Pressure Stimuli Research Articles

Perceptual amplification following sustained attention: implications for hypervigilance.

It is known that attending to a cutaneous stimulus briefly increases its subjective intensity. The purpose of the present study was to determine whether an extended period of attention would produce a longer-lasting perceptual amplification. Eighty subjects were assigned alternately to experimental and control groups. Members of the two groups received identical series of tactile stimuli (near-threshold von Frey filaments applied to the forearm), but those in the experimental group carried out a two-interval forced-choice detection task that required attention to the filaments, while subjects in the control group attended instead to a video game. After this initial phase, all subjects gave magnitude estimates of the intensity of a wide range of von Frey filaments. The experimental group gave estimates 42% greater than those of the control group, both for filaments used in the initial phase, and others not presented previously; the perceptual amplification did not, however, transfer to a different type of pressure stimulus, a 5mm-diameter rod applied to the skin. The aftereffect of sustained attention lasted for at least 15min. This phenomenon, demonstrated in normal subjects, may have implications for the hypervigilance of some chronic pain patients, which is characterized by both heightened attention to pain and long-lasting perceptual amplification of noxious stimuli.

Effect of Genetic Polymorphisms on Pain Sensitivity in the Orofacial Region: A Systematic Review.

To systematically review the literature to assess whether genetic polymorphisms affect orofacial pain sensitivity in healthy individuals and in patients with chronic orofacial pain disorders. Electronic searches were conducted to identify observational studies and clinical trials investigating the association between genetic polymorphisms and orofacial pain sensitivity in healthy individuals and/or patients with chronic orofacial pain disorders. Searches were carried out in PubMed, Embase, and Scopus databases using Medical Subject Headings and free terms. Seven studies fulfilled the eligibility criteria: four analyzed healthy subjects, two included chronic orofacial pain patients, and one included samples of healthy subjects and patients with neuropathic pain. The results showed that genes associated with mechanical and thermal pain sensitivity were mostly related to opioid, catecholaminergic, inflammatory, and dopaminergic pathways. Genetic polymorphisms related to opioid, catecholaminergic, inflammatory, and dopaminergic pathways were associated with sensitivity to thermal and pressure stimuli in the orofacial region. Therefore, genetic factors should be taken into account for an accurate interpretation of orofacial pain sensitivity. These results will allow for a better understanding of the etiopathogenesis of chronic pain affecting the orofacial region, and consequently for finding new therapeutic targets.

M172 DELAYED PRESSURE URTICARIA MASQUERADING AS CHRONIC IDIOPATHIC URTICARIA

Delayed pressure urticaria (DPU) presents with cutaneous erythema and edema typically manifesting 4-6 hours after a sustained pressure stimulus. In approximately 40% of cases, DPU may co-exist with chronic idiopathic urticaria (CIU), thus masking symptoms. As DPU can severely impact quality of life and treatment is often refractory to antihistamines, recognizing the diagnosis is important to avoid treatment delays.

Aggregation-induced emission characteristics and distinct fluorescent responses to external pressure stimuli based on dumbbell D-π-A-π-D cyanostyrene derivatives

Abstract Two dumbbell cyanostyrene derivatives PBCAN and PBTAN have been designed and prepared. Quantum chemical calculations and optical spectra confirm that two compounds are D-π-A-π-D structures. Both of them show aggregation-induced emission (AIE) characteristic, giving high emission efficiency in solid state. Interestingly, two molecules exhibit distinct fluorescent response to external pressure stimuli. Upon the treatment of grinding, PBCAN exhibits unusual hypsochromic shift of the emission wavelength of 10 nm, while PBTAN shows bathochromic shift of 18 nm. We think that the former might be due to close molecular packing in the initial state, while the latter might be derived from the transformation of π-packing mode from H-aggregate to J-aggregate. The current result is valuable for exploiting structurally similar molecules with distinct MFC characteristics.

Lanthanide-Based Nanosensors: Refining Nanoparticle Responsiveness for Single Particle Imaging of Stimuli.

