Quantitative Sensory Testing In Patients Research Articles

N-Check: nerve check to document chemotherapy-induced peripheral neuropathy (CIPN) in incurable cancer

Chemotherapy-induced polyneuropathy (CIPN) encompasses aspectrum of symptoms ranging from hypoesthesia with impaired gait, stance and fine motor skills to painful dysesthesia and allodynia and significantly impairs the quality of life of those affected. In the present pilot study, quantitative sensory testing (QST) was used to investigate CIPN as acommon adverse effect of cytostatic drugs in patients with incurable cancer. The QST is astandardized examination procedure that is not yet routinely used in cancer patients. It is used to examine thermal and mechanical perception and pain thresholds to record the subjectively experienced pain phenotype. In the N‑Check pilot project, the QST was used before and after tumor-specific, potentially CIPN-inducing treatment and the data collected was compared in apre-post analysis. In addition, the specific effects of CIPN on the health-related quality of life of patients treated primarily with apalliative intention were recorded using the Functional Assessment for Cancer Therapy-General (FACT-G) questionnaire. Overall, the patients showed significant heat hypoalgesia after chemotherapy as asign of damage to small nerve fibers. In addition, there were signs of deterioration of the quality of life. The feasibility of QST in patients with incurable cancer and palliative, neurotoxic chemotherapy was demonstrated in this pilot study.

Sex Differences in Pain and Quantitative Sensory Testing in Patients With Rheumatoid Arthritis.

Women with rheumatoid arthritis (RA) have higher pain and worse functional outcomes compared to men, even when treated with similar medications. The objective of this study was to identify sex differences in pain intensity, pain interference, and quantitative sensory tests (QST), which are independent of inflammation, in patients with RA. This study is a post hoc analysis of participants in the Central Pain in Rheumatoid Arthritis cohort. Pain intensity was assessed using a 0-10 numeric rating scale. Pain interference was measured using a Patient-Reported Outcomes Measurement Information System computerized adaptive test. QST included pressure pain detection thresholds, temporal summation, and conditioned pain modulation. Women and men were compared using multiple linear regression, adjusted for age, education, race, research site, depression, obesity, RA disease duration, swollen joint count, and C-reactive protein. Mean ± SD pain intensity was 5.32 ± 2.29 among women with RA, compared to 4.60 ± 2.23 among men with RA (adjusted difference 0.83 [95% confidence interval (95% CI) 0.14, 1.53]). Women with RA had lower pressure pain detection thresholds at the trapezius (adjusted difference -1.22 [95% CI -1.73, -0.72]), wrist (adjusted difference -0.57 [95% CI -1.07, -0.06]), and knee (adjusted difference -1.10 [95% CI -2.00, -0.21]). No statistically significant differences in pain interference, temporal summation, and conditioned pain modulation were observed. Women reported higher pain intensity and lower pressure pain detection thresholds (higher pain sensitivity) than men. However, pain interference, temporal summation, and conditioned pain modulation did not differ between men and women.

Altered central pain processing assessed by quantitative sensory testing in patients with failed back surgery syndrome

ObjectiveTo investigate the presence of altered central pain processing in patients with failed back surgery syndrome (FBSS) using quantitative sensory testing (QST). MethodsThis study included 34 patients with FBSS, 102 patients post-lumbar surgery without low back pain (LBP), and 102 healthy subjects. All subjects underwent both pressure pain threshold (PPT) and conditioned pain modulation (CPM) in both local and remote pain-free areas, as well as temporal summation (TS) in a remote pain-free area. All patient subjects were assessed using the Pain Catastrophizing Scale (PCS), Beck Anxiety Inventory (BAI), Beck Depression Index (BDI), Numeric rating pain scale (NRS) and Oswestry Disability Index (ODI). ResultsCompared with both control groups, FBSS patients showed a reduction in both PPT and CPM in both tested areas, along with increased TS in a pain-free area (P < 0.05). Furthermore, the patients with FBSS had a significantly higher prevalence of anxiety, depression and pain catastrophizing thoughts than the patient controls (P < 0.05). In the FBSS patients, there was a significant correlation between LBP at rest and both CPM and TS in the pain-free areas, and QST measurements were also associated with the ODI, PCS and BAI (P < 0.05). ConclusionThese findings support the existence of augmented central pain processing in patients with FBSS, which may be caused by dysfunction of endogenous pain facilitation and inhibition. This central amplification of pain may contribute to both LBP intensity and disability in FBSS patients. Therefore, treatment efforts should take into account functional alterations in the central nervous system of FBSS patients.

