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(1) Background: Dysregulation in serotonergic and noradrenergic systems may be implicated in the neurobiophysiological mechanisms underlying pain-related cognitive impairment in chronic whiplash-associated disorders (CWAD). This study aimed to unravel the role of serotonergic and noradrenergic descending pathways in cognitive functioning at rest and in response to exercise in people with CWAD. (2) Methods: 25 people with CWAD were included in this double-blind, randomized, controlled crossover study. Endogenous descending serotonergic and noradrenergic inhibitory mechanisms were modulated by using a single dose of a selective serotonin reuptake inhibitor (Citalopram) or a selective norepinephrine reuptake inhibitor (Atomoxetine). Cognitive performance was studied at rest and in response to exercise (1) without medication intake; (2) after intake of Citalopram; and (3) after intake of Atomoxetine. (3) Results: After Atomoxetine intake, selective attention improved compared with the no medication day (p < 0.05). In contrast, a single dose of Citalopram had no significant effect on cognitive functioning at rest. When performing pairwise comparisons, improvements in selective attention were found after exercise for the no medication condition (p < 0.05). In contrast, after intake of Citalopram or Atomoxetine, selective and sustained attention worsened after exercise. (4) Conclusions: A single dose of Atomoxetine improved selective attention only in one Stroop condition, and a single dose of Citalopram had no effect on cognitive functioning at rest in people with CWAD. Only without medication intake did selective attention improve in response to exercise, whereas both centrally acting medications worsened cognitive performance in response to a submaximal aerobic exercise bout in people with CWAD.

Background: Whiplash injuries typically occur from a motor vehicle collision and lead to chronic whiplash-associated disorders (CWAD) in 20% to 50% of cases. Changes in neurotransmission, metabolism, and networks seem to play a role in the pathogenic mechanism of CWAD. Objectives: To further elucidate the functional brain alterations, a neurophysiological study was performed to investigate the somatosensory processing of CWAD patients by comparing the event-related potentials (ERPs) resulting from electrical nociceptive stimulation between patients suffering from CWAD and healthy controls (HC). Study Design: Case-control study. Setting: University Hospital in Ghent. Methods: In this case-control study (CWAD patients/HC: 50/50), ankle and wrist electrical pain thresholds (EPT), and amplitude and latency of the event-related potentials (ERPs) resulting from 20 electrical stimuli were investigated. Correlations between the ERP characteristics, EPT, self-reported pain, disability, pain catastrophizing, and self-reported symptoms of central sensitization were investigated. Results: Only the latency of the P3 component after left wrist stimulation (t = -2.283; P = 0.023) differed between both groups. In CWAD patients, the ankle EPT correlated with the amplitude of the corresponding P1 (rho s = 0.293; P = 0.044) and P3 (rho s = 0.306; P = 0.033), as well as with the amplitude of the P3 to left wrist stimulation (rho s = 0.343; P = 0.017). Self-reported symptoms of CS correlated with right wrist P3 amplitude (rho s = 0.308; P = 0.030) and latency (rho s = -0.341; P = 0.015), and the worst pain reported during the past week was correlated with left wrist P1 latency (rho s = 0.319; P = 0.029). Limitations: Although the inclusion criteria stated that CWAD patients had to report a moderate-to-severe pain-related disability, 8 of the included CWAD patients (that scored above this threshold in the inclusion questionnaire), scored below the required cutoff at baseline. Conclusions: The CWAD patients did not show signs of hypersensitivity, but their ERP characteristics were related to the intensity of the applied stimulus, self-reported symptoms of CS, and the worst pain reported during the past week.

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Chronic pain is a leading cause of disability globally and associated with enormous health-care costs. The discrepancy between the extent of tissue damage and the magnitude of pain, disability, and associated symptoms represents a diagnostic challenge for rheumatology specialists. Central sensitisation, defined as an amplification of neural signalling within the CNS that elicits pain hypersensitivity, has been investigated as a reason for this discrepancy. Features of central sensitisation have been documented in various pain conditions common in rheumatology practice, including fibromyalgia, osteoarthritis, rheumatoid arthritis, Ehlers-Danlos syndrome, upper extremity tendinopathies, headache, and spinal pain. Within individual pain conditions, there is substantial variation among patients in terms of presence and magnitude of central sensitisation, stressing the importance of individual assessment. Central sensitisation predicts poor treatment outcomes in multiple patient populations. The available evidencesupports various pharmacological and non-pharmacological strategies to reduce central sensitisation and to improve patient outcomes in several conditions commonly seen in rheumatology practice. These data open up new treatment perspectives, with the possibility for precision pain medicine treatment according to pain phenotyping as a logical next step. With this view, studies suggest the possibility of matching non-pharmacological approaches, or medications, or both to the central sensitisation pain phenotypes.

