom limb pain (PLP). Chronic PLP and associated cortical abnormalities may be maintained from abnormal peripheral input, raising the possibility that a continuous peripheral nerve block (CPNB) of extended duration may permanently reorganize cortical pain mapping, thus providing lasting relief. METHODS: Three men with below-the-knee (2) or -elbow (1) amputations and intractable PLP received femoral/sciatic or infraclavicular perineural catheter(s), respectively. Subjects were randomized in a double-masked fashion to receive perineural ropivacaine (0.5%) or normal saline for over 6 days as outpatients using portable electronic infusion pumps. Four months later, subjects returned for repeated perineural catheter insertion and received an ambulatory infusion with the alternate solution ("crossover"). Subjects were followed for up to 1 year. RESULTS: By chance, all three subjects received saline during their initial infusion and reported little change in their PLP. One subject did not receive crossover treatment, but the remaining two subjects reported complete resolution of their PLP during and immediately following treatment with ropivacaine. One subject experienced no PLP recurrence through the 52-week follow-up period and the other reported mild PLP occurring once each week of just a small fraction of his original pain (pretreatment: continuous PLP rated 10/10; posttreatment: no PLP at baseline with average of one PLP episode each week rated 2/10) for 12 weeks (lost to follow-up thereafter). CONCLUSIONS: A prolonged ambulatory CPNB may be a reliable treatment for intractable PLP. The results of this pilot study suggest that a large, randomized clinical trial is warranted.

Sensory small fiber function differentially assessed with diode laser (DL) quantitative sensory testing (QST) in painful neuropathy (PN).

Sensory function of small peripheral nerve fiber was assessed by means of quantitative sensory testing (QST) during which sensory stimulation was provided using diode laser (DL) in patients suffering from painful neuropathy (PN) and compared with symptom-free healthy controls (HC). Based on previous research work using DL stimulation, parameters that demonstrated safe and specific activation of A-delta, which were distinct from stimulation parameters for the activation of C-fibers, were utilized in this study. Results of this study demonstrated that this differential activation pointed to the impaired function of A-delta fibers while C-fiber function was unaffected. Stimulation of HC reproduced previously published results, and stimulation during this study was safe also without any dermal effect in patients with PN and in HC. Parameters used in this study were demonstrated in previous preclinical rodent study identical differential effect on activation of A-delta and C-fibers, and as such, DL is an ideal tool for translational pain research where specific activation of A-delta or C-fibers, or both, is required.

Cortisol response to experimental pain in patients with chronic low back pain and patients with major depression.

OBJECTIVE: Chronic pain and major depression have been associated with alterations of the hypothalamus-pituitary-adrenal axis (HPA) activity. Previous studies suggested that HPA activity is diminished in chronic pain but increased in depression. However, little is known about the effects of experimentally induced acute pain on cortisol secretion in patients with chronic pain and depression. METHODS: On three different occasions (day 1, day 8, day 90), we repeatedly examined 20 patients with chronic low back pain without depression, 22 patients with major depression without pain, and 33 healthy subjects using heat stimuli. Pain intensity was rated by participants using a visual analog scale. Salivary cortisol was assessed prior to 10 blocks of repeated painful heat stimuli, and 45 and 60 minutes afterwards. RESULTS: In repeated measures analyses of covariance adjusting for age, sex, and time of examination, we found a significant effect of group (P < 0.01) and post-hoc tests confirmed that patients with chronic pain had lower cortisol area-under-the-curve values compared with healthy controls and depressed patients at all time points (all P values <0.01). However, cortisol secretion in depressed patients did not differ from controls. CONCLUSIONS: Across groups, experimental heat pain stimuli did not elicit a significant cortisol response. Chronic pain appears to be associated with low cortisol secretion. The mechanisms linking chronic pain with low cortisol deserve further study.

Diminished vagal activity and blunted diurnal variation of heart rate dynamics in posttraumatic stress disorder.

