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.

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.

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.

"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.

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.

Mindfulness Meditation and Cognitive Behavioral Therapy Intervention Reduces Pain Severity and Sensitivity in Opioid-Treated Chronic Low Back Pain: Pilot Findings from a Randomized Controlled Trial.

OBJECTIVE: To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain (CLBP). DESIGN: 26-week parallel-arm pilot randomized controlled trial (Intervention and Usual Care versus Usual Care alone). SETTING: Outpatient. SUBJECTS: Adults with CLBP, prescribed ≥30 mg/day of morphine-equivalent dose (MED) for at least 3 months. METHODS: The intervention comprised eight weekly group sessions (meditation and CLBP-specific CBT components) and 30 minutes/day, 6 days/week of at-home practice. Outcome measures were collected at baseline, 8, and 26 weeks: primary-pain severity (Brief Pain Inventory) and function/disability (Oswestry Disability Index); secondary-pain acceptance, opioid dose, pain sensitivity to thermal stimuli, and serum pain-sensitive biomarkers (Interferon-γ; Tumor Necrosis Factor-α; Interleukins 1ß and 6; C-reactive Protein). RESULTS: Thirty-five (21 experimental, 14 control) participants were enrolled and completed the study. They were 51.8 ± 9.7 years old, 80% female, with severe CLBP-related disability (66.7 ± 11.4), moderate pain severity (5.8 ± 1.4), and taking 148.3 ± 129.2 mg/day of MED. Results of the intention-to-treat analysis showed that, compared with controls, the meditation-CBT group reduced pain severity ratings during the study (P = 0.045), with between-group difference in score change reaching 1 point at 26 weeks (95% Confidence Interval: 0.2,1.9; Cohen's d = 0.86), and decreased pain sensitivity to thermal stimuli (P < 0.05), without adverse events. Exploratory analyses suggested a relationship between the extent of meditation practice and the magnitude of intervention benefits. CONCLUSIONS: Meditation-CBT intervention reduced pain severity and sensitivity to experimental thermal pain stimuli in patients with opioid-treated CLBP.

Intravenous abuse potential study of oxycodone alone or in combination with naltrexone in nondependent recreational opioid users.

BACKGROUND: ALO-02, comprising pellets of extended-release oxycodone surrounding sequestered naltrexone, is intended to deter abuse. OBJECTIVE: Determine the abuse potential of intravenous oxycodone combined with naltrexone, which represents simulated crushed ALO-02 in solution, compared with intravenous oxycodone in nondependent, recreational opioid users. METHODS: A randomized, double-blind, placebo-controlled, three-way crossover study with naloxone challenge, drug discrimination, and treatment phases. Intravenous treatments included oxycodone hydrochloride 20 mg, oxycodone hydrochloride 20 mg plus naltrexone hydrochloride 2.4 mg (simulated crushed ALO-02 20 mg/2.4 mg), or placebo (0.9% sodium chloride for injection). Primary end points were peak effects (Emax) and area under the effects curve within 2 h postdose (AUE0-2h) on drug liking and high visual analog scales. RESULTS: Thirty-three participants were randomized into treatment phase, and 29 completed all treatments. Study validity was confirmed with statistically significant differences in Emax for drug liking and high (p < 0.0001) between intravenous oxycodone and placebo. Intravenous simulated crushed ALO-02 resulted in significantly lower scores than oxycodone on drug liking (Emax: 58.2 vs. 92.4; AUE0-2h: 104.3 vs. 152.4) and high (Emax: 17.2 vs. 93.1; AUE0-2h: 12.0 vs. 133.6), respectively (p < 0.0001, all comparisons). More participants experienced adverse events after intravenous oxycodone (n = 27 [90%]) versus intravenous simulated crushed ALO-02 (n = 4 [12.5%]) or placebo (n = 2 [6.5%]). CONCLUSION: Intravenous administration of simulated crushed ALO-02 resulted in significantly lower abuse potential, as assessed by subjective ratings of drug liking and high, than intravenous oxycodone in nondependent, recreational opioid users. This suggests that injection of ALO-02 may not be as desirable to recreational opioid users compared with oxycodone taken for nonmedical reasons.

Are Pain Ratings Irrelevant?

Pain intensity ratings have been the basis of pain diagnosis and a fundamental tool in pain research, but are not always used. Frequent comments by physicians that pain ratings, sometimes called pain scores, are not useful in clinical practice and comments by basic scientists that pain ratings may measure the wrong thing, have been in significant part supported by a short survey conducted among members of American Pain Society (APS). Though limited by small number of respondents, the findings of this survey and additional comments by members of APS raise critical questions about why pain ratings do not serve the clinical communities. These findings send an urgent call to the pain community to reassess the status of currently used pain ratings and to find solutions to this fundamental issue.

Intravenous lidocaine for neuropathic pain: a retrospective analysis of tolerability and efficacy.