Objectives: Literature has demonstrated inconsistent findings regarding the impact of parental responses on child pain-related outcomes. Yet, research into factors that may underlie inconsistent findings regarding the variable impact of parental responses is lacking. The current study investigated the moderating role of parental distress in understanding the impact of parental pain-attending (eg, reassuring the child) and non–pain-attending (eg, distracting the child with humor) responses on child pain behavior (eg, crying). Methods: Children (18 y and younger) with leukemia, undergoing a lumbar puncture (LP) and/or bone marrow aspiration procedure, and one of their parents, were recruited from the Pediatric Ghent University Hospital. Parent–child interactions were videotaped after the procedure allowing coding of parental responses and child pain behavior. Parents self-reported on experienced personal distress. Results: Participants consisted of 42 children (24 boys, 18 girls) with leukemia and one of their parents. Children were 0.6 to 15 (7.08±4.39) years old. Findings indicated a positive association between parental pain-attending and child pain behavior, but only when parents reported high levels of distress (β=0.56, P=0.001). No association was observed for parents reporting low levels of distress (β= −0.09, ns). Parental non–pain-attending responses contributed to lower child pain behavior (β=−0.24, P=0.045), independently of parental distress (β=−0.07, ns). Discussion: The current findings point to the moderating role of parental distress in understanding the impact of parental responses on child pain behavior and highlight the importance of interventions targeting parental emotion regulation to promote optimal child pain outcomes.

Objective: The objective of this cross-sectional study was to analyze the relationship between symptoms of central sensitization (CS) and important cognitive behavioral and psychosocial factors in a sample of patients with chronic nonspecific low back pain. Methods: Participants with chronic nonspecific low back pain for at least 3 months were included in the study. They completed several questionnaires and a functional test. Pearson's correlation was used to analyze associations between symptoms of CS and pain behavior, functioning, pain, pain catastrophizing, kinesiophobia, and illness perceptions. Additionally, a between-group analysis was performed to compare patients with and without clinically relevant symptoms of CS. Results: Data from 38 participants were analyzed. Significant associations were found between symptoms of CS and all other outcomes, especially current pain (r = 0.510, P=.001), mean pain during the past 7 days (r = 0.505, P=.001), and pain catastrophizing (r = 0.518, P=.001). Patients with clinically relevant symptoms of CS scored significantly worse on all outcomes compared with persons without relevant symptoms of CS, except on functioning (P=.128). Conclusions: Symptoms of CS were significantly associated with psychosocial and cognitive behavioral factors. Patients exhibiting a clinically relevant degree of symptoms of CS scored significantly worse on most outcomes, compared with the subgroup of the sample with fewer symptoms of CS.

Background: Scientific research has demonstrated impaired central pain modulation, cognitive and psychosocial deficits in patients with chronic whiplash associated disorders (CWAD). However, the underlying mechanisms remain unclear. To date, research regarding central pain modulation, cognitive performance and psychosocial characteristics in patients with chronic non-traumatic neck pain is lacking. Purpose: To examine central pain modulation (i.e. central sensitization), cognitive and psychosocial functioning in patients with CWAD and chronic idiopathic neck pain (CINP) compared to healthy individuals. Methods: Ninety-five women, 28 healthy pain-free controls, 35 CINP and 32 CWAD patients were enrolled. First, all participants filled out psychosocial questionnaires, namely the Short Form Health Survey (SF-36), the Neck Disability Index (NDI) and the Central Sensitization Inventory (CSI). Next, they were subjected to cognitive performance assessments and experimental pain measurements. Participants completedthe modified Perceived Deficits Questionnaire (mPDQ) in order to evaluate self-perceived cognitive deficits. Subsequently, they performed the Trail Making Test (TMT), an objective cognitive test. Afterwards, pressure pain thresholds (PPTs), and conditioned pain modulation (CPM) were examined. The Kruskal-Wallis test was applied to explore differences between all study groups. Post-hoc comparisons with a significance threshold of p

