Characteristics Of Neuropathic Pain Research Articles

Neuropathy and pain in Fabry disease

Fabry disease (FD) is a multiorgan lysosomal storage disorder caused by mutations in the alfa-galactosidase A (GLA ) gene. Pathogenic GLA mutations lead to impaired or even lost enzyme activity, which causes the accumulation of sphingolipids, e.g., globotriaosylceramide, in cells and tissues. The majority of FD patients experience triggerable pain, mainly acral and burning, which often begins in early childhood. While small fiber pathology is assumed to be the basis of FD pain, the underlying molecular mechanisms are not well understood. This review summarizes the clinical characteristics of neuropathy and neuropathic pain in FD, presents current treatment options, and gives an overview of the latest findings from experimental and human model systems on the pathomechanisms contributing to small fiber pathology and FD-associated pain.

Central Sensitization in Patients with Chronic Pain Secondary to Carpal Tunnel Syndrome and Determinants.

Central sensitization (CS) is commonly seen in chronic pain disorders, including neuropathic pain. However, there exist inconsistencies concerning the presence of CS in chronic pain secondary to carpal tunnel syndrome (CTS). CS and neuropathic pain manifestations in CTS remain not well established. Therefore, this study aims to investigate the CS and pain profiles in patients with CTS and to explore the potential determinants associated with CS. Patients with suspected CTS symptoms lasting 3 months or above and healthy controls were enrolled. History, physical examinations, and nerve conduction studies were employed to confirm the diagnosis and severity of median nerve dysfunction. The central sensitization inventory (CSI) was used to screen CS. Other outcomes included neuropathic pain, CTS-specific symptom severity and functions, emotion, and health-related quality of life. Between-group comparisons were conducted in terms of the CS presence. Logistic regression analysis was performed to identify determinants associated with CS. Over 60% of participants with CTS were found with clinical CS, significantly higher than that in the control group. More than 70% of the CTS participants were identified to have possible or very likely neuropathic pain components. In addition, one-fourth of CTS cases had depression or anxiety. Anxiety was associated with an increased risk of developing CS in CTS (adjusted OR=1.31, 95% CI 1.08-1.59), whereas higher self-perceived general health rating was negatively associated with the presence of CS (adjusted OR=0.92, 95% CI 0.88-0.97) in the multivariate adjusted regression model. CS is prevalent in patients with CTS. Predominant neuropathic pain characteristics were uncovered in CTS patients as well as comorbid psychological distress. Significant association was found between anxiety and CS presence. Self-perceived general health was inversely related to CS. Further research is warranted to explore the mechanisms of anxiety and central pain processing in painful entrapment neuropathy.

Investigational Pregabalin Effect on Sleep in Patients with Neuropathic Pain and Sleep Maintenance Disturbance: A Multicentric Study

Objective: Our goal is to research how Pregabalin affects sleep maintenance in a group of neuropathic pain patients. Method and Material: A cross-sectional study including a sample of 600 patients was carried out. Patients with a neuropathic pain diagnosis were selected from three hospitals in Gandhinagar. After a medical professional diagnosed the patients with neuropathic pain, they were given a detailed description of the study's approach and asked for their informed consent. Subjects who are open to participating in the study and meet the inclusion and exclusion requirements. The demographic baseline evaluation and PSQI score were completed during Visit-01. After Visit-01, patients began receiving Pregabalin. After approximately 30 days from the date of enrolment, the patient was being monitored. The PSQI score was evaluated 30 days later. The Independent Ethics Committee (IEC) approved the PSQI Questioner and Informed Consent form after reviewing them. SPSS was used to statistically analyze the data (p < 0.05). Results: To evaluate variations in the distribution of "sleep disturbances vs. Sleep maintenance" (PSQI), we looked at the PSQI by time point. By using two-tailed paired t-tests, PSQI were compared for baseline and intervention conditions. Pregabalin treatment pre- and post-treatment were shown to differ significantly. Discussion: Sleep disturbances are prevalent characteristics of neuropathic pain that are well-known and well-documented. Patients with Neuropathic Pain had statistically significant improvements in sleep maintenance in the current investigation. Conclusion: The data presented here show that Pregabalin improves sleep quality in patients being treated for neuropathic pain

Neuropathic Pain in Patients with Psoriatic Arthritis: A Bystander or a Gamechanger?

