Preoperative susceptibility to developing secondary hyperalgesia is associated with post-thoracotomy pain at 2 months.

Background: Identifying the subset of patients at risk for developing persistent pain after surgery is clinically important as they could benefit from targeted prevention measures. In this prospective study, we investigated if the preoperative assessment of the individual susceptibility to developing experimentally induced secondary hyperalgesia is associated with post-thoracotomy pain at 2 months.

Methods: Forty-one patients scheduled to undergo a posterolateral thoracotomy were recruited before surgery and followed prospectively for 2 months.

Assessing signs of central sensitization: A critical review of physiological measures in experimentally induced secondary hyperalgesia.

Background And Objectives: Central sensitization (CS) is believed to play a role in many chronic pain conditions. Direct non-invasive recording from single nociceptive neurons is not feasible in humans, complicating CS establishment. This review discusses how secondary hyperalgesia (SHA), considered a manifestation of CS, affects physiological measures in healthy individuals and if these measures could indicate CS.

Studying the Effect of Expectations on High-Frequency Electrical Stimulation-Induced Pain and Pinprick Hypersensitivity.

Negative expectations can increase pain, but can they promote the development of central sensitization? This study used an inert treatment and verbal suggestions to induce expectations of increased high-frequency electrical stimulation (HFS)-induced pain and assessed their effects on pain ratings during HFS and HFS-induced pinprick hypersensitivity. Fifty healthy volunteers were randomly allocated to either a control group (N = 25) or a nocebo group (N = 25). Participants in both groups received a patch containing water on the right forearm.

Is chronic pain caused by central sensitization? A review and critical point of view.

Chronic pain causes disability and loss of health worldwide. Yet, a mechanistic explanation for it is still missing. Frequently, neural phenomena, and among them, Central Sensitization (CS), is presented as causing chronic pain.

Reconceptualizing sensitization in pain: back to basics.

Fillingim RB. Redefining sensitization could be a sensitive issue. PAIN Rep 2024;9:e1126.

Pinprick-induced gamma-band oscillations are not a useful electrophysiological marker of pinprick hypersensitivity in humans.

Objective: This study aimed to investigate scalp gamma-band oscillations (GBOs) induced by mechanical stimuli activating skin nociceptors before and after the induction of mechanical hypersensitivity using high-frequency electrical stimulation (HFS) of the skin.

Methods: In twenty healthy volunteers, we recorded the electroencephalogram during robot-controlled mechanical pinprick stimulation (512 mN) applied at the right ventral forearm before and after HFS.

Results: HFS induced a significant increase in mechanical pinprick sensitivity, but this increased pinprick sensitivity was, at the group level, not accompanied by a significant increase in GBOs.

The effect of high versus low cognitive load on the development of nociceptive hypersensitivity: The roles of sympathetic arousal, sex and pain-related fear.

Background: According to limited-capacity theories of attention, less attentional resources remain available when engaging in a high- versus a low-demanding cognitive task. This may reduce the perceived intensity and the evoked cortical responses of concomitant nociceptive stimuli. Whether and how the competition for limited attentional resources between a cognitive task and pain impacts the development of long-lasting hypersensitivity is unclear.

The Effect of Observing High or Low Pain on the Development of Central Sensitization.

It is unknown whether watching other people in high pain increases mechanical hypersensitivity induced by pain. We applied high-frequency electrical stimulation (HFS) on the skin of healthy volunteers to induce pinprick mechanical hypersensitivity. Before HFS participants were randomly allocated to 2 groups: in the low pain group, which was the control condition, they watched a model expressing and reporting lower pain scores, in the high pain group the model expressed and reported higher scores.

The influence of a manipulation of threat on experimentally-induced secondary hyperalgesia.

Pain is thought to be influenced by the threat value of the particular context in which it occurs. However, the mechanisms by which a threat achieves this influence on pain are unclear. Here, we explore how threat influences experimentally-induced secondary hyperalgesia, which is thought to be a manifestation of central sensitization.

Multichannel transcranial direct current stimulation over the left dorsolateral prefrontal cortex may modulate the induction of secondary hyperalgesia, a double-blinded cross-over study in healthy volunteers.

Background: Central sensitization is thought to play a critical role in the development of chronic pain, and secondary mechanical hyperalgesia is considered one of its hall-mark features. Consequently, interventions capable of modulating its development could have important therapeutic value. Non-invasive neuromodulation of the left dorsolateral prefrontal cortex (DLPFC) has shown potential to reduce pain, both in healthy volunteers and in patients.

Evidence for alterations to dynamic quantitative sensory tests in patients with chronic temporomandibular myalgia: A systematic review of observational studies with meta-analysis.

Background: Conflicting results exist between somatosensory profiles of patients with temporomandibular myalgia (TMDm). The objective of this review was to examine whether adults with TMDm show altered responses to dynamic quantitative sensory tests compared with healthy controls.

Methods: We searched five electronic databases for studies, excluding those without suitable controls or where TMDm was associated with confounding non-musculoskeletal disorders.

High-frequency electrical stimulation of cutaneous nociceptors differentially affects pain perception elicited by homotopic and heterotopic electrical stimuli.

Animal studies have shown that high-frequency electrical stimulation (HFS) of peripheral C-fiber nociceptors induces both homosynaptic and heterosynaptic long-term potentiation (LTP) within spinal nociceptive pathways. In humans, when HFS is applied onto the skin to activate nociceptors, single electrical stimuli are perceived more intense at the HFS site compared with a control site, a finding that was interpreted as a perceptual correlate of homosynaptic LTP. The present study aimed to investigate if after HFS the pain elicited by electrical stimuli delivered at the skin next to the HFS site is perceived as more intense compared with the pain at a control site (contralateral arm).

