A preliminary investigation into psychophysiological effects of threatening a perceptually embodied rubber hand in healthy human participants

Background and aims: Threatening a perceptually embodied rubber hand with noxious stimuli has been shown to generate levels of anxiety similar to that experienced when a real hand is threatened. The aim of this study was to investigate skin conductance response, self-reported anxiety and the incidence, type and location of sensations when a perceptually embodied rubber was exposed to threatening and non-threatening stimuli. Methods: A repeated measures cross-over design was used whereby 20 participants (>18 years, 14 females) received a threatening (syringe needle) and non-threatening (soft brush) stimulus to a perceptually embodied rubber hand. Perceptual embodiment was achieved using a soft brush to synchronously stroke the participant’s real hand (out of view) and a rubber hand (in view). Then the investigator approached the rubber hand with a syringe needle (threat) or soft brush (non-threat). Results: Repeated measures ANOVA found that approaching the perceptually embodied rubber hand with either stimulus produced statistically significant reductions in the rated intensity of response to the following questions (p<0.01): ‘How strongly does it feel like the rubber hand is yours?’; ‘How strongly does it feel like the rubber hand is part of your body?’; and ‘How strongly does it feel you can move the rubber hand?’. However, there were no statistically significant differences in scores between needle and brush stimuli. Repeated measures ANOVA on skin conductance response found statistically significant effects for experimental Events (baseline; stroking; perceptual embodiment; stimuli approaching rubber hand; stimuli touching rubber hand; p<0.001) but not for Condition (needle versus brush p=0.964) or experimental Event x Condition interaction (p=0.160). Ten of the 20 participants (50%) reported that they experienced a sensation arising from the rubber hand when the rubber hand was approached and touched by either the needle and/or brush but these sensations lacked precision in location, timing, and nature. Conclusion and Implications: Our preliminary findings suggest that the increase in arousal in response to stimuli entering the peripersonal space may not be selective for threat. There was tentative evidence that more intense sensations were experienced when a perceptually embodied rubber hand was approached by a threatening stimulus. Our findings provide initial insights and should serve as a catalyst for further research

The relationship between regional pain with or without neuropathic symptoms and chronic widespread pain.

This study was performed to test whether the risk of developing chronic widespread pain (CWP) in those with regional pain was augmented in those with symptoms of neuropathic pain (NP). Persons free of CWP completed the Douleur Neuropathique 4 (scores ≥3 indicating NP); demographics; Hospital Anxiety and Depression scale; Pittsburgh Sleep Quality Index; and pain medications. Participants were classified as having no pain, regional pain with no symptoms of NP (NP-), or regional pain with symptoms of NP (NP). At the 12-month follow-up, participants with CWP were identified. Logistic regression estimated the odds ratio, with 95% confidence intervals, of CWP in the NP- and NP groups compared with no pain, and NP compared with NP-. Partial population attributable risks estimated the proportion of CWP attributable to baseline NP- or NP exposure. One thousand one hundred sixty-two participants completed the baseline DN4 and provided pain data at follow-up: 523 (45.0%) had no baseline pain, 562 (48.4%) NP-, and 77 (6.6%) NP. One hundred fifty-three (13.2%) had CWP at 12 months: 19 (3.6%) no pain, 108 (19.2%) NP-, and 26 (33.8%) NP. NP- (2.9 [1.9-4.3]) and NP (2.1 [1.1-4.0]) predicted CWP after adjusting for demographics, Hospital Anxiety and Depression scale, Pittsburgh Sleep Quality Index, and medications. The partial population attributable risk was 41.3% (25.2-54.0) for NP- and 6.0% (0.1-11.6) for NP. The NP group were not more likely to develop CWP when compared directly with NP- (1.5 [0.8-2.8]). Neuropathic pain was relatively rare and predicted a small number of new-onset CWP cases. Using these estimates, treatments targeting NP would at best prevent 6% of CWP cases

Cancer-Related Neuropathic Pain.

Neuropathic pain in cancer is common and debilitating. It is important to differentiate neuropathic pain from other cancer-related pains as it is associated with worse pain outcomes and requires different treatment strategies. This review summarises recent updates to pain classification, aetiology, pain assessment and current recommendations for treatment in patients with cancer-related neuropathic pain

Characterising the Features of 381 Clinical Studies Evaluating Transcutaneous Electrical Nerve Stimulation (TENS) for Pain Relief: A Secondary Analysis of the Meta-TENS Study to Improve Future Research.

