Peripheral Neuropathic Pain.

OBJECTIVE: This article synthesizes current knowledge on neuropathic pain, with a brief review of mechanisms, diagnostic approaches, and treatment strategies to help neurologists provide effective and individualized care for patients with this complex condition. LATEST DEVELOPMENTS: The most promising developments in peripheral neuropathic pain are related to the molecular biology of the peripheral nervous system. Systematic molecular and genetic analyses of peripheral nerve terminals and dorsal root ganglia have advanced our understanding of the genetics of function and disease of peripheral nerves, as well as their physiology and clinical manifestations. ESSENTIAL POINTS: Peripheral neuropathic pain, similar to central neuropathic pain, is primarily influenced by the biology and pathophysiology of the underlying structures, peripheral sensory nerves, and their central pathways. The clinical course is widely variable in sensory symptoms and intensities, natural history, and response to treatments.

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.

Beyond numbers: integrating qualitative analysis into quantitative sensory testing for neuropathic pain.

This article investigates the benefits of adopting qualitative and quantitative sensory testing (QQST) in sensory assessment, with a focus on understanding neuropathic pain. The innovative QQST method combines participant qualitative experiences with quantitative psychophysical measurements, offering a more varied interpretation of sensory abnormalities and normal sensory function. This article also explores the steps for the optimization of the method by identifying qualitative signs of sensory abnormalities and standardizing data collection. By leveraging the inherent subjectivity in the test design and participant responses, the QQST method contributes to a more holistic exploration of both normal and abnormal sensory experiences. This article positions the QQST approach as a foundational element within the Sensory Evaluation Network, uniting international experts to harmonize qualitative and quantitative sensory evaluation methods.

Pilot RCT comparing low-dose naltrexone, gabapentin and placebo to reduce pain among people with HIV with alcohol problems.

BACKGROUND: To estimate the effects on pain of two medications (low-dose naltrexone and gabapentin) compared to placebo among people with HIV (PWH) with heavy alcohol use and chronic pain. METHODS: We conducted a pilot, randomized, double-blinded, 3-arm study of PWH with chronic pain and past-year heavy alcohol use in 2021. Participants were recruited in St. Petersburg, Russia, and randomized to receive daily low-dose naltrexone (4.5mg), gabapentin (up to 1800mg), or placebo. The two primary outcomes were change in self-reported pain severity and pain interference measured with the Brief Pain Inventory from baseline to 8 weeks. RESULTS: Participants (N = 45, 15 in each arm) had the following baseline characteristics: 64% male; age 41 years (SD±7); mean 2 (SD±4) heavy drinking days in the past month and mean pain severity and interference were 3.2 (SD±1) and 3.0 (SD±2), respectively. Pain severity decreased for all three arms. Mean differences in change in pain severity for gabapentin vs. placebo, and naltrexone vs. placebo were -0.27 (95% confidence interval [CI] -1.76, 1.23; p = 0.73) and 0.88 (95% CI -0.7, 2.46; p = 0.55), respectively. Pain interference decreased for all three arms. Mean differences in change in pain interference for gabapentin vs. placebo, and naltrexone vs. placebo was 0.16 (95% CI -1.38, 1.71; p = 0.83) and 0.40 (95% CI -1.18, 1.99; p = 0.83), respectively. CONCLUSION: Neither gabapentin nor low-dose naltrexone appeared to improve pain more than placebo among PWH with chronic pain and past-year heavy alcohol use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT4052139).

Psychometric properties of the Persian version of the neuropathic pain questionnaire.

PURPOSE: In this study, we aimed to translate, cross-culturally adapt, and validate the Persian version of the Neuropathic Pain Questionnaire (NPQ-P). METHODS: We translated the NPQ to the Persian language based on the recommended guidelines. Measurement properties (internal consistency (Cronbach's alpha), test-retest reliability (intraclass correlation coefficient), construct validity (compared to DN4 questionnaire), and discriminant ability (Receiver operating curve analysis)) of the NPQ-P were evaluated. A total of 101 patients were enrolled in the study. RESULTS: No modification was needed in the translation and cultural adaptation process. High Cronbach's alpha (0.81) and ICC (0.94) supported good reliability of the NPQ-P. The correlation coefficient between the NPQ-P and DN-4 questionnaires was 0.42, indicated moderate construct validity of the NPQ-P. The NPQ-P demonstrated acceptable discriminant ability (AUC: 0.76 (95% CI: 0.66-0.84)). A total score of -0.3 indicated the highest Youden index with a corresponding sensitivity of 0.84 and specificity of 0.64 for the NPQ-P. CONCLUSION: The NPQ was successfully translated to the Persian language and indicated acceptable reliability, diagnostic accuracy, and discriminant ability. The NPQ-P can be used in a clinical setting adjunct to physical examinations and electrodiagnostic tests for a quick screening to distinguish between patients with neuropathic and non-neuropathic pain.IMPLICATIONS FOR REHABILITATIONNeuropathic Pain Questionnaire (NPQ) can be used for a quick screening to discriminate between patients with neuropathic and nociceptive pain.Persian version of the NPQ (NPQ-P) is a reliable and accurate tool with acceptable discriminant ability.The NPQ-P should be used in clinical setting adjunct to physical examinations and electrodiagnostic tests.