Neuroendocrine effects of a single bout of functional and core stabilization training in women with chronic nonspecific low back pain: A crossover study.

Exercise‐induced hypoalgesia (EIH) is characterized as the pain reduction after an exercise session and it seems to be related to the release of plasma β‐endorphin. In this sense, the core stabilization training (CT) has been suggested for patients with chronic nonspecific low back pain (CNSLBP), but it is unclear whether it induces EIH. Patients with CNSLBP have neuromotor dysfunctions that can affect the performance of functional tasks, thus, performing functional training (FT) could improve motor control and promote EIH, since functional training uses multi‐joint exercises that aim to improve the functionality of actions performed in daily life. EIH is usually assessed using quantitative sensory tests (QST) such as conditioned pain modulation, pressure pain threshold, and temporal summation. Thus, the sum of parameters from quantitative sensory tests and plasma β‐endorphin would make it possible to understand what the neuroendocrine effects of FT and CT session are. Our study compared the acute effect of CT and FT on the EIH and plasma β‐endorphin release, and correlated plasma β‐endorphin with quantitative sensory testing in patients with CNSLBP. Eighteen women performed two training sessions (CT and FT) with an interval of 48 h between sessions. EIH was assessed by QST and plasma β‐endorphin levels. Results showed that only FT significantly increased plasma β‐endorphin (FT p < 0.01; CT p = 0.45), which correlated with pain pressure threshold (PPT) and conditioned pain modulation (CPM). However, QST values were not different in women with CNSLBP after CT or FT protocols. Plasma β‐endorphin correlated with PPT and CPM, however, the same did not occur with a temporal summation.

Thermal grill illusion of pain in patients with chronic pain: a clinical marker of central sensitization?

The thermal grill illusion of pain (TGIP) is a paradoxical burning pain sensation elicited by the simultaneous application of innocuous cutaneous warm and cold stimuli with a thermode ("thermal grill") consisting of interlaced heated and cooled bars. Its neurophysiological mechanisms are unclear, but TGIP may have some mechanisms in common with pathological pain, including central sensitization in particular, through the involvement of N-methyl- d -aspartate receptors. However, few studies have investigated TGIP in patients with chronic pain and its clinical relevance is uncertain. We hypothesized that the TGIP would be increased in comparison with controls in patients with fibromyalgia or irritable bowel syndrome, which are regarded as typical "nociplastic" primary pain syndromes related to changes in central pain processing. We compared the sensations elicited by a large range of combinations of temperature differentials between the warm and cold bars of a thermal grill applied to the hand between patients with fibromyalgia (n = 30) or irritable bowel syndrome (n= 30) and controls (n = 30). The percentage of TGIP responses and the intensity and unpleasantness of TGIP were significantly greater in patients than controls. Furthermore, positive correlations were found between TGIP intensity and clinical pain intensity and between TGIP intensity and the cold pain threshold measured on the hand. These results are consistent with our working hypothesis of shared mechanisms between TGIP and clinical pain mechanisms in patients with nociplastic chronic pain syndromes and suggest that TGIP might represent a clinical marker of central sensitization in these patients.

Cutaneous allodynia and thermal thresholds in chronic migraine: The effect of onabotulinumtoxinA