Background and Objectives: Characterising the features of methodologies, clinical attributes and intervention protocols, of studies is valuable to advise directions for research and practice. This article reports the findings of a secondary analysis of the features from studies screened as part of a large systematic review of TENS (the meta-TENS study). Materials and Methods: A descriptive analysis was performed on information associated with methodology, sample populations and intervention protocols from 381 randomised controlled trials (24,532 participants) evaluating TENS delivered at a strong comfortable intensity at the painful site in adults with pain, irrespective of diagnosis. Results: Studies were conducted in 43 countries commonly using parallel group design (n = 334) and one comparator group (n = 231). Mean ± standard deviation (SD) study sample size (64.05 ± 58.29 participants) and TENS group size (27.67 ± 21.90 participants) were small, with only 13 of 381 studies having 100 participants or more in the TENS group. Most TENS interventions were 'high frequency' (&gt;10 pps, n = 276) and using 100 Hz (109/353 reports that stated a pulse frequency value). Of 476 comparator groups, 54.2% were active treatments (i.e., analgesic medication(s), exercise, manual therapies and electrophysical agents). Of 202 placebo comparator groups, 155 used a TENS device that did not deliver currents. At least 216 of 383 study groups were able to access other treatments whilst receiving TENS. Only 136 out of 381 reports included a statement about adverse events. Conclusions: Clinical studies on TENS are dominated by small parallel group evaluations of high frequency TENS that are often contaminated by concurrent treatment(s). Study reports tended focus on physiological and clinical implications rather than the veracity of methodology and findings. Previously published criteria for designing and reporting TENS studies were neglected and this should be corrected in future research using insights gleaned from this analysis

Efficacy and safety of transcutaneous electrical nerve stimulation (TENS) for acute and chronic pain in adults: a systematic review and meta-analysis of 381 studies (the meta-TENS study).

OBJECTIVE: To investigate the efficacy and safety of transcutaneous electrical nerve stimulation (TENS) for relief of pain in adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Cochrane Central, Embase (and others) from inception to July 2019 and updated on 17 May 2020. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials (RCTs) comparing strong non-painful TENS at or close to the site of pain versus placebo or other treatments in adults with pain, irrespective of diagnosis. DATA EXTRACTION AND SYNTHESIS: Reviewers independently screened, extracted data and assessed risk of bias (RoB, Cochrane tool) and certainty of evidence (Grading and Recommendations, Assessment, Development and Evaluation). Mean pain intensity and proportions of participants achieving reductions of pain intensity (≥30% or >50%) during or immediately after TENS. Random effect models were used to calculate standardised mean differences (SMD) and risk ratios. Subgroup analyses were related to trial methodology and characteristics of pain. RESULTS: The review included 381 RCTs (24 532 participants). Pain intensity was lower during or immediately after TENS compared with placebo (91 RCTs, 92 samples, n=4841, SMD=-0·96 (95% CI -1·14 to -0·78), moderate-certainty evidence). Methodological (eg, RoB, sample size) and pain characteristics (eg, acute vs chronic, diagnosis) did not modify the effect. Pain intensity was lower during or immediately after TENS compared with pharmacological and non-pharmacological treatments used as part of standard of care (61 RCTs, 61 samples, n=3155, SMD = -0·72 (95% CI -0·95 to -0·50], low-certainty evidence). Levels of evidence were downgraded because of small-sized trials contributing to imprecision in magnitude estimates. Data were limited for other outcomes including adverse events which were poorly reported, generally mild and not different to comparators. CONCLUSION: There was moderate-certainty evidence that pain intensity is lower during or immediately after TENS compared with placebo and without serious adverse events. PROSPERO REGISTRATION NUMBER: CRD42019125054

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

Objective: 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. Databases and Data Treatment: 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). Results: 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. Conclusion: 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. Significance: 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

Characterization and Comparison of 2 Distinct Epidemic Community-Associated Methicillin-Resistant Staphylococcus aureus Clones of ST59 Lineage.

Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the β-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more α-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of α-toxin, and possibly the loss of a large portion of the β-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone