Central inhibition of pain is augmented in women with self-injurious behavior

Individuals who engage in nonsuicidal self-injury (NSSI) have demonstrated higher pain thresholds and tolerance compared with individuals without NSSI. The objective of the study was to assess which aspects of the pain regulatory system that account for this augmented pain perception. In a cross-sectional design, 81 women, aged 18-35 (mean [SD] age, 23.4 [3.9]), were included (41 with NSSI and 40 healthy controls). A quantitative sensory testing protocol, including heat pain thresholds, heat pain tolerance, pressure pain thresholds, conditioned pain modulation (assessing central down-regulation of pain), and temporal summation (assessing facilitation of pain signals) was used. Thermal pain stimuli were assessed during fMRI scanning and NSSI behaviors and clinical symptoms were self-assessed. NSSI participants demonstrated higher pain thresholds during heat and pressure pain compared to controls. During conditioned pain modulation, NSSI participants showed a more effective central down-regulation of pain for NSSI participants. Temporal summation did not differ between the groups. There were no correlations between pain outcomes and NSSI behaviors or clinical characteristics. The fMRI analyses revealed increased activity in the primary and secondary somatosensory cortex in NSSI participants, compared to healthy controls, which are brain regions implicated in sensory aspects of pain processing. The findings suggest segregated inhibitory mechanisms for pain and emotion in NSSI, as pain insensitivity was linked to enhanced inhibitory control of pain in spite of significant impairments in emotion regulation. This may represent an endophenotype associated with a greater risk for developing self-injurious behavior.

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Exploring the pain in patellofemoral pain: A systematic review and meta-analysis examining signs of central sensitization

Journal of Athletic Training ◽

10.4085/1062-6050-0190.20 ◽

2020 ◽

Author(s):

Kemery J. Sigmund ◽

Marie K. Hoeger Bement ◽

Jennifer E. Earl-Boehm

Keyword(s):

Systematic Review ◽

Central Sensitization ◽

Temporal Summation ◽

Meta Analysis ◽

Pain Modulation ◽

Conditioned Pain Modulation ◽

Pain Thresholds ◽

Pressure Pain ◽

Pressure Pain Thresholds ◽

Pain Mapping

Objective: Patellofemoral pain has high recurrence rates and minimal long-term treatment success. Central sensitization refers to dysfunctional pain modulation that occurs when nociceptive neurons become hyper responsive. Research in this area in PFP has been increasingly productive in the past decade. The aim of this review is to determine whether evidence supports manifestations of central sensitization in individuals with PFP. Data sources: MeSH terms for quantitative sensory testing (QST) pressure pain thresholds, conditioned pain modulation, temporal summation, sensitization, hyperalgesia, and anterior knee pain or PFP were searched in PubMed, SportDiscus, CINAHL, Academic Search Complete, and Ebscohost. Study Selection: Peer reviewed studies written in English, published between 2005–2020 which investigated QST and/or pain mapping in a sample with PFP were included in this review. Data Extraction: The initial search yielded 140 articles. After duplicates were removed, 78 article abstracts were reviewed. Full-text review of 21 studies occurred, with 11 studies included in the meta-analysis and eight studies included in the systematic review. Data Synthesis: A random-effects meta-analysis was conducted for four QST variables (local pressure pain thresholds, remote pressure pain thresholds, conditioned pain modulation, temporal summation). Strong evidence supports lower local and remote pressure pain thresholds, impaired conditioned pain modulation, and facilitated temporal summation in individuals with PFP compared to pain-free individuals. Conflicting evidence is presented for heat and cold pain thresholds. Pain mapping demonstrated expanding pain patterns associated with long PFP symptom duration. Conclusions: Signs of central sensitization are present in individuals with PFP, indicating altered pain modulation. PFP etiological and treatment models should reflect the current body of evidence regarding central sensitization. Signs of central sensitization should be monitored clinically and treatments with central effects should be considered as part of a multi-modal plan of care. Registration Number: This review is registered with Prospero (CRD42019127548) Registration URL: https://www.crd.york.ac.uk/PROSPERO Key Points:

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The Effect of Conditioned Pain Modulation on Tonic Heat Pain Assessed Using Participant-Controlled Temperature

Pain Medicine ◽

10.1093/pm/pnaa041 ◽

2020 ◽

Vol 21 (11) ◽

pp. 2839-2849

Author(s):

Laura Sirucek ◽

Catherine Ruth Jutzeler ◽

Jan Rosner ◽

Petra Schweinhardt ◽

Armin Curt ◽

...