Lanthanide nanoparticles (LNPs) are promising sensors of chemical, mechanical, and temperature changes; they combine the narrow-spectral emission and long-lived excited states of individual lanthanide ions with the high spatial resolution and controlled energy transfer of nanocrystalline architectures. Despite considerable progress in optimizing LNP brightness and responsiveness for dynamic sensing, detection of stimuli with a spatial resolution approaching that of individual nanoparticles remains an outstanding challenge. Here, we highlight the existing capabilities and outstanding challenges of LNP sensors, en-route to nanometer-scale, single particle sensor resolution. First, we summarize LNP sensor read-outs, including changes in emission wavelength, lifetime, intensity, and spectral ratiometric values that arise from modified energy transfer networks within nanoparticles. Then, we describe the origins of LNP sensor imprecision, including sensitivity to competing conditions, interparticle heterogeneities, such as the concentration and distribution of dopant ions, and measurement noise. Motivated by these sources of signal variance, we describe synthesis characterization feedback loops to inform and improve sensor precision, and introduce noise-equivalent sensitivity as a figure of merit of LNP sensors. Finally, we project the magnitudes of chemical and pressure stimulus resolution achievable with single LNPs at nanoscale resolution. Our perspective provides a roadmap for translating ensemble LNP sensing capabilities to the single particle level, enabling nanometer-scale sensing in biology, medicine, and sustainability.

Increased somatosensory amplification is associated with decreased pressure pain thresholds at both trigeminal and extra-trigeminal locations in healthy individuals.

The diagnosis of temporomandibular disorders (TMD) is based on patient history and physical examination, and may require medical imaging. Masticatory muscle palpation is essential to make a diagnosis of TMD. However, the response of masticatory muscles to mechanical pressure stimuli depends on many physical and psychological factors. This study aimed at determining the impact of somatosensory amplification (SSA)-an estimate of somatic awareness and bodily hypervigilance-on pressure pain thresholds (PPTs) measured at both trigeminal and extra-trigeminal locations in healthy individuals. PPTs were measured at the right anterior temporalis and superficial masseter, and the thenar eminence of the right hand in one hundred healhty individuals (69F, 31M), divided in three groups based on their SSA scores: low (N=32), intermediate (N=34) and high (N=34). General linear models were used to test between-group differences in PPTs including sex as a covariate. The level of significance was set at P<.05. Individuals with high SSA had lower PPTs at the anterior temporalis than individuals with low (P=.006) and intermediate (P=.001) SSA. No significant between-group differences were found in PPTs measured at the masseter (P=.372). PPTs measured at the thenar eminence were significantly lower in the high than the low SSA group (P=.009). Females had lower PPTs at the masseter than males (P=.021) but not at other muscle locations (all P>.05). Increased somatosensory amplification is associated with decreased pressure pain thresholds at both trigeminal and extra-trigeminal locations in healthy individuals. SSA could be a potential confounder while diagnosing TMD and evaluating treatment outcomes.

Multisensory Sensitivity is Related to Deep-Tissue but Not Cutaneous Pain Sensitivity in Healthy Individuals.

PurposeSome individuals with chronic pain find daily life sensations (eg, noise, light, or touch) aversive. This amplification of multisensory sensations has been associated with centrally mediated plasticity; for example, greater multisensory sensitivity (MSS) occurs in patients with fibromyalgia than rheumatoid arthritis. However, whether MSS preferentially relates to pain measures which reflect central influences (eg, dynamic quantitative sensory testing (QST) or referred pain), or whether the MSS-pain relationship requires priming from chronic pain, is unknown. Thus, this cross-sectional study investigated the relationships between MSS assessed in a pain-free state and evoked pain sensitivity.MethodsExperimental intramuscular infusion pain and multiple static and dynamic QST were assessed in 465 healthy, pain-free adults: pain thresholds using pressure (PPTs) and heat (HPTs), temporal summation of pain (TSP) using pressure, heat or punctate stimuli, and conditioned pain modulation (CPM) using pressure or heat test stimuli. MSS was assessed using 7 items from Barsky’s Somatosensory Amplification Scale. Differences in pain and QST between sex-specific MSS quartiles were assessed, adjusting for multiple comparisons. All participants completed at least one intramuscular infusion condition, but not all were asked to complete each QST (n=166-465).ResultsBoth static and dynamic QST differed between highest and lowest MSS quartiles using pressure stimuli: lower PPTs (adjusted-p<0.01); increased pressure TSP (adjusted-p=0.02); lower pressure CPM (adjusted-p=0.01). However, none of the heat or punctate QST measures (HPTs, TSP, or CPM) differed between MSS quartiles (adjusted-p>0.05). Odds of experiencing TSP or referred pain was not greater, whereas CPM was 8-fold less likely, in those with highest MSS.ConclusionNormal variation in non-noxious MSS is related to both static and dynamic pain sensitivity, without sensitization associated with chronic pain, but is dependent on the QST stimulus. Thus, common influences on MSS and pain sensitivity may involve central mechanisms but are likely more complex than previously recognized.