Objectives
 
 The relationship between clinical and laboratory parameters associated with the neuropathic pain presence in Psoriatic Arthritis is not well known and has not been adequately studied. Based on these assumptions, the aim of our study is to investigate how often neuropathic pain occurs in Psoriatic Arthritis patients and how much it is related to the clinical and laboratory parameters of the disease.
 
 Methods
 
 In the cross-sectional study, 45 Psoriatic Arthritis patients diagnosed according to The Classification Criteria for Psoriatics were included. In our study, Pain Detect Questionnaire (PDQ) was used to assess the neuropathic pain characteristics. Presence of enthesitis was determined by SPARCC to ensure objective measurements. Functional status was evaluated with the Health Assessment Questionnaire (HAQ). The Short Form-36 (SF-36) questionnaire was used to evaluate the quality of life.
 
 Results
 
 A total of 45 patients were included in the study. The mean duration of symptoms was 78.91 ± 95.8 months. There are 16 patients receiving Nsaid treatment, 28 patients receiving DMARD treatment, and 13 patients receiving biological therapy. Among the patients included in the study, 30 patients with neuropathic pain and 15 without neuropathic pain were found according to the Pain Detect questionnaire. A significant difference was observed between these two groups in the results of DAPSA, VAS movement, HAQ, morning stiffness, and SF-36 Body pain.
 
 Conclusion
 
 Our study has shown that neuropathic pain has a high prevalence in Psoriatic Arthritis patients. This association was observed to be related to functional limitation. Additionally, the DAPSA score was found to be significantly higher in patients with neuropathic pain due to pain sensation which suggests that it may be a factor reducing treatment success. It is conceivable that the recognition and treatment of neuropathic pain may increase the success of Psoriatic Arthritis treatment.

Effect of an intraoperative periradicular application of platelet-rich fibrin (PRF) on residual post-surgical neuropathic pain after disc herniation surgery: study protocol for NeuroPRF, a randomized controlled trial

BackgroundThe prevalence of post-surgical lumbar neuropathic radiculopathy is approximately 30%. Poor response to the recommended treatments for neuropathic pain, namely antidepressants and/or gabapentinoids, requires the development of new techniques to prevent chronic pain. One such well-tolerated technique is the administration of autologous plasma enriched in platelets and fibrin (PRF). This approach is largely used in regenerative medicine owing to the anti-inflammatory and analgesic properties of PRF. It could also be an interesting adjuvant to surgery, as it reduces neurogenic inflammation and promotes nerve recovery, thereby reducing the incidence of residual postoperative chronic pain. The aim of the present study is to evaluate the benefit of periradicular intraoperative application of PRF on the residual postsurgical neuropathic pain after disc herniation surgery.MethodsA randomized, prospective, interventional, controlled, single-blind study with evaluation by a blind outcome assessor will be performed in Strasbourg University Hospital. We will compare a control group undergoing conventional surgery to an experimental group undergoing surgery and periradicular administration of PRF (30 patients in each arm). The primary outcome is the intensity of postoperative neuropathic radicular pain, measured by a visual analog scale (VAS) at 6 months post-surgery. The secondary outcomes are the characteristics of neuropathic pain (NPSI), the quality of life (SF-12 and PGIC), the presence of anxiety/depression symptoms (HAD), and the consumption of analgesics. We will also carry out transcriptomic analysis of a panel of pro- and anti-inflammatory cytokines in blood samples, before surgery and at 6 months follow-up. These gene expression results will be correlated with clinical data, in particular, with the apparition of postoperative neuropathic pain.DiscussionThis study is the first randomized controlled trial to assess the efficacy of PRF in the prevention of neuropathic pain following surgery for herniated disc. This study addresses not only a clinical question but will also provide information on the physiopathological mechanisms of neuropathic pain.Trial registrationThis study is registered at ClinicalTrials.gov: NCT05196503, February 24, 2022.

Site matters: Central neuropathic pain characteristics and somatosensory findings after brain and spinal cord lesions.