ObjectiveCutaneous allodynia (CA) is a common symptom in migraine. Its incidence is more frequent in the chronic migraine (CM). CA usually occurs during pain attacks. However, it can also be interictal and its frequency and severity seem to be correlated with the duration of the disease. Several quantitative sensory testing (QST) studies have revealed variable results about mechanical and thermal allodynia accompanying migraine. This study aimed to investigate the effects of CA and onabotulinumtoxinA (BoNT-A) injection on the thermal thresholds measured by QST in patients with CM. The effects of BoNT-A on headaches, CA, and other accompanying symptoms of migraine were also evaluated. MethodsSingle BoNT-A injections were performed in 22 female cases (mean age: 38.1 ± 7.2 years) with CM. Patients were evaluated at 1–7 days before, 28–35, and 84–91 days after the injection. The 22 healthy women in the control group (mean age: 36.6 ± 7.6 years) were examined once. Headache and its characteristics, medication intake, allodynia, presence of anxiety, and depression symptoms were evaluated through relevant scales. The heat (HDT) and cold (CDT) detection thresholds on the forehead and hand were measured bilaterally with QST. The presence of brush allodynia for patients was examined by applying a 4 × 4 gauze pad over the same areas. ResultsThe patients in the CM group had migraine for an average of 22.5 ± 6.1 years and CM for 6.1 ± 3.2 years. The average number of painful days per month was 22.1 ± 4.0 days. All the patients had migraine attacks with CA (mean 5.6/month). The average allodynia symptom checklist (ASC-12) score was 7.8 ± 6.2. Thermal thresholds measured in the patients with CM were similar to those of the controls. Thermal thresholds did not show significant differences between the symptomatic and the asymptomatic sides at the last migraine attack. There was also no correlation between the allodynia revealed by the physical examination and the thermal thresholds detected by QST. The ASC-12 score decreased significantly with BoNT-A injection (p = 0.030), but no significant change was observed in thermal thresholds after this treatment. ConclusionThere was no significant correlation between CA and thermal thresholds. BoNT-A was successful in relieving headache and other associated symptoms, including CA, but had no significant effect on QST parameters.

Changes in quantitative sensory testing and patient perspectives following spinal cord stimulation for persistent spinal pain syndrome: An observational study with long-term follow-up.

BackgroundSpinal cord stimulation (SCS) can impact sensory, pain and tolerance thresholds in various ways, which can be accessed via quantitative sensory testing (QST). The objectives of this study were to (1) assess the subjective sensory responses using QST in patients following SCS therapy for PSPS and (2) to get a clinical impression of the results of SCS during an interview of these patients with PSPS and SCS during long term follow‐up.MethodsForty patients with PSPS who received SCS treatment underwent QST via electrical and mechanical pressure stimuli. QST was performed at four different moments (1) pre‐implantation SCS, (2) two weeks postoperatively, (3) three months after permanent SCS implantation and (4) six months after permanent SCS implantation. Patients’ perspectives on pain, use of drugs and quality of life were assessed via semi‐structured interviews during a follow‐up between 5 and 11 years.ResultsWe found statistical significant differences in the changes of sensory, pain and tolerance thresholds. A decrease in pain complaints and analgesics use were reported by the patients during follow‐up. The quality of life in patients increased from three to eight (NRS 0 [worst QoL imaginable] ‐10 [best QoL imaginable]) after receiving SCS.ConclusionsThe increased thresholds on areas without pain or being covered by the SCS induced paresthesias may indicate that there are central changes contributing to these deviations in thresholds. The overall QoL in patients improved greatly after receiving SCS.SignificanceThis study provides an overview of the effect of SCS on sensory, pain and tolerance thresholds in patients with PSPS throughout the SCS treatment process. In addition, this study presents data from 40 patients with PSPS treated with SCS, analysing several long‐term patient‐reported outcome measures. The results serve to give more insight into the mechanism of SCS and document SCS as a possible treatment for PSPS.

Correlation of Fibromyalgia Survey Questionnaire and Quantitative Sensory Testing Among Patients With Active Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) commonly demonstrate disordered pain processing associated with high pain sensitization. Pain sensitization is often assessed using quantitative sensory testing (QST), which is burdensome to patients. The self-administered Fibromyalgia Survey Questionnaire (FSQ) has been proposed as a low-burden, surrogate measure of central pain sensitization. We examined the correlation between FSQ and QST in patients with active RA. Participants in the Central Pain in Rheumatoid Arthritis (CPIRA) cohort underwent FSQ and QST evaluation at enrollment. QST measures included pressure pain threshold (PPT) at the thumb, trapezius, wrist, and knee; temporal summation (TS) at the wrist and arm; and conditioned pain modulation (CPM). Partial Spearman correlation between FSQ and each QST measure was assessed, adjusted for demographic factors, study site, disease characteristics, and pain catastrophizing. Sensitivity analyses included (1) stratified analysis by sex and (2) evaluation of how each component of FSQ associates with the QST measures. Among 285 participants with active RA, FSQ was weakly but statistically significantly correlated with PPT (r range = -0.31 to -0.21), and TS (r range = 0.13-0.15) at all sites in unadjusted analyses. After adjustment, statistically significant correlations persisted for TS at the wrist and PPT at all sites (except the thumb). Sensitivity analyses did not identify differences in association based on sex or with individual FSQ components. FSQ and QST were correlated among participants with active RA, but the strength of association was weak. QST and FSQ are not interchangeable measures of pain sensitization.