Peripheral Occipital Nerve Decompression Surgery in Migraine Headache.

Background:Migraine headache in the occipital region is characterized by a recurrent pain of moderate to severe intensity. However, the diagnosis can be difficult because of the multitude of symptoms overlapping with similar disorders and a pathophysiology that is not well-understood. For this reason, the medical management is often complex and ineffective.Methods:A literature search according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted to evaluate the surgical treatment of occipital migraines. Inclusion criteria were: English language, diagnosis of migraine, occipital neuralgia, or tension headache in compliance with the classification of the International Headache Society, follow-up at minimum 3 months, and adult age. The treatment had to consist of peripheral occipital nerve surgery.Results:323 records were identified after duplicates were removed, 30 full text articles were assessed for eligibility, and 9 records were selected for inclusion. A total of 1046 patients were included in the review. General positive response after surgery (>50% reduction in occipital migraine headaches) ranged from 80.0% to 94.9%. However, many differences in the selection of patients, target of decompression surgery, and measurement outcome were described.Conclusion:Despite the decennial proven effectiveness and safeness of surgical therapy for chronic occipital migraine headaches, more significant proof is needed to definitively confirm its use as a standard therapy.

Contact Modulated Ionic Transfer Doping in All‐Solid‐State Organic Electrochemical Transistor for Ultra‐High Sensitive Tactile Perception at Low Operating Voltage

AbstractIonic‐electronic coupling across the entire volume of conjugated polymer films endows organic electrochemical transistors (OECTs) with high transconductance (gm) and low operating voltage. However, OECTs utilize liquid electrolytes, which limit their long‐term operation, reproducibility, and integration while solid electrolytes typically result in inefficient ion transport. Here, a solid polymer electrolyte is shown that can facilitate good electrochemical response in conjugated polymers and yield high OECT performance. This allows for the OECT‐based pressure sensors, modulated through a pressure sensitive ionic doping process. The pressure sensor exhibits the highest sensitivity ever measured (≈10 000 kPa−1) and excellent stability. Flexible sensor arrays achieve static capture of spatial pressure distribution and enable monitoring of dynamic pressure stimuli. The findings here demonstrate that all‐solid‐state OECTs are good candidates for providing rich tactile information, enabling applications for soft robotics, health monitoring, and human‐machine interfaces.

Pressure Stimuli Improve the Proliferation of Wharton's Jelly-Derived Mesenchymal Stem Cells under Hypoxic Culture Conditions.

Mesenchymal stem cells (MSCs) are safe, and they have good therapeutic efficacy through their paracrine action. However, long-term culture to produce sufficient MSCs for clinical use can result in side-effects, such as an inevitable senescence and the reduction of the therapeutic efficacy of the MSCs. In order to overcome this, the primary culture conditions of the MSCs can be modified to simulate the stem cells’ niche environment, resulting in accelerated proliferation, the achievement of the target production yield at earlier passages, and the improvement of the therapeutic efficacy. We exposed Wharton’s jelly-derived MSCs (WJ-MSCs) to pressure stimuli during the primary culture step. In order to evaluate the proliferation, stemness, and therapeutic efficacy of WJ-MSCs, image, genetic, and Western blot analyses were carried out. Compared with standard incubation culture conditions, the cell proliferation was significantly improved when the WJ-MSCs were exposed to pressure stimuli. However, the therapeutic efficacy (the promotion of cell proliferation and anti-apoptotic effects) and the stemness of the WJ-MSCs was maintained, regardless of the culture conditions. Exposure to pressure stimuli is a simple and efficient way to improve WJ-MSC proliferation without causing changes in stemness and therapeutic efficacy. In this way, clinical-grade WJ-MSCs can be produced rapidly and used for therapeutic applications.