Classification of Qualitative Fieldnotes Collected During Quantitative Sensory Testing: A Step Towards the Development of a New Mixed Methods Approach in Pain Research.

PURPOSE: Quantitative sensory testing (QST) is a standardized method to assess somatosensory function. The collection of qualitative information, during the QST procedure, could be an interesting way to facilitate the characterization of altered sensory perception and the identification of different pain phenotypes. The aims of this study were 1) to classify qualitative fieldnotes of sensory abnormalities collected during an independent QST study, and 2) to generate a qualitative interview guide that could be included in the traditional QST procedure as a step towards the implementation of a mixed methods approach. PATIENTS AND METHODS: QST data were collected from 48 chronic neuropathic pain patients treated with spinal cord stimulation (SCS). Three body areas, with or without SCS, were tested: the painful limb targeted by SCS, the contralateral area, and the ipsilateral upper limb. After each trial of each QST modality, patients were encouraged to report any sensory abnormalities they could identify with a pain quality scale or using their own words. RESULTS: Qualitative self-reported sensory abnormalities were dichotomized into two groups: altered sensory intensities and altered sensory perceptions. Altered sensory intensities were classified as sensory loss or sensory gain subgroups. Altered sensory perceptions were classified as paresthesia and dysesthesia subgroups Overall, 630 qualitative fieldnotes of altered sensations were collected: 385 on the painful limb, 173 at the contralateral area, and 72 at the ipsilateral upper limb. Based on these qualitative data, we propose a standardized method to collect qualitative data involving 9 open- and close-ended questions and 21 codes. CONCLUSION: Our findings have highlighted the value of qualitative sensory evaluation during QST and constitute an important milestone in the development of a mixed methods protocol in phenotyping research.

Evaluation of the Use of Colors and Drawings for Pain Communication for Hmong Patients.

AIMS: The aim of the present study was to explore: (1) the feasibility of using color and pain drawing to describe pain; (2) the cultural appropriateness of pain body diagram (PBD); and (3) the cultural meaning of colors used in pain expression within one cultural group-the Hmong residing in the United States. DESIGN: A qualitative-descriptive study. METHODS: Data were collected sequentially in two phases with different Hmong participants from a Midwestern city using (1) focus groups to determine colors used for pain intensity and qualities along with preferences for drawing versus using the PBD; and (2) individual interviews to determine pain-related meanings of colors and cultural appropriateness of PBDs. Interviews were recorded, transcribed, and analyzed using summative and directed content analyses. RESULTS: Of 67 participants, 73% were female, the average age was 53.7±14.9 years, and 67% received Medicaid. In Phase I, most participants were unable to draw their pain on a blank page and preferred using a PBD. Most could select colors for pain intensity levels, with white and red indicating no pain and severe pain, respectively. In Phase II, white, red, and black had cultural meanings related to pain while colors such as yellow, orange, and blue had personal meanings. All participants perceived the PBD to be culturally appropriate. CONCLUSIONS: The study's findings have implications for how to use colors in pain communication and confirm that PBDs can be used with Hmong patients.

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.

Comparison of Four Pain Scales Among Hmong Patients with Limited English Proficiency.

BACKGROUND: Little is known about the relevance of existing pain scales for patients with limited English proficiency (LEP). AIMS: To determine the ranking and perceptions of four pain intensity scales in LEP Hmong. DESIGN: A sequential mixed-method study. SETTINGS: A Midwestern city, USA. PARTICIPANTS/SUBJECTS: Eight-four Hmong aged 19 to 80 years old. METHODS: Participants ranked four pain intensity scales-the Red Gradation Scale, the Black Gradation Scale, the Wong-Baker Faces Pain Rating Scale, and the Faces Pain Scale - Revised- using Likert responses of 1 (most) to 4 (least) on the following factors: the extent to which they liked the scale, perceived it to be accurate, and preferred to use it in clinical settings. A follow-up interview asked participants' scale selection decisions. Spearman correlations and ordered logistic regression assessed the scale rankings. Thematic analysis was used to analyze the qualitative data. RESULTS: Participants ranked the Wong-Baker Faces Pain Rating Scale as the most liked (3.22 ± 0.95, 50.6%), the most accurate (3.13 ± 0.93, 44.6%), and the most preferred (3.14 ± 1.03, 49.4%). Older Age predicted the selection of this scale. Six themes influenced participants' ranking decisions: the visual clarity of the scale, their experience or familiarity with the scale, the cultural connotations of pain, the type of emotions provoked by scale, the alignment of pain expression reflected in the scale, and the literacy concerns that the scale addressed. CONCLUSIONS: The Wong-Baker Faces could be appropriate for older Hmong. Further validity and reliability studies are needed for the Wong-Baker Faces.

"There Are so Many Nuances . . . ": Health Care Providers' Perspectives of Pain Communication With Hmong Patients in Primary Care Settings.

INTRODUCTION: While researchers have studied Hmong patients with limited English proficiency in pain communication, no research has examined primary care providers' (PCPs') interpretation of Hmong pain communication. This study examines PCPs' pain communication experience with Hmong patients. METHOD: A qualitative content analysis was conducted with PCPs. Interviews were audio recorded, transcribed, and analyzed using conventional content analysis. RESULTS: Fifteen PCPs-including seven physicians, one osteopathic physician, four nurse practitioners, and three physician assistants-participated. PCPs' interpretations of pain communication with Hmong patients were characterized by three themes: (a) the providers experienced pain communication problems related to language, (b) the providers perceived the Hmong to have different beliefs about pain, and (c) the providers used different strategies to improve communication. DISCUSSION: The findings suggest that challenges are present in achieving effective pain communication between Hmong patients and their PCPs. Ineffective pain communication hinders the delivery of culturally congruent health care for Hmong patients.

Colored Pain Drawing as a Clinical Tool in Differentiating Neuropathic Pain from Non-Neuropathic Pain.

OBJECTIVES: This is a prospective, blinded, case-control study of patients with chronic pain using body diagrams and colored markers to show the distribution and quality of pain and sensory symptoms (aching, burning, tingling, numbness, and sensitivity to touch) experienced in affected body parts. METHODS: Two pain physicians, blinded to patients' clinical diagnoses, independently reviewed and classified each colored pain drawing (CPD) for presence of neuropathic pain (NeuP) vs. non-neuropathic pain (NoP). A clinical diagnosis (gold standard) of NeuP was made in 151 of 213 (70.9%) enrolled patients. RESULTS: CPD assessment at "first glance" by both examiners resulted in correctly categorizing 137 (64.3% by examiner 1) and 156 (73.2% by examiner 2) CPDs. Next, classification of CPDs by both physicians, using predefined criteria of spatial distribution and quality of pain-sensory symptoms, improved concordance to 212 of 213 CPDs (Kappa = 0.99). The diagnostic ability to correctly identify NeuP and NoP by both examiners increased to 171 (80.2%) CPDs, with 80.1% sensitivity and 80.6% specificity (Kappa = 0.56 [95% confidence interval: 0.44-0.68]). The severity scores for pain and sensory symptoms (burning, tingling, numbness, and sensitivity to touch) on the Neuropathic Pain Questionnaire were significantly elevated in NeuP vs. NoP (P < 0.001). CONCLUSIONS: This study demonstrates good performance characteristics of CPDs in identifying patients with NeuP through the use of a simple and easy-to-apply classification scheme. We suggest use of CPDs as a bedside screening tool and as a method for phenotypic profiling of patients by the quality and distribution of pain and sensory symptoms.

"It Hurts as If ": Pain-Associated Language, Visual Characterization, and Storytelling in Hmong Adults.