Are Reports of Pain, Disability, Quality of Life, Psychological Factors, and Central Sensitization Related to Outcomes of Quantitative Sensory Testing in Patients Suffering From Chronic Whiplash Associated Disorders?

Chronic whiplash associated disorders (CWAD) are characterized by long-lasting symptoms of neck pain occurring after an acceleration-deceleration injury. Central sensitization (CS) has been suggested as the possible underlying mechanism for these symptoms, and is characterized by changes in the central nervous system. Besides CS, psychological factors are believed to play an important role in the experience of (chronic) pain. Investigatingthe relationships between self-reported pain, disability, quality of life, psychological factors, and symptoms of CS; and electrical-based quantitative sensory testing (QST) outcomesin CWAD patients. Secondly, to investigate the differences in QST between CWAD patients and pain-free controls. Seventy-two individuals with CWAD and 55 pain-free controls underwent electrical stimuli-based QST. Detection and pain thresholds (EPT), temporal summation (TS), and conditioned pain modulation were examined. Spearman correlation and linear mixed models analyses were performed to assess, respectively, the hypothesized associations and group differences in QST. The Pain Catastrophizing magnification subscale correlated with the left wrist EPT (r=-0.332; P=0.004), and the Pain Anxiety Symptom Scale-20 with the left wrist (r=-0.325; P=0.005) and ankle (r=-0.330; P=0.005) EPT. TS at the ankle correlated with the CS inventory (r=0.303; P=0.010), Short Form 36 pain subscale (r=-0.325; P=0.005), and Illness Perception Questionnaire revised consequences subscale (r=0.325; P=0.005). EPTs left (P=0.011) and right wrist (P=0.023) were lower in the CWAD group, but conditioned pain modulation and TS did not differ between groups. QST outcomes relate to psychological constructs, rather than to self-reported pain intensity and distribution. Local hyperalgesia was found in individuals with CWAD, but no differences in endogenous pain facilitation nor inhibition.

Quantitative sensory testing in patients with the muscle pain subtype of temporomandibular disorder: a systemic review and meta-analysis.

This meta-analysis aimed to evaluate quantitative sensory testing (QST) evidence for pain processing in patients with the muscle pain subtype of temporomandibular disorders (mTMD). A comprehensive systematic electronic search strategy was performed in online literature databases. All full-text observational studies published up to July 2021 with the aim of investigating pain sensitization in humans with mTMD using QST measures were eligible for inclusion. Meta-analysis of QST data was performed using a random effects model, which included results comparing patients with mTMD to healthy controls, and standard mean difference (SMD) results were analyzed. Twelve studies with 732 participants (371 patients with mTMD and 361 healthy controls) were analyzed following screening and quality appraisal. Compared with healthy controls, patients with mTMD had significantly lower pressure pain threshold (SMD - 1.10, 95% confidence interval [CI] - 1.52 to - 0.68) with high heterogeneity (Tau2 = 0.61, I2 = 86%), and significantly lower mechanical pain threshold (SMD - 0.64, 95% CI - 0.95 to - 0.32) with no heterogeneity (Tau2 = 0.00, I2 = 0%). No difference was observed in the cold pain threshold (SMD 0.16, 95% CI - 0.13 to 0.45), heat pain threshold (SMD - 0.13, 95% CI - 0.40 to 0.15), and wind-up ratio (SMD 0.63, 95% CI - 0.11 to 1.38) between patients with mTMD and healthy controls. Other QST parameters were also discussed. The study results suggest that the pain processing of deep tissues is likely sensitized in mTMD and calls for more QST studies with standard procedures to reduce inter-study heterogeneity. The major findings of this meta-analysis support using PPT to examine the pain processing in patients with mTMD in clinical scenario.

Quantitative Sensory Testing Protocols to Evaluate Central and Peripheral Sensitization in Knee OA: A Protocol for a Scoping Review.