Artificial Somatosensors: Feedback Receptors for Electronic Skins

The human skin is the largest sensory organ, made up of complex sensors that detect noxious stimuli to rapidly send warning signals to the central nervous system to initiate a motor response. It is complex to mimic key skin features using existing tactile sensors, and there exists no somatosensor that responds to real stimuli of pressure, temperature, and touch. Herein, three critical skin receptors created by realizing integrated electronic systems that mimic the feedback response of somatosensors are experimentally demonstrated. Fully functional Pacinian corpuscles, thermoreceptors, and nociceptors are realized using a combination of stretchable pressure sensors, phase‐change oxide thin films, and threshold‐based resistive switching (memristor) memory elements. The ability to detect and respond to pressure, temperature, and pain stimuli above a threshold with real‐life performance characteristics is demonstrated with explanation of underlying mechanisms. The ability to design and realize artificial skin receptors enables replacement of affected human skin regions, augment skin sensitivity for agile applications in defense and sports, and drive advancements in intelligent robotics.

CENTRAL SENSITIZATION OF PAIN IN PHYSIOTHERAPY

Nowadays, there are three main pain descriptors: nociceptive pain, neuropathic pain, and nociplastic pain. The last one is the newest expression defining pain as ‘Pain that arises from altered nociception, despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain’ (International Association for the Study of Pain). The implementation of modern pain neuroscience in practice is said to be the most important for musculoskeletal physical therapists around the world. One of the examples of the nociplastic pain mechanism can be myofascial trigger points that are connected with central sensitization (one of the subtypes of nociplastic pain). Central sensitization (CS) is defined as an amplification of neural signaling within the central nervous system that elicits pain hypersensitivity and ongoing neuronal excitation which outlasts the initial nociceptor input. Features typical of that state are abnormally low peripheral thresholds for pain from pressure, temperature, electrical, and other stimuli and it has been proposed that trigger points may function as peripheral mediators of CS.

Flexible 3D Architectured Piezo/Thermoelectric Bimodal Tactile Sensor Array for E‐Skin Application

AbstractElectronic skin (e‐skin) functions as human–machines interaction interfaces, holding great promise in future personal health monitoring and endowing robots with capability of sense of touch. Despite recent exciting progress in e‐skin research, accurate discrimination of various tactile inputs remains a great challenge yet. A 3D processing technique is demonstrated here combining laser fabrication and screen printing to construct vertically architectured pressure/temperature bimodal active sensor employing all organic functional materials, i.e., piezoelectric poly(vinylidene fluoride‐co‐trifluoroethylene) and thermoelectric polyaniline‐based composites. The sensor transforms pressure and temperature stimuli into two independent electrical signals without interference, exhibiting high temperature sensing sensitivity (109.4 µV K−1) with rapid response time (0.37 s) and superior pressure sensing sensitivity over a wide range (100 Pa to 20 kPa). Finite element analyses further explain the thermal harvesting performance of the sensor. Applications of sensor as e‐skin in various temperature/stress perception scenarios and its stability are demonstrated. Further, a 4 × 4 pixel bimodal tactile sensor array is integrated for the first time, presenting accurate spatial distribution mapping of pressure/temperature signals simultaneously without interference, and functions without external power supply due to its intrinsic working principle. This study thus moves a step toward multifunctional flexible electronics for e‐skin applications.

Weavable and stretchable piezoresistive carbon nanotubes-embedded nanofiber sensing yarns for highly sensitive and multimodal wearable textile sensor

Developing multimodal wearable textile sensors to simulate the complex human skin characteristics is central for healthcare, electronic skins, artificial intelligence and biomedical electronic applications. In this paper, stretchable piezoresistive carbon nanotubes-embedded nanofiber sensing yarns are successfully produced and mechanically robust enough to be woven to a wearable textile sensor that can detect and differentiate the multiple mechanical stimuli of pressure, stretching and bending. The smart nanofiber sensing yarn is obtained by wrapping piezoresistive elastic nanofibers onto a stretchable fiber-shaped core electrode with a facile electrospinning technique. The delicate hierarchical structure of this textile sensor ranges from the 1D macroscopic yarns to the submicron elastic nanofibers and internal nanoscale CNT percolation networks. This type of sensor offers a relatively larger contact area, multiple contact sites and larger deformation space for multimodal sensing various mechanical stimuli with improved sensitivity and broad sensing range. The textile-based sensor can be conformally attached to complex surfaces or integrated into a textile, demonstrating an excellent capability of continuous transient detection and differentiation of dynamic human movements. Moreover, a textile sensing platform is successfully integrated for spatially mapping the pressure and strain distribution, which makes it a promising candidate for electronic textiles and wearable devices.