Affected autonomic heart regulation is implicated in the pathophysiology of cardiovascular diseases and is associated with posttraumatic stress disorder (PTSD). However, although sympathetic hyperactivation has been repeatedly shown in PTSD, research has neglected parasympathetic function. The objective of this study is the long-term assessment of heart rate (HR) dynamics and its diurnal changes as an index of autonomic imbalance in PTSD. Since tonic parasympathetic activity underlies long-range correlation of heartbeat interval fluctuations in the healthy state, we included nonlinear (unifractal) analysis as an important and sensitive readout to assess functional alterations. We conducted electrocardiogram recordings over a 24-h period in 15 deployed male subjects with moderate to high levels of combat exposure (PTSD: n = 7; combat controls: n = 8) in the supine position. HR dynamics were assessed in two 5-h sub-epochs in the time and frequency domains, and by nonlinear analysis based on detrended fluctuation analysis. Psychiatric symptoms were assessed using structured interviews, including the Clinician Administered PTSD Scale. Subjects with PTSD showed significantly higher baseline HR, higher LF/HF ratio in the frequency domain, blunted differences between day and night-time measures, as well as a higher scaling coefficient αfast during the day, indicating diminished tonic parasympathetic activity. Diminished diurnal differences and blunted tonic parasympathetic activity altering HR dynamics suggest central neuroautonomic dysregulation that could represent a possible link to increased cardiovascular disease in PTSD.

Gabapentin for once-daily treatment of post-herpetic neuralgia: a review.

Post-herpetic neuralgia is a neuropathic pain syndrome resulting from an insult to the peripheral and central nervous systems caused by the varicella zoster virus. Spontaneous pain may result in the persistent sensation of burning, tingling, or aching and may be associated with thermally or mechanically provoked pain, resulting in hyperalgesia or allodynia. The majority of cases occur in patients over the age of 50 years. Gabapentin is a structural analog of gamma aminobutyric acid that binds to the α(2)-δ site of voltage-dependent calcium channels and modulates the influx of calcium, with a resulting reduction in excitatory neurotransmitter release. Gabapentin is effective in reducing neuropathic pain due to post-herpetic neuralgia when given at least three times per day, due to its short half-life, resulting in demonstrable fluctuations in plasma levels. Gabapentin has dose-limiting side effects that prevent some patients from achieving therapeutic plasma levels, such as somnolence (27.4%), dizziness (23.9%), and ataxia (7.1%). Gralise™ is a once-daily extended-release formulation of gabapentin that has been developed using AcuForm™ technology. AcuForm is a polymer-based drug delivery system that retains the tablet in the stomach and upper gastrointestinal tract for a sustained period of time. Once-daily dosing has been shown to provide comparable drug exposure with an identical daily dose of the immediate-release formulation when administered three times daily. Participants given Gralise 1800 mg daily had a statistically significant reduction in average daily pain intensity scores compared with placebo, reduced sleep interference due to pain, and a greater percent of participants reporting being much or very much improved on the patient global impression of change. An analysis comparing the efficacy and safety profiles in the aging population (≥65 years) with those younger than 65 years showed that Gralise is effective and well tolerated in both age groups.

Health-related quality of life 'well-being' in HIV distal neuropathic pain is more strongly associated with depression severity than with pain intensity.

BACKGROUND: Despite modern antiretroviral treatment, HIV-associated distal neuropathic pain (DNP) remains one of the most prevalent and debilitating complications of HIV disease. Neuropathic pain is often accompanied by depressed mood, and both pain and depression have been associated with decreased health-related quality of life (HRQOL) well-being. The relative contribution of depression and pain to worse life quality has not been addressed, however, even though a better understanding might sharpen intervention strategies. METHODS: We used the Medical Outcomes Study HIV (MOS-HIV) Health Survey and the Beck depression inventory-II and linear regression models to investigate HRQOL well-being in HIV-infected patients with DNP (n = 397) participating in an observational cohort study at six U.S. sites (CNS HIV Antiretroviral Treatment Effects Research Study, CHARTER). RESULTS: For this sample of patients with HIV DNP, severity of depressed mood was more highly correlated with HRQOL well-being than was pain intensity. CONCLUSIONS: These results suggest that interventions to improve HRQOL well-being in individuals with HIV-associated DNP may need to address not only pain intensity but mood state as well.

Pain and post traumatic stress disorder - review of clinical and experimental evidence.

Pain and Post Traumatic Stress Disorder (PTSD) are highly comorbid conditions. Patients with chronic pain have higher rates of PTSD. Likewise, patients with PTSD are often diagnosed with numerous chronic pain conditions. Despite the high pain-PTSD comorbidity, the neurobehavioral mechanisms underlying this phenomenon are incompletely understood and only recently researchers have started investigating it using experimental models. In this article, we systematically review the substantial clinical evidence on the co-occurrence of pain and PTSD, and the limited experimental evidence of pain processing in this disorder. We provide a detailed overview of the psychophysical and brain imaging experiments that compared somatosensory and pain processing in PTSD and non-PTSD populations. Based on the presented evidence, an extensive body of literature substantiates the clinical coexistence of pain and PTSD in patients but the limited experimental data show inconsistent results highlighting the need for well-controlled future studies. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.