It is unknown if different etiologies or lesion topographies influence central neuropathic pain (CNP) clinical manifestation. We explored the symptom-somatosensory profile relationships in CNP patients with different types of lesions to the central nervous system to gain insight into CNP mechanisms. We compared the CNP profile through pain descriptors, standardized bedside examination, and quantitative sensory test in two different etiologies with segregated lesion locations: the brain, central poststroke pain (CPSP, n=39), and the spinal cord central pain due to spinal cord injury (CPSCI, n=40) in neuromyelitis optica. Results are expressed as median (25th to 75th percentiles). CPSP presented higher evoked and paroxysmal pain scores compared to CPSCI (p < 0.001), and lower cold thermal limen (5.6°C [0.0-12.9]) compared to CPSCI (20.0°C [4.2-22.9]; p=0.004). CPSCI also had higher mechanical pain thresholds (784.5 mN [255.0-1078.0]) compared to CPSP (235.2mN [81.4-1078.0], p=0.006) and higher mechanical detection threshold compared to control areas (2.7 [1.5-6.2] vs. 1.0 [1.0-3.3], p=0.007). Evoked pain scores negatively correlated with mechanical pain thresholds (r=-0.38, p < 0.001) and wind-up ratio (r=-0.57, p < 0.001). CNP of different etiologies may present different pain descriptors and somatosensory profiles, which is likely due to injury site differences within the neuroaxis. This information may help better design phenotype mechanism correlations and impact trial designs for the main etiologies of CNP, namely stroke and spinal cord lesions. This study provides evidence that topography may influence pain symptoms and sensory profile. The findings suggest that CNP mechanisms might vary according to pain etiology or lesion topography, impacting future mechanism-based treatment choices.

Co-Morbid Depression in Neuropathic Pain Sufferers: Prevalence and Effect on Quality of Life

The treatment of neuropathic pain is notoriously challenging, and this is often attributed to the psychiatric comorbidity that is commonly misunderstood as being the primary cause of the patient's suffering. Our study aimed to determine the relationship between depressive symptoms and the characteristics of neuropathic pain (NP), on the one hand, and quality of life (QoL), on the other hand, in a group of individuals who sought treatment for neuropathic pain (NP) regardless of the etiology of their condition. NP is a type of pain that is caused by damage to the nerves in the body. Study Pace: Kulsoom International Hospital Islamabad Study Duration: 6months (Feb 2021 to July 2021) Methods: We conducted a study with 60 individuals who came in seeking advice for neuropathic pain. The study was a cross-sectional design. We evaluated these participants based on their levels of five different parameters: their levels of neuropathic pain, as measured by DN4, their levels of pain intensity, as measured by EVA, their levels of anxiety and depression, as measured by the HADS, and their levels of quality of life. Results: The participants' average age was 55.23 ± 20.67 years, the ratio of males to females was 0.54. The mean age of the people who took part in the study was 55.23 years. The three conditions that were seen most commonly as causes of neuropathic pain were postherpetic pain, carpal tunnel syndrome, and diabetic neuropathy. Depression affected the mental health of 64.9% of persons, while anxiety was a problem for 70.5% of individuals. The quality of life was significantly lower than expected given the average scores of 34.82 on the SF-12 physical subscale and 38.26 on the SF-12 mental subscale. On the BPI, the total mean score was 5.60, and the standard deviation was 1.77. Patients with high DN4 scores showed a significantly increased risk of becoming depressed (p = 0.024), compared to patients with lower DN4 values. This was demonstrated to be the case by the fact that there was a statistically significant positive association between the depression score and the level of pain (p = 0.001, r = 0.41). Patients who were diagnosed with depression were found to have a poor quality of life using both the SF-12 and the BPI. Conclusion: Given the impact that depression has on the components of neuropathic pain as well as quality of life, screening for this comorbidity ought to be a part of the baseline assessment for ND.

Effects of Capparis Spinosa extract on the neuropathic pain induced by chronic constriction injury in rats.