TRP Channels Role in Pain Associated With Neurodegenerative Diseases.

Transient receptor potential (TRP) are cation channels expressed in both non-excitable and excitable cells from diverse tissues, including heart, lung, and brain. The TRP channel family includes 28 isoforms activated by physical and chemical stimuli, such as temperature, pH, osmotic pressure, and noxious stimuli. Recently, it has been shown that TRP channels are also directly or indirectly activated by reactive oxygen species. Oxidative stress plays an essential role in neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, and TRP channels are involved in the progression of those diseases by mechanisms involving changes in the crosstalk between Ca2+ regulation, oxidative stress, and production of inflammatory mediators. TRP channels involved in nociception include members of the TRPV, TRPM, TRPA, and TRPC subfamilies that transduce physical and chemical noxious stimuli. It has also been reported that pain is a complex issue in patients with Alzheimer’s and Parkinson’s diseases, and adequate management of pain in those conditions is still in discussion. TRPV1 has a role in neuroinflammation, a critical mechanism involved in neurodegeneration. Therefore, some studies have considered TRPV1 as a target for both pain treatment and neurodegenerative disorders. Thus, this review aimed to describe the TRP-dependent mechanism that can mediate pain sensation in neurodegenerative diseases and the therapeutic approach available to palliate pain and neurodegenerative symptoms throughout the regulation of these channels.

Osmotic water permeability of aquaporin-1 under radial tensile and compressive stimuli

With the rapid development of biological technology and membrane synthesis, water industries have inclined towards biomimetic membranes for water purification and desalination. Aquaporin (AQP) embedded synthetic membranes seem to be promising due to the AQP's high selectivity and permeability, however, the effect of inherent membranous residual stress on protein structure and water permeation has been rarely studied yet and remains unclear. Here, we studied water permeability through the tetrameric human AQP1, embedded in a POPC lipid bilayer, under lateral mechanical stimuli using all-atom molecular dynamics simulations. Four different systems were studied where different stimuli were applied to the simulation cell. By counting the permeation events, we found that radially stretching protein though opens up and widens the pore in the planar direction; it reduced the final permeability compared to control. The hydrostatic pressure stimulus system possesses the highest permeability coefficient followed by the protein compressing system. By screening the water occupancy and pore-lining residues in different systems, we found that stretching the protein increased the dynamics of the pore-lining residues which interrupts the single-file line of water molecules in the pore, hence reducing the likelihood of water molecules to pass the pore. We also observed that the constriction site is located where the two pore-lining residues of ASN76 and ILE 60 meet. Our result provides a benchmark for designing a more efficient membrane desalination system for the treatment of water worldwide.

Flexible PZT-Integrated, Bilateral Sensors via Transfer-Free Laser Lift-Off for Multimodal Measurements.

Fabrication of functional devices that require a high-temperature annealing process on a thin, temperature-sensitive substrate is a long-standing, crucial issue in flexible electronics. Herein, we propose a transfer-free laser lift-off method to directly fabricate lead zirconate titanate (PZT) piezoelectric sensors that commonly undergo a high-temperature annealing (∼650 °C) on ubiquitous flexible substrates, including polyimide (∼300 °C), polyethylene terephthalate (∼120 °C), and polydimethylsiloxane (∼150 °C). The method includes the steps of fabricating sensors, encapsulating a flexible substrate, and peeling off the device by melting the sacrificial PZT layer at the interface with a sapphire glass. The appropriate fluence of laser energy has been figured out to avoid inadequate stripping or damage of the device. In addition, a process window for reliable stripping of the device has been established among the laser fluence and the thickness of the sacrificial layer and the supporting substrate. Furthermore, the capability of the newly proposed technique has been verified and expanded by successfully integrating several sensors that need skillful low-temperature heating treatment on top of a flexible supporting substrate accordingly before stripping. Finally, a PZT-integrated, bilateral multimodal sensor on a PI substrate has been fabricated, and the device demonstrates excellent performance and stability toward perceiving distributed dynamic pressure and temperature stimuli, revealing its high potential for the fabrication of high-performance devices for multimodal sensing applications.