Keyword(s):

Test Stimulus ◽

Temporal Summation ◽

Pressure Pain Threshold ◽

Conditioning Stimulus ◽

Pain Modulation ◽

Conditioned Pain Modulation ◽

Heat Pain ◽

Pressure Pain ◽

Withdrawal Reflex ◽

Pressure Pain Thresholds

Abstract Objective Descending pain modulation can be experimentally assessed by way of testing conditioned pain modulation. The application of tonic heat as a test stimulus in such paradigms offers the possibility of observing dynamic pain responses, such as adaptation and temporal summation of pain. Here we investigated conditioned pain modulation effects on tonic heat employing participant-controlled temperature, an alternative tonic heat pain assessment. Changes in pain perception are thereby represented by temperature adjustments performed by the participant, uncoupling this approach from direct pain ratings. Participant-controlled temperature has emerged as a reliable and sex-independent measure of tonic heat. Methods Thirty healthy subjects underwent a sequential conditioned pain modulation paradigm, in which a cold water bath was applied as the conditioning stimulus and tonic heat as a test stimulus. Subjects were instructed to change the temperature of the thermode in response to variations in perception to tonic heat in order to maintain their initial rating over a two-minute period. Two additional test stimuli (i.e., lower limb noxious withdrawal reflex and pressure pain threshold) were included as positive controls for conditioned pain modulation effects. Results Participant-controlled temperature revealed conditioned pain modulation effects on temporal summation of pain (P = 0.01). Increased noxious withdrawal reflex thresholds (P = 0.004) and pressure pain thresholds (P < 0.001) in response to conditioning also confirmed inhibitory conditioned pain modulation effects. Conclusions The measured interaction between conditioned pain modulation and temporal summation of pain supports the participant-controlled temperature approach as a promising method to explore dynamic inhibitory and facilitatory pain processes previously undetected by rating-based approaches.

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Pain thresholds and suprathreshold pain after sleep restriction in migraine – A blinded crossover study

Cephalalgia ◽

10.1177/03331024211056565 ◽

2021 ◽

pp. 033310242110565

Author(s):

Jan Petter Neverdahl ◽

Martin Uglem ◽

Dagfinn Matre ◽

Johannes Orvin Hansen ◽

Morten Engstrøm ◽

...

Keyword(s):

Crossover Study ◽

Pain Sensitivity ◽

Sleep Restriction ◽

Heat Pain ◽

Healthy Controls ◽

Pain Thresholds ◽

Pressure Pain ◽

Disturbed Sleep ◽

Pressure Pain Thresholds ◽

Lower Pain

Objective There is an unexplained association between disturbed sleep and migraine. In this blinded crossover study, we investigate if experimental sleep restriction has a different effect on pain thresholds and suprathreshold pain in interictal migraineurs and controls. Methods Forearm heat pain thresholds and tolerance thresholds, and trapezius pressure pain thresholds and suprathreshold pain were measured in 39 interictal migraineurs and 31 healthy controls after two consecutive nights of partial sleep restriction and after habitual sleep. Results The effect of sleep restriction was not significantly different between interictal migraineurs and controls in the primary analyses. Pressure pain thresholds tended to be lower (i.e., increased pain sensitivity) after sleep restriction in interictal migraineurs compared to controls with a 48-hour preictal-interictal cut-off (p = 0.061). We found decreased pain thresholds after sleep restriction in two of seven migraine subgroup comparisons: heat pain thresholds decreased in migraineurs with lower pain intensity during attacks (p = 0.005) and pressure pain thresholds decreased in migraineurs with higher severity of photophobia during attacks (p = 0.031). Heat pain thresholds tended to decrease after sleep restriction in sleep-related migraine (p = 0.060). Sleep restriction did not affect suprathreshold pain measurements in either group. Conclusion This study could not provide strong evidence for an increased effect of sleep restriction on pain sensitivity in migraineurs compared to healthy controls. There might be a slightly increased effect of sleep restriction in migraineurs, detectable using large samples or more pronounced in certain migraine subgroups.

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A pilot study investigating whether quantitative sensory testing alters after treatment in patients with fibromyalgia

British Journal of Pain ◽

10.1177/2049463718776336 ◽

2018 ◽

Vol 12 (4) ◽

pp. 250-256 ◽

Cited By ~ 6

Author(s):

Theresa Wodehouse ◽

Kavita Poply ◽

Shankar Ramaswamy ◽

Saowarat Snidvongs ◽

Julius Bourke ◽

...