Neuropathic pain, a chronic pain condition, puts a considerable burden on its patients. However, different pathophysiological characteristics of neuropathic pain make the current treatment medications insufficient in controlling pain. Identifying treatment effects with Capparis Spinosa hydro-alcoholic extract in an animal model of neuropathic pain. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the components of C. Spinosa hydro-alcoholic extract. To establish a neuropathic pain model, adult male Wistar rats underwent chronic constriction injury (CCI) surgery in their left sciatic nerve. Male wistar rats were divided into four groups: CCI, Sham, CCI with C. Spinosa (100mg/kg), and CCI with C. Spinosa (200mg/kg). Rats were treated with a hydro-alcoholic extract from aerial parts of the C. Spinosa (orally, daily) starting from CCI induction until 14 days after. Behavioral tests (mechanical allodynia, cold allodynia, and thermal hyperalgesia) and biochemical tests (IL-1β, TNF-α, MDA, and total thiol) were taken from animals. The LC-MS analysis identified 22 compounds in C. Spinosa extract with the predominance of flavonoids. CCI produced a significant (P < 0.001) increase allodynia (mechanical and cold) and thermal hyperalgesia in comparison with sham group. Oral administration of C. Spinosa significantly (P < 0.05) ameliorated CCI-induced nociceptive pain compared with CCI group. Spinal cord specimens of CCI rats had significant (P < 0.05) elevated inflammation status (↑IL-1β, ↑TNF-α), and significant (P < 0.05) decreased antioxidative status (↑MDA, ↓total thiol) in comparison with the sham group. These changes were reversed following C. Spinosa treatment. C. Spinosa alleviates neuropathic pain by exhibiting antioxidative and anti-inflammatory effects. The responsible components for these effects are possibly the flavonoid compounds in C. Spinosa extract.

Nöropatik ağrı aksiyal spondiloartritte gözden kaçan bir semptom mu?

Purpose: Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatologic disease. Pain is the most common symptom affecting quality of life in axSpA patients. It has been showed that pain is not always correlated with inflammation in patients. The aim of our study was to investigate the frequency of neuropathic pain in axSpA patients and relationship between neuropathic pain and patient characteristics.&#x0D; Materials and Methods: Patients diagnosed as axSpA according to the Assessment of SpondyloArthritis International Society classification criteria, who presented in our outpatients clinics from January to March 2019 were included in this study. The neuropathic component of pain was evaluated with Douleur Neuropathique en 4 Questions (DN4) questionnaire. &#x0D; Results: Eighty seven axSpA patients were included in the study. Thirty of patients had neuropathic pain according to DN4 questionnaire (DN4&gt;4). Neuropathic pain was higher in active disease group depending on both of ASDAS-CRP and BASDAI. DN4 score of patients was found moderately correlated with ASDAS-CRP and BASDAI score. A weak positive correlation was found between patients education level and DN4 score. &#x0D; Conclusion: We showed that neuropathic pain could be seen in patients with axSpA and it could be correlated with disease activity. The studies have proven that neuropathic pain could lead to impaired quality of life and social &amp; emotional functions. Patients with neuropathic pain could not benefit from antiinflammatory treatments. Therefore evaluating of neuropathic pain is important in axSpA patients. Further studies on management of neuropathic pain in axSpA patients are needed.

Neurophysiopathological Aspects of Paclitaxel-induced Peripheral Neuropathy.

Chemotherapy is widely used as a primary treatment or adjuvant therapy for cancer. Anti-microtubule agents (such as paclitaxel and docetaxel) are used for treating many types of cancer, either alone or in combination. However, their use has negative consequences that restrict the treatment's ability to continue. The principal negative effect is the so-called chemotherapy-induced peripheral neuropathy (CIPN). CIPN is a complex ailment that depends on diversity in the mechanisms of action of the different chemotherapy drugs, which are not fully understood. In this paper, we review several neurophysiological and pathological characteristics, such as morphological changes, changes in ion channels, mitochondria and oxidative stress, cell death, changes in the immune response, and synaptic control, as well as the characteristics of neuropathic pain produced by paclitaxel.

An observational study of centrally facilitated pain in individuals with chronic low back pain.