Quantitative sensory testing (QST) methods have become widely used for the assessment of nervous system sensitization to nociceptive signalling in studies of people with knee osteoarthritis (OA). However, few standardised QST protocols have been developed. Variability in their execution may lead to differences in their interpretation. The proposed scoping review will seek to identify various QST methodologies being used in the assessment of sensitization and how sensitization is being defined in people with knee OA. Methods and Analysis: This scoping review will be guided by existing scoping review methodologies. Relevant studies will be extracted from the following electronic databases: Medical Literature Analysis and Retrieval System Online, ExcerptaMedica Database, Allied and Complementary Medicine Database and the Cumulative Index to Nursing Allied Health Literature. Independent screening of the abstracts and full articles and data extraction will be performed in pairs. Information extracted will focus on qualitative and quantitative data relevant to the content of the protocols from included studies. Data will be summarised in order to draw conclusions on the common elements used in QST protocols and definitions of sensitization for knee OA. This scoping review will provide insight into the most common methods of QST used in the assessment of nociceptive signaling in people with knee OA. This will potentially identify areas where a systematic review or other primary research may be required in order to develop fixed evidence-based protocols for QST in patients with knee OA.

Profiling thermal pain using quantitative sensory testing in patients with trigeminal nerve injury.

To investigate the thermal pain phenotypes using QST in patients with unilateral trigeminal nerve injury and to explore whether these different thermal pain phenotypes are associated with clinical and psychophysical characteristics. This retrospective study included 84 patients diagnosed with posttraumatic trigeminal neuropathy involving inferior alveolar nerve (IAN) and lingual nerve (LN). Data on clinical characteristics, subjective symptoms including hypoesthesia, dysesthesia, and allodynia, and objective signs using thermal QST were collected and explored. Three heat (heat hypoalgesia, heat hyperalgesia, and within normal range) and cold pain phenotypes (cold hypoalgesia, cold hyperalgesia, and within normal ranges) were identified, respectively. Thermal hypoalgesia was more frequently observed than thermal hyperalgesia. Heat hypoalgesia regardless of cold pain abnormalities appears to be associated with subjective negative symptoms, while thermal hyperalgesia seems to have little relationship with negative and positive symptoms. Thermal pain phenotypes were associated with loss of innocuous thermal sensation. Unlike heat pain phenotypes, cold pain phenotypes differed between IAN injury and LN injury. The thermal pain phenotypes identified in this study seem to be related to clinical and psychophysical findings differently. These results would be a good starting point for assessing posttraumatic trigeminal neuropathy and interpreting the thermal QST results.

Associations between physical performances, self-reported outcomes, and quantitative sensory testing in patients with chronic pain after knee osteoarthritis and total knee arthroplasty

Associations between physical performances, self-reported outcomes, and quantitative sensory testing in patients with chronic pain after knee osteoarthritis and total knee arthroplasty

The use of quantitative sensory testing in cancer pain assessment: A systematic review.

To summarize the literature on the use of quantitative sensory testing (QST) in the assessment of pain in people with cancer and to describe which QST parameters consistently demonstrate abnormal sensory processing in patients with cancer pain. Medline, EMBASE, AMED, CINAHL, SCOPUS and CENTRAL were searched for observational or experimental studies using QST in patients with a cancer diagnosis and reporting pain. Search strategies were based on the terms "quantitative sensory testing", "cancer", "pain", "cancer pain" and "assessment". Databases were searched from inception to January 2019. Data were extracted and synthesized narratively, structured around the different QST modalities and sub-grouped by cancer pain aetiology (tumour- or treatment-related pain). Searches identified 286 records of which 18 met the eligibility criteria for inclusion. Three studies included patients with tumour-related pain, and 15 studies included patients with pain from chemotherapy-induced peripheral neuropathy (CIPN). Across all studies, 50% (9/18) reported sensory abnormities using thermal detection thresholds (cool and warm), 44% (8/18) reported abnormal mechanical detection thresholds using von-Frey filaments and 39% (7/18) found abnormal pinprick thresholds. Abnormal vibration and thermal pain (heat/cold) thresholds were each reported in a third of included studies. This systematic review highlights the lack of published data characterizing the sensory phenotype of tumour-related cancer pain. This has implications for our understanding of the underlying pathophysiological mechanisms of cancer pain. Understanding the multiple mechanisms driving cancer pain will help to move towards rational individualized analgesic treatment choices. This systematic review found that pain in cancer patients is associated with abnormal sensory responses to thermal, mechanical and pinprick stimuli. However, these findings are based primarily on studies of chemotherapy-induced peripheral neuropathy and data on tumour-related pain are lacking, warranting further research.