Keyword(s):

Pilot Study ◽

Quantitative Sensory Testing ◽

Fibromyalgia Impact Questionnaire ◽

Pain Modulation ◽

Conditioned Pain Modulation ◽

Sensory Testing ◽

Central Sensitisation ◽

Pain Thresholds ◽

Pressure Pain ◽

Pressure Pain Thresholds

Background: Fibromyalgia is a chronic musculoskeletal pain condition that is often associated with sleep disturbances and fatigue. The pathophysiology of fibromyalgia is not understood, but indirect evidence suggests a central dysfunction of the nociceptive modulating system. The aim of this study was to evaluate whether quantitative sensory testing detects a change in pain thresholds in fibromyalgia patient receiving pregabalin treatment. Methods: A total of 25 patients were recruited for the study and received routine pregabalin, but only 14 patients completed the treatment. Assessment of pressure pain thresholds and changes in conditioned pain modulation using ischaemic pain as a conditioning stimulus were measured at baseline and every 4 weeks for 12 weeks. Fibromyalgia impact questionnaire, PainDETECT and SF-12 were also completed. Results: Patients with fibromyalgia demonstrated a less-efficient conditioned pain modulation at baseline. An efficient conditioned pain modulation was observed at 1 month and this was maintained until the final visit. Pressure pain thresholds (PPTs) showed a significant improvement from baseline. Patients also reported a similar magnitude of improvements in PainDETECT, fibromyalgia impact questionnaire (FIQ) and its impact on daily life and change in outcome for SF-12. Conclusion: This pilot study reports an increase in PPTs and improved conditioned pain modulation response after commencing pregabalin, which was maintained at 12 weeks, and this was supported by positive pain scores. Pregabalin is a licenced treatment for fibromyalgia in Europe, and its response to central sensitisation, particularly ‘dynamic responses’, has not been reported. We conclude that pregabalin has the potential to reduce peripheral and central sensitisation in patients with fibromyalgia, as measured using quantitative sensory testing.

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Test–Retest Instability of Temporal Summation and Conditioned Pain Modulation Measures in Older Adults

Pain Medicine ◽

10.1093/pm/pnaa288 ◽

2020 ◽

Vol 21 (11) ◽

pp. 2863-2876

Author(s):

Kelly Marie Naugle ◽

Thomas Ohlman ◽

Brandon Wind ◽

Leah Miller

Keyword(s):

Older Adults ◽

Temporal Summation ◽

Temporal Stability ◽

Pain Modulation ◽

Self Report ◽

Conditioned Pain Modulation ◽

Heat Pain ◽

Younger Adults ◽

Healthy Older Adults ◽

Pressure Pain Thresholds

Abstract Objective The temporal stability (test–retest reliability) of temporal summation of pain (TS) and conditioned pain modulation (CPM) has yet to be established in healthy older adults. The purpose of this study was to compare the temporal stability of TS and CPM in healthy older and younger adults and to investigate factors that might influence TS and CPM stability. Methods In a test–retest study, 40 healthy older adults and 30 healthy younger adults completed two sessions of quantitative sensory testing within a two-week period that included TS of heat pain, TS of mechanical pain, and CPM with pressure pain thresholds and suprathreshold heat pain as test stimuli and a cold water immersion as a conditioning stimulus. Participants also completed self-report measures of situational catastrophizing, anxiety, clinical pain, and physical activity. Absolute and relative stability were examined for each variable. Bivariate correlations examined the associations of age, clinical, behavioral, and psychological variables with the intra-individual stability of TS and CPM. Results The results revealed moderate to excellent stability for the TS measures and poor to moderate stability for CPM. The results also revealed significant age differences for two of the TS measures and CPM, with younger adults having greater stability compared with older adults. Additionally, the magnitude and stability of psychological factors were correlated with stability of TS. Conclusions These findings suggest that TS and CPM may be more reliable in younger compared with older adults. Furthermore, psychological states may be an important factor influencing the stability of TS in healthy adults.

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Modulation of central sensitisation by detoxification in MOH: Results of a 12-month detoxification study

Cephalalgia ◽

10.1177/0333102412475235 ◽

2013 ◽

Vol 33 (7) ◽

pp. 444-453 ◽

Cited By ~ 26

Author(s):

Signe B Munksgaard ◽

Lars Bendtsen ◽

Rigmor H Jensen

Keyword(s):