Central pain facilitation can hinder recovery in people with chronic low back pain (CLBP). The objective of this observational study was to investigate whether indices of centrally facilitated pain are associated with pain outcomes in a hospital-based cohort of individuals with CLBP undertaking a pain management programme. Participants provided self-report and pain sensitivity data at baseline (n = 97) and again 3 months (n = 87) after a cognitive behavioural therapy-based group intervention including physiotherapy. Indices of centrally facilitated pain were pressure pain detection threshold, temporal summation and conditioned pain modulation at the forearm, Widespread Pain Index (WPI) classified using a body manikin, and a Central Mechanisms Trait (CMT) factor derived from 8 self-reported characteristics of anxiety, depression, neuropathic pain, fatigue, cognitive dysfunction, pain distribution, catastrophizing, and sleep. Pain severity was a composite factor derived from Numerical Rating Scales. Cross-sectional and longitudinal regression models were adjusted for age and sex. Baseline CMT and WPI each was associated with higher pain severity (CMT: r = 0.50, P < 0.001; WPI: r = 0.21, P = 0.04) at baseline and at 3 months (CMT: r = 0.38, P < 0.001; WPI: r = 0.24, P = 0.02). High baseline CMT remained significantly associated with pain at 3 months after additional adjustment for baseline pain (β = 2.45, P = 0.04, R 2 = 0.25, P < 0.0001). Quantitative sensory testing indices of pain hypersensitivity were not significantly associated with pain outcomes at baseline or at 3 months. Central mechanisms beyond those captured by quantitative sensory testing are associated with poor CLBP outcome and might be targets for improved therapy.

Clinical Experience of High Frequency and Low Frequency TENS in Treatment of Diabetic Neuropathic Pain in Russia.

Background: Transcutaneous electrical nerve stimulation (TENS) is presently one of the main methods of treatment for neuropathic pain in type II diabetes mellitus. The discussion about which TENS frequency is more effective in the treatment of neuropathic pain has been ongoing for many years. Despite this, the response of different aspects of neuropathic pain to various TENS modalities has not been sufficiently studied. Aim: To analyze changes in characteristics of neuropathic pain depending on the frequency of TENS. Materials and methods: Seventy-five Russian diabetic patients with painful distal axonal neuropathy were enrolled in the study. Patients were assigned to three groups: in the HF TENS group, 25 patients received standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin) + high-frequency TENS (HF); in the LF TENS group, 25 patients received standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin) + low-frequency TENS (LF); in the control group, 25 patients underwent just standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin). Pain intensity was calculated before and after treatment with visual analogue scale (VAS), McGill pain questionnaire (MPQ), Douleur Neuropathique 4 Questions (DN4) and Pain Drawing. Results: TENS increased the therapeutic effect of standard drug therapy, in the treatment of neuropathic pain, by 65.9% and prolonged its efficacy by 31% for up to 6 months after treatment. HF TENS had a more pronounced analgesic effect than LF TENS based on VAS (34.7%), sensory (57.6%) MPQ dimensions and DN4 (21%). Affective MPQ dimension with the use of LF TENS was lower than HF TENS by 34.7% immediately after treatment, by 47.3% after 2 months and by 34.8% after 6 months of the follow-up period. Conclusion: There are significant differences between HF and LF TENS based on pain assessment using various pain scales. This reflects the distinctive effects of different TENS modalities on different aspects of neuropathic pain.

Motor cortex inhibition as a fibromyalgia biomarker: a meta-analysis of transcranial magnetic stimulation studies

Fibromyalgia (FM) is a common and refractory chronic pain condition with multiple clinical phenotypes. The current diagnosis is based on a syndrome identification which can be subjective and lead to under or over-diagnosis. Therefore, there is a need for objective biomarkers for diagnosis, phenotyping, and prognosis (treatment response and follow-up) in fibromyalgia. Potential biomarkers are measures of cortical excitability indexed by transcranial magnetic stimulation (TMS). However, no systematic analysis of current evidence has been performed to assess the role of TMS metrics as a fibromyalgia biomarker. Therefore, this study aims to evaluate evidence on corticospinal and intracortical motor excitability in fibromyalgia subjects and to assess the prognostic role of TMS metrics as response biomarkers in FM. We conducted systematic searches on PubMed/Medline, Embase, and Cochrane Central databases for observational studies and randomized controlled trials on fibromyalgia subjects that used TMS as an assessment. Three reviewers independently selected and extracted the data. Then, a random-effects model meta-analysis was performed to compare fibromyalgia and healthy controls in observational studies. Also, to compare active versus sham treatments, in randomized controlled trials. Correlations between changes in TMS metrics and clinical improvement were explored. The quality and evidence certainty were assessed following standardized approaches. We included 15 studies (696 participants, 474 FM subjects). The main findings were: (1) fibromyalgia subjects present less intracortical inhibition (mean difference (MD) = −0.40, 95% confidence interval (CI) −0.69 to −0.11) and higher resting motor thresholds (MD = 6.90 μV, 95% CI 4.16 to 9.63 μV) when compared to controls; (2) interventions such as exercise, pregabalin, and non-invasive brain stimulation increased intracortical inhibition (MD = 0.19, 95% CI 0.10 to 0.29) and cortical silent period (MD = 14.92 ms, 95% CI 4.86 to 24.98 ms), when compared to placebo or sham stimulation; (3) changes on intracortical excitability are correlated with clinical improvements – higher inhibition moderately correlates with less pain, depression, and pain catastrophizing; lower facilitation moderately correlates with less fatigue. Measures of intracortical inhibition and facilitation indexed by TMS are potential diagnostic and treatment response biomarkers for fibromyalgia subjects. The disruption in the intracortical inhibitory system in fibromyalgia also provides additional evidence that fibromyalgia has some neurophysiological characteristics of neuropathic pain. Treatments inducing an engagement of sensorimotor systems (e.g., exercise, motor imagery, and non-invasive brain stimulation) could restore the cortical inhibitory tonus in FM and induce clinical improvement.