Stuck in the Middle With You: Why a Broad-Brush Approach to Defining Central Sensitization Does Not Help Clinicians and Patients.

Central sensitization is (1) increasingly interpreted as central nervous system hyperexcitability that accounts for a general increase in sensitivity, and (2) used to explain a variety of pain and nonpain symptoms. In this commentary, we argue that such a broad interpretation might not be clinically useful because it fails to distinguish one patient from another based on pathophysiological mechanisms and does not facilitate tailored treatment. We recommend that clinicians use a person-centered approach when assessing and managing patients, considering the different interacting processes/mechanisms that can contribute to a patient's clinical presentation.

Perceptual correlates of homosynaptic long-term potentiation in human nociceptive pathways: a replication study.

Animal studies have shown that high-frequency stimulation (HFS) of peripheral C-fibres induces long-term potentiation (LTP) within spinal nociceptive pathways. The aim of this replication study was to assess if a perceptual correlate of LTP can be observed in humans. In 20 healthy volunteers, we applied HFS to the left or right volar forearm.

Insular responses to transient painful and non-painful thermal and mechanical spinothalamic stimuli recorded using intracerebral EEG.

Brief thermo-nociceptive stimuli elicit low-frequency phase-locked local field potentials (LFPs) and high-frequency gamma-band oscillations (GBOs) in the human insula. Although neither of these responses constitute a direct correlate of pain perception, previous findings suggest that insular GBOs may be strongly related to the activation of the spinothalamic system and/or to the processing of thermal information. To disentangle these different features of the stimulation, we compared the insular responses to brief painful thermonociceptive stimuli, non-painful cool stimuli, mechano-nociceptive stimuli, and innocuous vibrotactile stimuli, recorded using intracerebral electroencephalograpic activity in 7 epileptic patients (9 depth electrodes, 58 insular contacts).

Central sensitization of nociceptive pathways demonstrated by robot-controlled pinprick-evoked brain potentials.

Objective: The aim of this study was to assess the effect of central sensitization, induced by high frequency electrical stimulation of the skin (HFS), on pinprick-evoked brain potentials (PEPs) using robot-controlled mechanical pinprick stimulation and a stimulus evaluation task.

Methods: In 16 healthy volunteers HFS was applied to the right volar forearm. Robot- controlled pinprick stimuli (64 mN) were applied before and 20 minutes after HFS to the skin surrounding the area onto which HFS was applied.

Within- and between-session reliability of secondary hyperalgesia induced by electrical high-frequency stimulation.

Background: An increasing number of studies are focusing on secondary hyperalgesia to better understand central sensitization, as this phenomenon may play an important role in persistent pain. Recent studies have shown that, compared to the classical high-frequency stimulation protocol (HFS) at 100 Hz, a protocol using 42 Hz stimulation induces a more intense and a larger area of secondary hyperalgesia (SH).

Objectives: The aim of this study was to investigate the within- and between-session reliability of SH induced by this optimized HFS protocol.

A highly cognitive demanding working memory task may prevent the development of nociceptive hypersensitivity.

Whether, how, and which cognitive factors modulate the development of secondary hypersensitivity/hyperalgesia after central sensitization is not fully understood. Here, we tested, in 3 subsequent experiments, whether being engaged in non-pain-related cognitive demanding tasks: (1) lessens the amount of hypersensitivity developed after an experimental procedure sensitizing nociceptive pathways; and (2) modulates cortical responses to somatosensory stimuli (measured by electroencephalography, EEG). In the first experiment, we validated a novel model in humans using low-frequency stimulation of the skin and demonstrated that it was able to successfully induce hypersensitivity to mechanical pinprick stimuli in the area surrounding the sensitized site.

The focus of spatial attention during the induction of central sensitization can modulate the subsequent development of secondary hyperalgesia.

Intense or sustained activation of peripheral nociceptors can induce central sensitization. This enhanced responsiveness to nociceptive input of the central nervous system primarily manifests as an increased sensitivity to painful mechanical pinprick stimuli extending beyond the site of injury (secondary mechanical hyperalgesia) and is thought to be a key mechanism in the development of chronic pain, such as persistent post-operative pain. It is increasingly recognized that emotional and cognitive factors can strongly influence the pain experience.

Burst-like conditioning electrical stimulation is more efficacious than continuous stimulation for inducing secondary hyperalgesia in humans.

The aim of the present study was to compare the efficacy of burst-like conditioning electrical stimulation vs. continuous stimulation of cutaneous nociceptors for inducing increased pinprick sensitivity in the surrounding unstimulated skin (a phenomenon referred to as secondary hyperalgesia). In a first experiment ( = 30), we compared the increase in mechanical pinprick sensitivity induced by 50-Hz burst-like stimulation ( = 15) vs.

Heterosynaptic facilitation of mechanical nociceptive input is dependent on the frequency of conditioning stimulation.

High-frequency burstlike electrical conditioning stimulation (HFS) applied to human skin induces an increase in mechanical pinprick sensitivity of the surrounding unconditioned skin (a phenomenon known as secondary hyperalgesia). The present study assessed the effect of frequency of conditioning stimulation on the development of this increased pinprick sensitivity in humans. In a first experiment, we compared the increase in pinprick sensitivity induced by HFS, using monophasic non-charge-compensated pulses and biphasic charge-compensated pulses.