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.

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.

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.

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).

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.

No evidence of widespread mechanical pressure hyperalgesia after experimentally induced central sensitization through skin nociceptors.

Introduction: An increasing number of clinical studies involving a range of chronic pain conditions report widespread mechanical pressure pain hypersensitivity, which is commonly interpreted as resulting from central sensitization (CS). Secondary hyperalgesia (increased pinprick sensitivity surrounding the site of injury) is considered to be a manifestation of CS. However, it has not been rigorously tested whether CS induced by peripheral nociceptive input involves widespread mechanical pressure pain hypersensitivity.

Central sensitization and pain hypersensitivity: Some critical considerations.

Since its discovery, central sensitization has gained enormous popularity. It is widely used to explain pain hypersensitivity in a wide range of clinical pain conditions. However, at present there is no general consensus on the definition of central sensitization.

High frequency electrical stimulation induces a long-lasting enhancement of event-related potentials but does not change the perception elicited by intra-epidermal electrical stimuli delivered to the area of increased mechanical pinprick sensitivity.

High frequency electrical stimulation (HFS) of the skin induces increased pinprick sensitivity in the surrounding unconditioned skin. The aim of the present study was to investigate the contribution of A-fiber nociceptors to this increased pinprick sensitivity. For this we assessed if the perception and brain responses elicited by low-intensity intra-epidermal electrical stimulation (IES), a method preferentially activating Aδ-fiber nociceptors, are increased in the area of HFS-induced increased pinprick sensitivity.

Quickly responding C-fibre nociceptors contribute to heat hypersensitivity in the area of secondary hyperalgesia.

Key Points: A recent animal study showed that high frequency electrical stimulation (HFS) of C-fibres induces a gliogenic heterosynaptic long-term potentiation at the spinal cord that is hypothesized to mediate secondary hyperalgesia in humans. Here this hypothesis was tested by predominantly activating C-fibre nociceptors in the area of secondary mechanical hyperalgesia induced by HFS in humans. It is shown that heat perception elicited by stimuli predominantly activating C-fibre nociceptors is greater, as compared to the control site, after HFS in the area of secondary mechanical hyperalgesia.

Event-related brain potentials elicited by high-speed cooling of the skin: A robust and non-painful method to assess the spinothalamic system in humans.

Objective: To investigate whether cool-evoked potentials (CEP) elicited by brisk innocuous cooling of the skin could serve as an alternative to laser-evoked potentials (LEP), currently considered as the best available neurophysiological tool to assess the spinothalamic tract and diagnose neuropathic pain.

Methods: A novel device made of micro-Peltier elements and able to cool the skin at -300 °C/s was used to record CEPs elicited by stimulation of the hand dorsum in 40 healthy individuals, characterize the elicited responses, and assess their signal-to-noise ratio. Various stimulation surfaces (40 mm and 120 mm), cooling ramps (-200 °C/s and -133 °C/s) and temperature steps (20 °C, 15 °C, 10 °C, 5 °C) were tested to identify optimal stimulation conditions.

Phase-locked and non-phase-locked EEG responses to pinprick stimulation before and after experimentally-induced secondary hyperalgesia.

Objective: Pinprick-evoked brain potentials (PEPs) have been proposed as a technique to investigate secondary hyperalgesia and central sensitization in humans. However, the signal-to-noise (SNR) of PEPs is low. Here, using time-frequency analysis, we characterize the phase-locked and non-phase-locked EEG responses to pinprick stimulation, before and after secondary hyperalgesia.

Intense pain influences the cortical processing of visual stimuli projected onto the sensitized skin.

Sensitization is a form of implicit learning produced by the exposure to a harmful stimulus. In humans and other mammals, sensitization after skin injury increases the responsiveness of peripheral nociceptors and enhances the synaptic transmission of nociceptive input in the central nervous system. Here, we show that sensitization-related changes in the central nervous system are not restricted to nociceptive pathways and, instead, also affect other sensory modalities, especially if that modality conveys information relevant for the sensitized body part.