Identifying Discomplete Spinal Lesions: New Evidence from Pain-Autonomic Interaction in Spinal Cord Injury.

The clinical evaluation of spinal afferents is an important diagnostic and prognostic marker for neurological and functional recovery after spinal cord injury (SCI). Particularly important regarding neuropathic pain following SCI is the function of the spinothalamic tract (STT) conveying nociceptive and temperature information. Here, we investigated the added value of neurophysiological methods revealing discomplete STT lesions; that is, residual axonal sparing in clinically complete STT lesions. Specifically, clinical pinprick testing and thermal thresholds were compared with objective contact heat-evoked potentials (CHEPs) and a novel measure of pain-autonomic interaction employing heat-induced sympathetic skin responses (SSR). The test stimuli (i.e., contact heat, pinprick) were applied below the lesion level in 32 subjects with thoracic SCI while corresponding heat-evoked responses (i.e., CHEPs and SSR) were recorded above the lesion (i.e., scalp and hand, respectively). Readouts of STT function were related to neuropathic pain characteristics. In subjects with abolished pinprick sensation, measures of thermosensation (10%), CHEPs (33%), and SSR (48%) revealed residual STT function. Importantly, SSRs can be used as an objective readout and when abolished, no other proxy indicated residual STT function. No relationship was found between STT function readouts and spontaneous neuropathic pain intensity and extent. However, subjects with clinically preserved STT function presented more often with allodynia (54%) than subjects with discomplete (13%) or complete STT lesions (18%). In individuals with absent pinprick sensation, discomplete STT lesions can be revealed employing pain-autonomic measures. The improved sensitivity to discerning STT lesion completeness might support the investigation of its association with neuropathic pain following SCI.

Multifarious Targets and Recent Developments in the Therapeutics for the Management of Bone Cancer Pain.

Bone cancer pain (BCP) is a distinct pain state showing characteristics of both neuropathic and inflammatory pain. On average, almost 46% of cancer patients exhibit BCP with numbers flaring up to as high as 76% for terminally ill patients. Patients suffering from BCP experience a compromised quality of life, and the unavailability of effective therapeutics makes this a more devastating condition. In every individual cancer patient, the pain is driven by different mechanisms at different sites. The mechanisms behind the manifestation of BCP are very complex and poorly understood, which creates a substantial barrier to drug development. Nevertheless, some of the key mechanisms involved have been identified and are being explored further to develop targeted molecules. Developing a multitarget approach might be beneficial in this case as the underlying mechanism is not fixed and usually a number of these pathways are simultaneously dysregulated. In this review, we have discussed the role of recently identified novel modulators and mechanisms involved in the development of BCP. They include ion channels and receptors involved in sensing alteration of temperature and acidic microenvironment, immune system activation, sodium channels, endothelins, protease-activated receptors, neurotrophins, motor proteins mediated trafficking of glutamate receptor, and some bone-specific mechanisms. Apart from this, we have also discussed some of the novel approaches under preclinical and clinical development for the treatment of bone cancer pain.

Clinical and electrophysiological characteristics of neuropathic pain in leprosy patients: A prospective cross-sectional study.

Introduction Neuropathic pain is a common and disabling late complication of leprosy. We investigated the clinical and electrophysiological characteristics of neuropathic pain in leprosy patients by evaluating nerve conduction, sympathetic skin response (SSR) and A-waves. Methods Twenty one leprosy patients with neuropathic pain validated by the Douleur Neuropathique en 4 (DN4)Questionnaire were selected for study. Pain intensity was measured by the visual analog scale. Demographic and clinical data were collected for all patients. Clinical data included appraisal of the median, ulnar, radial, tibial and common peroneal nerves, assessment of the sympathetic skin response and conventional electrophysiological recordings. Results Among all electroneuromyographic presentations, multifocal mononeuropathy was still the most prevalent. Sensory loss was observed more frequently than motor deficits. As most patients presented advanced clinical forms of leprosy and were under treatment, this high mean was found and the ulnar nerve was most frequently affected. The sympathetic skin response was absent in 16 patients. Higher DN4 Questionnaire scores were observed in women and in those receiving corticosteroid therapy. These inferences are possible to be made, but our study's limitations don't allow us to be certain about it. The statistical significance found only permits us to evidence what we related on the textual part of the study. Limitations The small number of patients studied, the lack of sophisticated diagnostic methods for leprosy, as well as the difficulties in assessing nerve conduction were the main limitations of this study. Conclusion The neurophysiological and clinical findings in leprous neuropathy were modest despite the conspicuous neuropathic pain. Although electrophysiological studies are a vital tool to verify nerve damage, variations in the clinical presentation of leprosy neuropathic pain render the diagnosis challenging. Further studies are needed to describe the neurophysiological evolution of this disease.

Assessment of Neuropathic Pain in Ankylosing Spondylitis: Prevalence and Characteristics.

IntroductionPain in ankylosing spondylitis is currently considered an inflammatory pain (IP). However, it was found that some patients still had the sensation of pain even without inflammation. Our study was to investigate the prevalence and characteristics of neuropathic pain (NeP) in Chinese Han ankylosing spondylitis (AS) patients.MethodsThe study consisted of three parts. Firstly, we assessed the prevalence and clinical data of NeP in 182 AS patients. Secondly, we evaluated pain improvement after etanercept therapy in 63 patients. Finally, serum neurotransmitters were measured for 20 AS patients and ten healthy controls (HC).ResultsOut of 182 AS patients, our study showed that 14 patients (7.70%) had likely NeP and 55 (30.21%) had uncertain NeP. There were significant differences among the three groups with respect to nocturnal pain (NP), peripheral pain (PP), total back pain (TBP), BASDAI, ASDAS-CRP, HAD-A, HAD-D, and BASDAI-fatigue except fort CRP concentrations. Principal component analysis (PCA) of AS pain revealed that the weight of NeP was greater than PP in the first principal component (0.703 vs. 0.639). Structural equation modeling (SEM) revealed that NeP altered disease activity (β = 0.62, P < 0.001), which influenced psychological status (β = 0.42, P < 0.001). Of 63 patients who used etanercept for 3 months, significant improvement was found in NP, TBP, and PP (all P < 0.0001) but not in PDQ (10.60 ± 6.85 vs. 9.98 ± 6.40, P = 0.0671). Serum norepinephrine concentrations in patients with PDQ > 19 were higher than those in patients with PDQ ≤ 19 and HC.ConclusionsWe conclude that NeP contributes to pain in AS patients.

Neuropathic component of postoperative pain for predicting post-cesarean chronic pain at three months: a prospective observational study.

Recent investigations have showed that cesarean section (CS) might be a cause of chronic pain, with a consequent decrease in quality of life. Prospective observational study in a Spanish tertiary hospital. Main outcome measure was to assess early neuropathic characteristics of pain (DN2 score ≥3) one week after CS as a potential risk factor for post-cesarean section chronic pain (PCSCP) at three months. Secondary outcome was to identify other risk factors. Six hundred ten consecutive consenting patients undergoing CS were interviewed preoperatively, at discharge from recovery room and 24 hours postoperatively. Telephone follow-up interviews were conducted one week, three months and twelve months following surgery. We analyzed 597 consecutive patients. The incidence of PCSCP at three and twelve postoperative months were 6.2% and 1% respectively. Subjects with NRS score superior to five on movement one week after CS presented higher incidence of PCSCP (NRS superior to five: 19 [52.2%]; NRS equal or lower to five: 172 [30.9%]; P=0.009). On multivariate analysis neuropathic pain one week after CS was associated with a higher risk of PCSCP (AOR=1.63 [95% CI: 1.26-2.11; P<0.001]). Other identified risk factors for PCSCP were: uterine exteriorization during CS (AOR=3.89 [95% CI: 1.25-12.10; P=0.019]) and a lower gestational age (AOR=0.87 [95% CI: 0.78-0.96; P=0.008]). Incidence of PCSCP at three and twelve postoperative months was low, 6.2% and 1% respectively. Early neuropathic characteristics of pain after one week measured by neuropathic pain questionnaire, consisting of two questions (DN2)≥3/7 could be used to identify patients at risk for chronic post-surgical pain and develop preventive strategies.