Temporal Summation ◽

Pain Perception ◽

Threshold Pressure ◽

Healthy Controls ◽

Central Sensitisation ◽

Pain Thresholds ◽

Pressure Pain ◽

Pain Scores ◽

Pressure Pain Thresholds

Background Human and animal models suggest that central sensitisation plays a role in medication-overuse headache (MOH). We aimed to study pain perception in MOH patients before and a year after withdrawal. Methods We examined pain perception in 35 MOH patients before and two, six and 12 months after detoxification. For baseline comparison, we tested 40 healthy controls. We measured cephalic and extra-cephalic pressure-pain thresholds and supra-threshold pressure-pain scores and extra-cephalic pain thresholds, supra-threshold pain scores and temporal summation for electrical stimulation. Results Of the 35 patients, 21 patients completed the entire study and remained cured of MOH. Statistically significant differences between patients and healthy controls were found in cephalic pressure-pain thresholds (137.3 kPa vs. 170 kPa, p < 0.05), extra-cephalic pressure pain thresholds (213.3 vs. 274.3 kPa, p < 0.05), in cephalic supra-threshold pressure-pain scores measured on a 100 mm visual analogue scale (61 vs. 27 mm, p < 0.05) and extra-cephalic supra-threshold pain scores for electrical stimulation (19.0 vs. 10.0 mm, p < 0.05). Cephalic supra-threshold pain scores decreased statistically significantly from 50.3 mm at baseline to 28.0 mm at the 12-month follow-up. In contrast to controls, temporal summation was not found in MOH patients before withdrawal, but after detoxification temporal summation normalised. Conclusion The central nervous system is sensitised in patients with MOH. For the first time we demonstrate that the pain perception continues to normalise up to a year after detoxification. This emphasises the importance of detoxification and follow-up to prevent relapse.

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An Exploratory Study of Endogenous Pain Modulatory Function in Patients Following Mild Traumatic Brain Injury

Pain Medicine ◽

10.1093/pm/pnz058 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2198-2207 ◽

Cited By ~ 2

Author(s):

Christopher Carey ◽

Jonathan Saxe ◽

Fletcher A White ◽

Kelly M Naugle

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Exploratory Study ◽

Pain Modulation ◽

Conditioned Pain Modulation ◽

Pain Thresholds ◽

Pressure Pain Thresholds ◽

Post Traumatic ◽

Headache Pain ◽

Pain Inhibition

AbstractBackground. Recent animal research suggests that mild traumatic brain injury (mTBI) facilitates abnormal endogenous modulation of pain, potentially underlying the increased risk for persistent headaches following injury. However, no human studies have directly assessed the functioning of endogenous facilitory and inhibitory systems in the early stages after an mTBI. Objective. The purpose of this exploratory study was to examine trigeminal sensitization and endogenous pain inhibitory capacity in mTBI patients in the acute stage of injury compared with matched controls. We also examined whether post-traumatic headache pain intensity within the mTBI sample was related to sensitization and pain inhibitory capacity. Methods. Twenty-four mTBI patients recruited from emergency departments and 21 age-, race-, and sex-matched controls completed one experimental session. During this session, participants completed quantitative sensory tests measuring trigeminal sensitization (pressure pain thresholds and temporal summation of pain in the head) and endogenous pain inhibition (conditioned pain modulation). Participants also completed validated questionnaires measuring headache pain, depression, anxiety, and pain catastrophizing. Results. The results revealed that the mTBI group exhibited significantly decreased pressure pain thresholds of the head and decreased pain inhibition on the conditioned pain modulation test compared with the control group. Furthermore, correlational analysis showed that the measures of trigeminal sensitization and depression were significantly associated with headache pain intensity within the mTBI group. Conclusions. In conclusion, mTBI patients may be at risk for maladaptive changes to the functioning of endogenous pain modulatory systems following head injury that could increase risk for post-traumatic headaches.

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Stretch Reflex and Pressure Pain Thresholds in Chronic Tension-Type Headache Patients and Healthy Controls

Cephalalgia ◽

10.1111/j.1468-2982.2008.01772.x ◽

2009 ◽

Vol 29 (5) ◽

pp. 556-565 ◽

Cited By ~ 10

Author(s):

A Peddireddy ◽

K Wang ◽

P Svensson ◽

L Arendt-Nielsen

Keyword(s):

Stretch Reflex ◽

Tension Type Headache ◽

Healthy Controls ◽

Pain Thresholds ◽

Pressure Pain ◽

Chronic Tension Type Headache ◽

Control Subjects ◽

Pressure Pain Thresholds ◽

Type Headache ◽

Masseter Muscles

To compare the jaw-stretch reflex and pressure pain thresholds (PPT) in chronic tension-type headache (CTTH) patients and healthy controls, 30 patients (15 male and 15 female) and 30 age- and sex-matched healthy subjects were investigated. Stretch reflexes were recorded in the temporalis and masseter muscles and PPT was determined in the anterior temporalis, splenius capitis and masseter muscles. The results showed that the amplitude of the stretch reflex in CTTH patients was higher compared with control subjects ( P < 0.045), and higher in women compared with men in the right and left anterior temporalis muscles ( P < 0.009). There were no differences in the PPT value between CTTH and control subjects ( P > 0.509), whereas women showed significantly lower PPT measurements ( P < 0.046). The results demonstrated a facilitation of the stretch reflex pathways in CTTH patients that is unrelated to measures of pericranial sensitivity.

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