Erratum to: Quantitative Sensory Testing in Patients with Multisomatoform Disorder with Chronic Pain as the Leading Bodily Symptom-a Matched Case-Control Study.

OBJECTIVE Chronic pain is a debilitating condition of multifactorial origin, often without physical findings to explain the presenting symptoms. Of the possible etiologies of persisting painful symptoms, somatoform disorders and functional somatic syndromes (FSS) are among the most challenging, with a prevalence of 8-20%. Many different somatoform disorders and FSS have overlapping symptoms, with pain being the most prevalent one. The concept of multisomatoform disorder (MSD) has been developed to acknowledge that fact. We hypothesized that the concept of MSD will be reflected in a distinct sensory profile of patients compared with healthy controls and possibly provide insight into the type and pathophysiology of the pain commonly experienced by patients. DESIGN We performed comprehensive quantitative sensory testing (QST) in 151 patients and 149 matched controls. RESULTS There were significant differences in the sensory profiles of patients compared with controls. Patients with MSD showed a combination of tactile and thermal hypesthesia combined with mechanical and cold hyperalgesia. This was true for measurements at test and control sites, with the exception of vibration detection threshold and mechanical pain threshold. Among the observed changes, a marked sensory loss of function, as evidenced by an increase in cold detection threshold, and a marked gain of function, as evidenced by a decrease of pressure pain threshold, were most notable. There was no evidence of concurrent medication influencing QST results. CONCLUSIONS The observed somatosensory profile of patients with MSD resembles that of patients suffering from neuropathic pain with evidence of central sensitization.

Quantitative Sensory Testing in Patients with Multisomatoform Disorder with Chronic Pain as the Leading Bodily Symptom-a Matched Case-Control Study.

Chronic pain is a debilitating condition of multifactorial origin, often without physical findings to explain the presenting symptoms. Of the possible etiologies of persisting painful symptoms, somatoform disorders and functional somatic syndromes (FSS) are among the most challenging, with a prevalence of 8-20%. Many different somatoform disorders and FSS have overlapping symptoms, with pain being the most prevalent one. The concept of multisomatoform disorder (MSD) has been developed to acknowledge that fact. We hypothesized that the concept of MSD will be reflected in a distinct sensory profile of patients compared with healthy controls and possibly provide insight into the type and pathophysiology of the pain commonly experienced by patients. We performed comprehensive quantitative sensory testing (QST) in 151 patients and 149 matched controls. There were significant differences in the sensory profiles of patients compared with controls. Patients with MSD showed a combination of tactile and thermal hypesthesia combined with mechanical and cold hyperalgesia. This was true for measurements at test and control sites, with the exception of vibration detection threshold and mechanical pain threshold. Among the observed changes, a marked sensory loss of function, as evidenced by an increase in cold detection threshold, and a marked gain of function, as evidenced by a decrease of pressure pain threshold, were most notable. There was no evidence of concurrent medication influencing QST results. The observed somatosensory profile of patients with MSD resembles that of patients suffering from neuropathic pain with evidence of central sensitization.

Itch sensitization? A systematic review of studies using quantitative sensory testing in patients with chronic itch.

As well established for patients with chronic pain, patients suffering from chronic itch also exhibit signs of peripheral and central sensitization. This has been linked to parallel neuroplastic sensitization processes. However, for chronic itch, sensitization has not yet been systematically assessed, studied, and hence validated. This review (Prospero CRD42016043002) summarizes and meta-analytically evaluates whether sensory aberrations including sensitization for itch occur in chronic itch. Databases PubMed, Embase, and Cochrane Library were searched for studies investigating somatosensory sensitivity assessment by quantitative sensory testing stimuli, including experimental cutaneous chemical pruritic provocations, in patients with chronic itch from skin/neurological conditions and compared with healthy controls. Outcomes were extracted for lesional and nonlesional skin, and risk of biases were assessed. Meta-analyses were performed when sufficient quantitative data were available. Of 4667 identified articles, 46 were included and 25 were eligible for meta-analyses. Patients (66% atopic dermatitis [AD]) were found more sensitive than the controls to histamine-evoked itch in lesional skin (standardized mean difference [SMD]: 0.66 confidence interval [CI]: 0.16-1.15), but not nonlesionally (SMD: -0.26 [CI: -0.58 to 0.06]). Cowhage did not evoke more itch in nonlesional skin of patients as compared to the controls (SMD: 0.38 [CI: -0.04 to 0.81]). For numerous other chemical provocations as well as for mechanical, thermal, and electrical stimulation paradigms, results were ambiguous or based on few studies. Patients with chronic itch are only robustly sensitized to various chemical pruritic stimuli when applied lesionally. More studies on somatosensory aberrations in chronic itch conditions other than AD are needed to establish whether sensitization is robustly present across chronic itch conditions.

