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. High-frequency stimulation, traditionally delivered with non-charge-compensated square-wave pulses, may induce a cumulative depolarization of primary afferents and/or changes in pH at the electrode-tissue interface due to the accumulation of a net residue charge after each pulse. Both could contribute to the development of the increased pinprick sensitivity in a frequency-dependent fashion. We found no significant difference in the increase in pinprick sensitivity between HFS delivered with charge-compensated and non-charge-compensated pulses, indicating that the possible contribution of charge accumulation when non-charge-compensated pulses are used is negligible. In a second experiment, we assessed the effect of different frequencies of conditioning stimulation (5, 20, 42, and 100 Hz) using charge-compensated pulses on the development of increased pinprick sensitivity. The maximal increase in pinprick sensitivity was observed at intermediate frequencies of stimulation (20 and 42 Hz). It is hypothesized that the stronger increase in pinprick sensitivity at intermediate frequencies may be related to the stronger release of substance P and/or neurokinin-1 receptor activation expressed at lamina I neurons after C-fiber stimulation. NEW & NOTEWORTHY Burstlike electrical conditioning stimulation applied to human skin induces an increase in pinprick sensitivity in the surrounding unconditioned skin (a phenomenon referred to as secondary hyperalgesia). Here we show that the development of the increase in pinprick sensitivity is dependent on the frequency of the burstlike electrical conditioning stimulation.

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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. We developed an experimental study to investigate the effect of a manipulation of threat on experimentally-induced secondary hyperalgesia in 26 healthy human adults (16 identifying as female; 10 as male). We induced secondary hyperalgesia at both forearms using high-frequency electrical stimulation. Prior to the induction, we used a previously successful method to manipulate threat of tissue damage at one forearm (threat site). The effect of the threat manipulation was determined by comparing participant-rated anxiety, perceived threat, and pain during the experimental induction of secondary hyperalgesia, between the threat and control sites. We hypothesized that the threat site would show greater secondary hyperalgesia (primary outcome) and greater surface area (secondary outcome) of induced secondary hyperalgesia than the control site. Despite a thorough piloting procedure to test the threat manipulation, our data showed no main effect of site on pain, anxiety, or threat ratings during high-frequency electrical stimulation. In the light of no difference in threat between sites, the primary and secondary hypotheses cannot be tested. We discuss reasons why we were unable to replicate the efficacy of this established threat manipulation in our sample, including: (1) competition between threats, (2) generalization of learned threat value, (3) safety cues, (4) trust, and requirements for participant safety, (5) sampling bias, (6) sample-specific habituation to threat, and (7) implausibility of (sham) skin examination and report. Better strategies to manipulate threat are required for further research on the mechanisms by which threat influences pain.

According to limited-capacity theories, the processing of nociceptive stimuli may be reduced when less attentional resources are available, which may diminish the development of secondary hypersensitivity, i.e. the increased sensitivity to mechanical pinprick stimuli applied in the uninjured area. In this study, we used Low Frequency Stimulation (LFS) to examine the contributions of cognitive load, its modulation by sex, and sympathetic arousal to the development of secondary mechanical hypersensitivity. Eighty-four healthy participants were randomized into a low and a high cognitive load group. Before, during, and after LFS, participants executed a low or a high cognitive demanding task. Meanwhile, we recorded Steady-State Evoked Potentials (SSEPs) evoked by LFS as a proxy for attentional capture by LFS, and skin conductance level (SCL) for sympathetic arousal. After the task, participants reported task difficulty and pain-related fear. The perceived intensity and unpleasantness of mechanical pinprick stimuli was assessed before and 20 minutes after LFS. Although the cognitive load manipulation was successful, we did not find significant group or sex differences in perceived intensity and unpleasantness of mechanical pinprick stimuli and SSEPs power. Notwithstanding a lack of group differences in SCL, we observed a negative correlation between SCL before LFS and perceived intensity and unpleasantness of mechanical pinprick stimuli, whereas pain-related fear was positively correlated with perceived intensity and unpleasantness of mechanical pinprick stimuli. These results do not support the hypotheses that cognitive load and sex modulate hypersensitivity, but show associations with pain-related fear and non-pain-related sympathetic arousal.

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. Risk of bias was assessed with the SIGN case‐control study checklist. Findings were structured around dynamic quantitative sensory tests and their localization. Where possible, we performed meta‐analysis with a random inverse variance model to compare patients with TMDm and healthy controls. Statistical heterogeneity was estimated with Chi² test and inconsistency index, I². Results We extracted data from 23 studies comprising 1284 adults with chronic TMDm and 2791 healthy controls. Risk of bias was assessed as high for 20 studies. Mechanical temporal summation, the most studied phenomenon (14 studies), is increased in the upper limb of patients with TMDm (SMD = 0.43; 95% CI: .11 to .75; p = .009) but not in the jaw area (p = .09) or in the cervical area (p = .29). Very little evidence for altered thermal temporal summation (five studies), conditioned pain modulation (seven studies), exercise‐induced hypoalgesia (two studies), placebo analgesia (two studies), stress‐induced hypoalgesia (one study) and offset analgesia (one study) was found. Discussion A major limitation of this review was the risk of bias of included studies. Future studies would benefit from following methodological guidelines and consideration of confounding factors.