The Evaluation of Pain with Nociceptive and Neuropathic Characteristics from Three Different Perspectives in Amyotrophic Lateral Sclerosis Patients: A Case Controlled Observational Study in Southwestern China.

Background Pain was considered a common and neglected symptom in amyotrophic lateral sclerosis (ALS) and had a substantial impact on the quality of life of ALS patients and their caregivers. However, pain in ALS was mainly evaluated from the perspective of nociceptive pain; only three studies referred to neuropathic pain in ALS, and there has been yet no study considering the neuropathic pain characteristics in ALS patients from China. Therefore, the purpose of our study was to determine characteristics of pain (nociceptive pain and neuropathic pain) by three different types of questionnaires. The correlation between pain and clinical parameters in ALS patients was also evaluated. Methods Patients were eligible if they fulfilled the criteria of probable and definitive ALS according to the revised El Escorial criteria. Healthy normal controls, matched to ALS patients by age and gender, were recruited. Pain was evaluated by numerical pain rating scale (NRS), Brief Pain Inventory (BPI), and Douleur Neuropathique-4 (DN4) in ALS patients and controls. Physical status of ALS patients was evaluated with ALS Functional Rating Scale-revised (ALSFRS-R). Results 65 patients with sporadic ALS and 100 healthy normal controls in Southwestern China were included. Pain in the preceding week was more frequently reported by patients with ALS (30, 46.2%) than controls (36, 36%) (p = 0.193). DN4 score⩾4 was found in three ALS patients and one control (p = 0.480). Ten ALS patients (33.3%) and twenty-eight controls (77.8%) (p < 0.001) received therapy for pain. ALS patients with a DN4 score ≥ 4 had a longer disease duration and a higher PSI and PII score than ALS cases reporting nociceptive pain (p = 0.041, 0.048, and 0.027, respectively). Pain mainly interfered with ALS patients' mood, enjoyment of life, and the Pain Interference Index (PII) score. Conclusions Our findings indicated that pain in our ALS cohorts was insufficiently treated and interfered with patients' mood and enjoyment of life. Most notably, we found that ALS patients with a DN4 score⩾4 may have a longer disease duration and a higher PSI and PII score than ALS patients reporting nociceptive pain, which has never been reported, strongly deserving further validation.

Evaluation and diagnosis of neuropathic pain

Background: Thorough evaluation and an accurate diagnosis of neuropathic pain are essential for effective treatment. The therapeutic approach and choice of medication for neuropathic pain are different from those for other kinds of nociceptive pain. Therefore, this study aimed to present the current evaluation and diagnostic methods for neuropathic pain.Current Concepts: Grading of the certainty of the presence of neuropathic pain according to the results of clinical history, neurological examination, and confirmatory tests improves the diagnosis of neuropathic pain. The Leeds Assessment of Neuropathic Symptoms and Signs, Neuropathic Pain Questionnaire, Douleur Neuropathique en 4 Questions, and PainDETECT are mainly used for neuropathic pain screening. During physical examination, sensory nerve function tests are more critical than other nervous system examination items, including the test of the sense of touch with a cotton swab and the sense of vibration with a tuning fork. In addition, pain sensation using pins and temperature sensation using cold metal are tested to check for nociceptive pathway abnormalities. Diagnostic tests include imaging tests, nerve conduction tests, and other neurophysiological tests, such as quantitative sensory function tests, autonomic nerve function tests, and blood tests.Discussion and Conclusion: To diagnose neuropathic pain, physicians should first determine whether patient symptoms match the characteristics of neuropathic pain. If there is a possibility of neuropathic pain, physicians should perform a neurological screening examination and a proper diagnostic test to identify the cause of pain.