OBJECTIVES: This study was designed to describe the efficacy and toxicity of intravenous (i.v.) lidocaine infusions for the treatment of neuropathic pain initially administered at a flat-rate trial dose of 500 mg over 30 minutes. SETTING: Academic, tertiary care hospital and infusion center. METHODS: Data were retrospectively collected and analyzed for efficacy, correlations between infusion rates with adverse effects, patterns of infusion rate adjustments, and infusion frequencies. RESULTS: The average rate for all infusions was 9.1 mg/min. Efficacy was seen in 45 patients (65%), and all but eight patients (12%) required infusion rate reductions from the initial test rate of 16.7 mg/min due to adverse effects. Fifty-five patients experienced adverse effects, with light-headedness as the most frequently reported side effect. CONCLUSION: The flat-dose trial used under the University of Wisconsin Health protocol for i.v. lidocaine administration did not cause serious adverse events, but few patients who responded to this trial dose tolerated subsequent infusions at the trial rate. Due to the lack of serious adverse events, administering an aggressive trial dose to elicit an analgesic response appears to be rational. If patients show a benefit from the trial dose, the need for reductions in infusion rate of subsequent doses should be anticipated.

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).

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.

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.

Review of neuropathic pain screening and assessment tools.

Chronic pain due to injury to or diseases of the nervous system, known as neuropathic pain (NP), is a common debilitating medication condition for which there are currently several symptomatically effective therapies. Therefore, early identification of NP in the primary and specialty care setting will avoid unnecessary delays in amelioration of symptoms. Given that it is associated with unique symptoms and physical exam signs, several assessment tools have been developed to aid medical practitioners in the identification of patients with NP. The majority of these tools have been developed to differentiate NP from nonNP and to quantify the severity of symptoms that define NP, and some have been used to aid in assessment of response to interventions. This focused review will describe the primary NP assessment tools that are currently available, and discuss their suitability for screening patients and for research applications. Wider use of NP assessment tools will facilitate the development of new therapies, further clarify the epidemiology of this condition, and improve the treatment of NP.

Turning on the alarm: the neural mechanisms of the transition from innocuous to painful sensation.

The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49°C) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid-cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum.

Neuropathic pain therapy: from bench to bedside.

Neuropathic pain is a result of complex interactions between peripheral and central mechanisms with multiple potential therapeutic targets. However, the complexity of these mechanisms and relative youth of translational pain research, which is in its infancy, have prevented translation of successful basic bench research to human therapy. Most of the clinically available neuropathic pain treatments are borrowed from other therapeutic areas, such as antidepressants and antiepileptics, or involve application of older therapy, such as opioids. Exceptions are ziconotide, tapentadol, and the high-concentration capsaicin patch. Similar to all other analgesic agents, these provide only partial pain relief in subsets of patients. The standard of care for patients with chronic neuropathic pain is multimodal and multidisciplinary. For most patients to achieve and maintain satisfactory pain relief a combination of therapeutic agents is necessary, providing the empiric basis for rational polypharmacy, which has become a standard approach as well.

Cognitive outcome of cerebral fat embolism.

Cerebral fat embolism is an uncommon but serious complication of long-bone fracture. We report a young adult patient who sustained fat embolism after a femoral fracture. He developed stupor and coma within 24 hours from his injury. His acute recovery was characterized by marked frontal dysfunction. A comprehensive neuropsychological evaluation 4 months later revealed overall normal cognitive function, except for mild residual frontal dysfunction and weakness of verbal memory.

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.

Evidence-based guideline: treatment of painful diabetic neuropathy--report of the American Association of Neuromuscular and Electrodiagnostic Medicine, the American Academy of Neurology, and the American Academy of Physical Medicine & Rehabilitation.

The objective of this report was to develop a scientifically sound and clinically relevant evidence-based guideline for the treatment of painful diabetic neuropathy (PDN). The basic question that was asked was: "What is the efficacy of a given treatment (pharmacological: anticonvulsants, antidepressants, opioids, others; non-pharmacological: electrical stimulation, magnetic field treatment, low-intensity laser treatment, Reiki massage, others) to reduce pain and improve physical function and quality of life (QOL) in patients with PDN?" A systematic review of literature from 1960 to August 2008 was performed, and studies were classified according to the American Academy of Neurology classification of evidence scheme for a therapeutic article. Recommendations were linked to the strength of the evidence. The results indicate that pregabalin is established as effective and should be offered for relief of PDN (Level A). Venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids (morphine sulfate, tramadol, and oxycodone controlled-release), and capsaicin are probably effective and should be considered for treatment of PDN (Level B). Other treatments have less robust evidence, or the evidence is negative. Effective treatments for PDN are available, but many have side effects that limit their usefulness. Few studies have sufficient information on their effects on function and QOL.

Gynecologic management of neuropathic pain.

Obstetrician/gynecologists often are the initial management clinicians for pelvic neuropathic pain. Although treatment may require comprehensive team management and consultation with other specialists, there are a few critical and basic steps that can be performed during an office visit that offer the opportunity to improve quality of life significantly in this patient population. A key first step is a thorough clinical examination to map the pain site physically and to identify potentially involved nerves. Only limited evidence exists about how best to manage neuropathic pain; generally, a combination of surgical, manipulative, or pharmacologic methods should be considered. Experimental methods to characterize more precisely the nature of the nerve dysfunction exist to diagnose and treat neuropathic pain; however, additional scientific evidence is needed to recommend these options unanimously. In the meantime, an approach that was adopted from guidelines of the International Association for the Study of Pain has been tailored for gynecologic pain.