Pain Processing in Older Adults and Its Association with Prefrontal Characteristics.

Aging is known to affect nociceptive processing, e.g., the ability to inhibit pain. This study aims to investigate whether pain responses in older individuals are associated with prefrontal characteristics, namely (i) executive functioning performance and (ii) structural brain variations in the prefrontal cortex. Heat and pressure stimuli were applied to assess pressure pain sensitivity and endogenous pain inhibition in 46 healthy older individuals. Executive functioning performance was assessed in three domains (i.e., cognitive inhibition, shifting, and updating) and structural brain variations were assessed in both gray and white matter. Overall pain responses were significantly associated with the executive functioning domains cognitive inhibition and shifting. However, no specific type of pain response showed an especially strong association. Endogenous pain inhibition specifically showed a significant association with gray matter volume in the prefrontal cortex and with variations in white matter structure of tracts connecting the prefrontal cortex with the periaqueductal gray. Hierarchical regression analyses showed that these variations in the prefrontal cortex can explain variance in pain inhibition beyond what can be explained by executive functioning. This might indicate that known deficits in pain inhibition in older individuals are associated with structural variations in prefrontal areas.

Modality-specific facilitation of noninjurious sharp mechanical pain by topical capsaicin.

We had previously shown that a "blunt blade" stimulator can mimic the noninjurious strain phase of incisional pain, but not its sustained duration. Here, we tested whether acute sensitization of the skin with topical capsaicin can add the sustained phase to this noninvasive surrogate model of intraoperative pain. Altogether, 110 healthy volunteers (55 male and 55 female; 26 ± 5 years) participated in several experiments using the "blunt blade" (0.25 × 4 mm) on normal skin (n = 36) and on skin pretreated by a high-concentration capsaicin patch (8%, Qutenza; n = 36). These data were compared with an experimental incision (n = 40) using quantitative and qualitative pain ratings by numerical rating scale and SES Pain Perception Scale descriptors. Capsaicin sensitization increased blade-induced pain magnitude and duration significantly (both P < 0.05), but it failed to fully match the sustained duration of incisional pain. In normal skin, the SES pattern of pain qualities elicited by the blade matched incision in pain magnitude and pattern of pain descriptors. In capsaicin-treated skin, the blade acquired a significant facilitation only of the perceived heat pain component (P < 0.001), but not of mechanical pain components. Thus, capsaicin morphed the descriptor pattern of the blade to become more capsaicin-like, which is probably explained best by peripheral sensitization of the TRPV1 receptor. Quantitative sensory testing in capsaicin-sensitized skin revealed hyperalgesia to heat and pressure stimuli, and loss of cold and cold pain sensitivity. These findings support our hypothesis that the blade models the early tissue-strain-related mechanical pain phase of surgical incisions.

The predictive value of quantitative sensory testing: a systematic review on chronic postoperative pain and the analgesic effect of pharmacological therapies in patients with chronic pain.

Studies have suggested that quantitative sensory testing (QST) might hold a predictive value for the development of chronic postoperative pain and the response to pharmacological interventions. This review systematically summarizes the current evidence on the predictive value of QST for chronic postoperative pain and the effect of pharmacological interventions. The main outcome measures were posttreatment pain intensity, pain relief, presence of moderate-to-severe postoperative pain, responders of 30% and 50% pain relief, or validated questionnaires on pain and disability. A systematic search of MEDLINE and EMBASE yielded 25 studies on surgical interventions and 11 on pharmacological interventions. Seventeen surgical and 11 pharmacological studies reported an association between preoperative or pretreatment QST and chronic postoperative pain or analgesic effect. The most commonly assessed QST modalities were pressure stimuli (17 studies), temporal summation of pain (TSP, 14 studies), and conditioned pain modulation (CPM, 16 studies). Of those, the dynamic QST parameters TSP (50%) and CPM (44%) were most frequently associated with chronic postoperative pain and analgesic effects. A large heterogeneity in methods for assessing TSP (n = 4) and CPM (n = 7) was found. Overall, most studies demonstrated low-to-moderate levels of risk of bias in study design, attrition, prognostic factors, outcome, and statistical analyses. This systematic review demonstrates that TSP and CPM show the most consistent predictive values for chronic postoperative pain and analgesic effect, but the heterogeneous methodologies reduce the generalizability and hence call for methodological guidelines.