(241) Gabapentin Efficacy in Chronic and Vaso-Occlusive Crises-Induced Acute Sickle Cell Disease Pain

Pain is the leading cause of hospitalization for patients with sickle cell disease (SCD). Currently, opioids are the main therapy for both chronic “steady state” SCD pain and acute pain that results from vaso-occlusive crises. However, opioids are often ineffective at fully alleviating pain, are associated with unwanted side effects, and do not target the underlying pain mechanism. Thus, new pain therapies are desperately needed for those suffering from SCD pain. Recent quantitative sensory testing in patients and electrophysiological studies in mouse models have identified a neuropathic component of SCD pain; SCD patients and mice exhibit robust mechanical and cold hypersensitivity that is further exacerbated following a vaso-occlusive event. As a result, we tested the analgesic effects of gabapentin, one of the first line therapies for neuropathic pain, in male and female transgenic SCD mice. A single dose of gabapentin (30 mg/kg) alleviated steady state mechanical hypersensitivity in the hindpaw but had no effect on steady state cold hypersensitivity, deep muscle pain, or facial mechanical hypersensitivity. In a separate experiment, gabapentin was administered daily for 4 weeks to model neuropathic pain patient therapy. This chronic administration did not alleviate steady state mechanical hypersensitivity, cold hypersensitivity, or deep muscle pain in SCD mice. However, chronic gabapentin treatment did prevent hypoxia-induced exacerbation of mechanical hypersensitivity in SCD mice. Notably, a single dose of gabapentin administered shortly after hypoxia treatment alleviated ischemia-induced mechanical hypersensitivity to a greater extent than chronic gabapentin treatment. Finally, the effects of gabapentin on spontaneous pain-like behaviors and spontaneous neuronal activity were assessed using conditioned place preference and ex vivo skin nerve recordings respectively. Collectively, these data demonstrate that the drivers of acute vaso-occlusive crisis pain and chronic mechanical hypersensitivity may be caused by different factors, the former of which may be alleviated by gabapentin treatment.

Quantitative sensory testing in patients with sensitive skin

Quantitative sensory testing in patients with sensitive skin

Children and adolescents with sickle cell disease have worse cold and mechanical hypersensitivity during acute painful events.

Sickle cell disease (SCD) pain associates with cold temperature and touch. Patients and murine models with SCD have baseline thermal and mechanical pain. In SCD mice, the baseline hypersensitivity is exacerbated by experimental vaso-occlusive crises. We hypothesized that patients with SCD will similarly experience increased hypersensitivity to thermal and mechanical stimuli during acute painful events compared with baseline health. We conducted a prospective study of 24 patients with SCD aged 7 to 19 years. Patients underwent quantitative sensory testing to thermal (cold/heat) and mechanical stimuli on the thenar eminence of the nondominant hand (glabrous skin) and the lateral dorsum of the foot (hairy skin) during baseline health and within 48 hours of hospitalization for acute pain. Primary outcomes were changes in: (1) cold pain threshold (°C), (2) heat pain threshold (°C), and (3) mechanical pain threshold (g). Median age was 10.5 (interquartile range [IQR] 9-14.8) years, 67% were females, and 92% were on hydroxyurea. Patients with SCD had increased cold pain sensitivity in the hand during hospitalization compared with baseline (25.2°C [IQR 18.4-27.5°C] vs 21.3°C [IQR 4.9-26.2°C]; P = 0.011) and increased mechanical pain sensitivity in the foot during hospitalization (0.32 g [IQR 0.09-1.1 g] vs 1.7 g [IQR 0.4-8.3 g]; P = 0.003). There were no differences in heat pain sensitivity. The increased cold (P = 0.02) and mechanical (P = 0.0016) pain sensitivity during hospitalization persisted after adjusting for age, sex, hydroxyurea use, opioid consumption, and numeric pain score. Thus, cold and mechanical pain is significantly worse during an acute SCD painful event as compared to baseline health in patients with SCD.