OBJECTIVE: Pain is challenging to diagnose and manage in primary care, especially when patients have limited English proficiency (LEP). Little is known about whether LEP patients can provide pain information that is consistent with the process and the content that providers expect in a clinical interaction. We explore how LEP Hmong patients communicate their pain to providers in primary care settings. METHODS: A qualitative study with 67 Hmong participants (63% female and x̄ age = 53.7 years) were recruited from a Midwestern state. Semistructured interviews on pain communication were conducted, audio-recorded, transcribed, and analyzed using directed content analysis. RESULTS: The Hmong participants described pain using stories that generally had the same dimensions of information that providers require for pain assessment. These included references to time, causality, associated symptoms or related experiences, intensity, and consequences of pain. However, the participants expressed some pain dimensions in language that was not shared by providers: visual metaphors that were generally in reference to pain quality and fewer words for pain location, intensity, and some qualities. Participants used two strategies to decide whether they should tell their pain story: assessing the provider and determining whether their story was appreciated. The perception that providers underappreciated their stories resulted in dissatisfaction and undertreatment of pain. Ultimately, this resulted in having less frequent contact with providers or changing providers. CONCLUSIONS: Findings demonstrate a discordance in the expected process and content of the clinical interaction between LEP Hmong patients and providers, suggesting the need for culturally appropriate pain assessments in this population.

Reduced TRPM8 expression underpins reduced migraine risk and attenuated cold pain sensation in humans.

Multiple genome-wide association studies have identified non-coding single-nucleotide variants (SNVs) near (e.g., rs10166942[C]) or within (rs17862920[T]) the TRPM8 gene that encodes a cold thermosensor is associated with reduced migraine risk. Furthermore, rs10166942[C]) and rs10166942[T]) are more prevalent in populations that reside in hotter and colder climates, respectively. Here we assessed whether these alleles affect TRPM8 expression in humans and human physiologic responses to cold challenge. Here we show that TRPM8 expression is decreased from the chromosome harboring the rs10166942[C] allele in the human dorsal root ganglia. Moreover, carriers of rs10166942[C] required significantly lower temperatures and longer duration of exposure to reach a cold pain threshold (CPTh), which correlated with decreased TRPM8 expression expected in the carriers. This study provides evidence for a genotype-dependent influence on cold pain sensation suggesting that carriers of the reduced migraine risk allele have reduced sensitivity to cold stimuli and that TRPM8 acts as a cold thermosensor and cold pain transducer in humans. Reduced TRPM8 expression and function underpins the migraine protection in carriers of rs10166942[C]; thus, the evaluation of TRPM8 antagonists as migraine therapeutics is warranted. Furthermore, these results provide mechanistic insights for evolutionary positive selection of rs10166942[T] allele in adaptation along latitudinal cline to colder climates.

Beta-blocker Use is Associated with a Reduction in Opioid Use 30 Days After Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) can lead to chronic pain and prolonged postoperative opioid use. There are few evidence-based interventions to prevent these outcomes. Recently, beta-blockers have emerged as possible novel analgesics. OBJECTIVES: The objective of this study was to determine whether perioperative beta-blocker use is associated with reduced prolonged postoperative opioid use after TKA. STUDY DESIGN: This study used a retrospective cohort design. SETTING: The research took place within Department of Veterans Affairs hospitals in the United States between April 2012 and April 2016. METHODS: Patients: IRB approval was obtained to examine the records of Veterans Affairs (VA) patients undergoing TKA. Patients using opioids 60 days before surgery were excluded. INTERVENTION: The intervention being investigated was perioperative beta-blocker use, overall and by class. MEASUREMENT: Oral morphine equivalent usage through postoperative day 1 and prescription opioid refills through 30, 90, and 365 days after TKA were recorded. Adjusted models were created controlling for relevant demographic and comorbidity covariates. A secondary analysis examined the same outcomes separated by beta-blocker class. RESULTS: The cohort was 93.8% male with a mean age of 66 years. Among the 11,614 TKAs that comprised the cohort, 2,604 (22.4%) were performed on patients using beta-blockers. After adjustment, beta-blocker use was associated with reduced opioid use through 30 days after surgery (odds ratio [OR] 0.89 [95% confidence interval (CI), 0.80-0.99], P = .026). Selective beta-blockers were associated with reduced opioid use at 30 days (OR 0.88 [95% CI, 0.78-0.98], P = .021), and nonselective beta-blockers were associated with reduced oral morphine equivalent usage through postoperative day 1 (beta = -17.9 [95% CI, -29.9 to -5.8], P = .004). LIMITATIONS: Generalizability of these findings is uncertain, because this study was performed on a cohort of predominantly white, male VA patients. This study also measured opioid use, but opioid use is not a perfect surrogate for pain. Nevertheless, opioid use offers value as an objective measure of pain persistence in a national cohort for which patient-reported outcomes are otherwise unavailable. CONCLUSIONS: Perioperative beta-blocker use was associated with reduced prescription opioid use at 30 days after surgery. Both selective and nonselective beta-blockers were associated with reduced opioid use when analyzed individually. KEY WORDS: Analgesics, opioid, arthroplasty, replacement, knee, adrenergic beta-antagonists, pain management.

Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes.

BACKGROUND: Glucocorticoid drugs are highly effective anti-inflammatory agents, but chronic use is associated with extensive pharmacodynamic safety concerns that have a considerable negative impact on patient quality of life. PURPOSE: Vamorolone (VBP15) is a first-in-class steroidal multi-functional drug that shows potent inhibition of pro-inflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor, high affinity antagonism for the mineralocorticoid receptor, and membrane stabilization properties. Pre-clinical data in multiple mouse models of inflammation showed retention of anti-inflammatory efficacy, but loss of most or all side effects. EXPERIMENTAL APPROACH: We report first-in-human Phase 1 clinical trials (86 healthy adult males), with single ascending doses (0.1-20.0 mg/kg), and multiple ascending doses (1.0-20 mg/kg/day; 14 days treatment). KEY RESULTS: Vamorolone was well-tolerated at all dose levels. Vamorolone showed pharmacokinetic and metabolism profiles similar to prednisone. Biomarker studies showed loss of side effects of traditional glucocorticoid drugs (bone fragility, metabolic disturbance, immune suppression). Suppression of the adrenal axis was 10-fold less than prednisone. The crystallographic structure of vamorolone was solved, and compared to prednisone and dexamethasone. There was overlap in structure, but differences in conformation at the C-ring where glucocorticoids interact with Asn564 of the glucocorticoid receptor. The predicted loss of Asn564 binding to vamorolone may underlie the loss of gene transcriptional activity. CONCLUSIONS AND INTERPRETATIONS: Vamorolone is a dissociative steroid that retains high affinity binding and nuclear translocation of both glucocorticoid (agonist) and mineralocorticoid (antagonist) receptors, but does not show pharmacodynamic safety concerns of existing glucocorticoid drugs at up to 20 mg/kg/day.

Effect of Baseline Characteristics on the Pain Response to Pregabalin in Fibromyalgia Patients with Comorbid Depression.

Objective: To evaluate the effect of baseline characteristics on the treatment response to pregabalin in fibromyalgia (FM) patients with depression. Design: Post hoc analysis from a randomized, double-blind, placebo-controlled, two-way crossover study of pregabalin (300 or 450 mg/day, twice daily). Subjects: A total of 193 FM patients taking an antidepressant for comorbid depression. Methods: The effect of patient baseline characteristics on the treatment response to pregabalin vs placebo was assessed for the primary efficacy end point (mean pain score on an 11-point numeric rating scale). Variables were analyzed using a linear mixed effects model with sequence, period, and treatment as fixed factors, and subject within sequence and within subject error as random factors. Results: Pregabalin significantly improved mean pain scores vs placebo irrespective of age, duration of FM, number of prior FM medications, depression diagnosis, shorter-term depression (<10 years), prior or no prior opioid use, pain severity, anxiety severity, and sleep disruption severity (all P < 0.05). Compared with placebo, pregabalin did not significantly affect mean pain scores in patients with comorbid insomnia, irritable bowel syndrome, or gastroesophageal reflux disease; severe FM; a diagnosis of depression before FM, longer-term depression (≥ 10 years), more severe depression, or who were taking a high dose of antidepressant. Conclusions: Pregabalin significantly improved mean pain scores when compared with placebo for the majority of baseline characteristics assessed in FM patients taking an antidepressant for comorbid depression.

Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial).

Neublastin (BG00010) is a first-in-class, glial cell-derived neurotrophic factor shown in preclinical studies and an early clinical trial to have potential for the treatment of neuropathic pain. SPRINT was a phase 2, multicenter, double-blinded, placebo-controlled study to evaluate efficacy/safety of 5 neublastin doses (50, 150, 400, 800, and 1200 µg/kg) administered as an intravenous injection 3 times/week for 1 week in patients with chronic painful lumbosacral radiculopathy, utilizing Bayesian response-adaptive study design. Primary endpoint was change from baseline in mean 24-hour average general pain intensity over a 5-day period (week 1) after the last dose, analyzed using a Bayesian normal dynamic linear model. One hundred seventy-six patients were randomized and received treatment (placebo n = 48, 50 µg/kg n = 38, 150 µg/kg n = 13, 400 µg/kg n = 16, 800 µg/kg n = 20, 1200 µg/kg n = 41). Among the tested neublastin doses, the lowest dose (50 µg/kg) showed the greatest difference from placebo for change from baseline in mean average general pain intensity at week 1 after last dose, followed by the highest dose (1200 µg/kg) (posterior mean difference -1.36 [95% credible interval -2.22 to -0.52] and -0.75 [-1.59 to 0.08], respectively). Similar trends were observed in secondary efficacy endpoints. The most common adverse event in all neublastin dose groups was pruritus (79% vs 10% with placebo). There was no dose-response relationship with respect to primary/secondary efficacy outcomes or incidence of pruritus, despite dose-proportional increases in serum neublastin concentrations. In conclusion, while this study showed some evidence of pain relief with neublastin, particularly at the lowest dose, there was no clear dose-response relationship for pain reduction or the most common adverse event of pruritus.

Development and validation of Arabic version of the Neuropathic Pain Questionnaire-Short Form.

INTRODUCTION: The Neuropathic Pain Questionnaire-Short Form (NPQ-SF) is the shortest diagnostic tool for the assessment of neuropathic pain, designed with the goal to differentiate between neuropathic and nonneuropathic pain. The aim of this study was to translate, culturally adapt, and validate the NPQ-SF questionnaire in Arabic. METHODS: A systematic translation process was used to translate the original English NPQ-SF into Arabic. After the pilot study, the Arabic version was validated among patients with chronic pain in two tertiary care centers. Reliability of the translated version was examined using internal consistency, test-retest reliability, and intraclass correlation coefficient (ICC). We examined the validity of the Arabic NPQ-SF via construct validity, concurrent validity (associations with the numeric pain scale, Brief Pain Inventory, and Self-completed Leeds Assessment of Neuropathic Symptoms and Signs [S-LANSS]), face validity, and diagnostic validity. To investigate the responsiveness, the translated NPQ-SF questionnaire was administered twice among the same group of patients. RESULTS: A total of 142 subjects (68 men, 74 women) were included in the study. Cronbach's α were 0.45 (95% CI: 0.29, 0.61) and 0.48 (95% CI: 0.33, 0.63), and the ICC was 0.78 (95% CI: 0.72, 0.85). The NPQ-SF was moderately to strongly associated with the S-LANSS questionnaire. Results showed our Arabic NPQ-SF to have good diagnostic accuracy, with area under the curve of 0.76 (95% CI: 0.67, 0.84). Results from the receiver operating characteristic analysis identified a cut-off score of ≥0.52 as the best score to distinguish between patients with or without neuropathic pain, which was higher than the recommended cut-off score (≥0) in the original study. With both sensitivity and specificity of 71%. Most patients found the NPQ-SF questionnaire to be clear and easy to understand. CONCLUSION: Our translated version of NPQ-SF is reliable and valid for use, thus providing physicians a new tool with which to evaluate and diagnose neuropathic pain among Arabic-speaking patients.

Pregabalin for the Treatment of Drug and Alcohol Withdrawal Symptoms: A Comprehensive Review.

Treatments for physical dependence and associated withdrawal symptoms following the abrupt discontinuation of prescription drugs (such as opioids and benzodiazepines), nicotine, alcohol, and cannabinoids are available, but there is still a need for new and more effective therapies. This review examines evidence supporting the potential use of pregabalin, an α2δ voltage-gated calcium channel subunit ligand, for the treatment of physical dependence and associated withdrawal symptoms. A literature search of the MEDLINE and Cochrane Library databases up to and including 11 December 2015 was conducted. The search term used was '(dependence OR withdrawal) AND pregabalin'. No other date limits were set and no language restrictions were applied. Works cited in identified articles were cross-referenced and personal archives of references also searched. Articles were included based on the expert opinions of the authors. There is limited evidence supporting the role of pregabalin for the treatment of physical dependence and accompanying withdrawal symptoms associated with opioids, benzodiazepines, nicotine, cannabinoids, and alcohol, although data from randomized controlled studies are sparse. However, the current evidence is promising and provides a platform for future studies, including appropriate randomized, placebo- and/or comparator-controlled studies, to further explore the efficacy and safety of pregabalin for the treatment of withdrawal symptoms. Given the potential for pregabalin misuse or abuse, particularly in individuals with a previous history of substance abuse, clinicians should exercise caution when using pregabalin in this patient population.