A growing body of research has demonstrated that impaired central pain modulation or central sensitization (CS) is a crucial mechanism for the development of persistent pain in chronic whiplash-associated disorders (WAD) and fibromyalgia (FM) patients. Furthermore, there is increasing evidence for cognitive dysfunctions among these patients. In addition, chronic WAD and FM patients often report problems with health-related quality of life (QoL). Yet, there is limited research concerning the interrelations between cognitive performance, indices of CS, and health-related QoL in these patients.(1) Examining the presence of cognitive impairment, CS, and limitations on health-related QoL in patients with chronic WAD and FM compared to healthy controls. (2) Examining interrelations between performance-based cognitive functioning, CS, and self-reported health-related QoL in these 3 study groups.A case-control study was conducted.The present study took place at the University Hospital Brussels, the University of Brussels, and the University of Antwerp.Fifty-nine patients (16 chronic WAD patients, 21 FM patients, and 22 pain-free volunteers) filled out the Short Form 36 item Health Survey (SF-36), a self-reported psychosocial questionnaire, to assess health-related QoL. Next, they were subjected to various pain measurements (pressure hyperalgesia, deep-tissue hyperalgesia, temporal summation [TS], and conditioned pain modulation [CPM]). Finally, participants completed a battery of performance-based cognitive tests (Stroop task, psychomotor vigilance task [PVT], and operation span task [OSPAN]).Significant cognitive impairment, bottom-up sensitization, and decreased health-related QoL were demonstrated in patients with chronic WAD and FM compared to healthy controls (P0.017). CPM was comparable between the 3 groups. Cognitive performance was significantly related to central pain modulation (deep-tissue hyperalgesia, TS, CPM) as well as to self-reported health-related QoL (P0.05). Decreased cognitive performance was related to deficient central pain modulation in healthy controls. Further, significant correlations between decreased cognitive performance and reduced health-related QoL were revealed among all study groups. Additionally, FM patients showed correlations between cognitive impairment and increased health-related QoL. Remarkably, impaired selective attention and working memory were related to less TS, whereas impaired sustained attention was correlated with dysfunctional CPM in FM patients.Based on the current cross-sectional study no firm conclusions can be drawn on the causality of the relations.In conclusion, this paper has demonstrated significant cognitive deficits, signs of CS, and reduced health-related QoL in chronic WAD and FM patients compared to healthy individuals. Significant relations between cognitive performance and CS as well as health-related QoL were demonstrated. These results provide preliminary evidence for the clinical importance of objectively measured cognitive deficits in patients with chronic WAD and FM.Chronic pain, fibromyalgia, whiplash, central sensitization, conditioned pain modulation, temporal summation, cognition, quality of life.

BACKGROUND: A growing body of research has demonstrated that impaired central pain modulation or central sensitization (CS) is a crucial mechanism for the development of persistent pain in chronic whiplash-associated disorders (WAD) and fibromyalgia (FM) patients. Furthermore, there is increasing evidence for cognitive dysfunctions among these patients. In addition, chronic WAD and FM patients often report problems with health-related quality of life (QoL). Yet, there is limited research concerning the interrelations between cognitive performance, indices of CS, and health-related QoL in these patients. OBJECTIVES: (1) Examining the presence of cognitive impairment, CS, and limitations on health-related QoL in patients with chronic WAD and FM compared to healthy controls. (2) Examining interrelations between performance-based cognitive functioning, CS, and self-reported health-related QoL in these 3 study groups. STUDY DESIGN: A case-control study was conducted. SETTING: The present study took place at the University Hospital Brussels, the University of Brussels, and the University of Antwerp. METHODS: Fifty-nine patients (16 chronic WAD patients, 21 FM patients, and 22 pain-free volunteers) filled out the Short Form 36 item Health Survey (SF-36), a self-reported psychosocial questionnaire, to assess health-related QoL. Next, they were subjected to various pain measurements (pressure hyperalgesia, deep-tissue hyperalgesia, temporal summation [TS], and conditioned pain modulation [CPM]). Finally, participants completed a battery of performance-based cognitive tests (Stroop task, psychomotor vigilance task [PVT], and operation span task [OSPAN]). RESULTS: Significant cognitive impairment, bottom-up sensitization, and decreased health-related QoL were demonstrated in patients with chronic WAD and FM compared to healthy controls (P < 0.017). CPM was comparable between the 3 groups. Cognitive performance was significantly related to central pain modulation (deep-tissue hyperalgesia, TS, CPM) as well as to self-reported health-related QoL (P < 0.05). Decreased cognitive performance was related to deficient central pain modulation in healthy controls. Further, significant correlations between decreased cognitive performance and reduced health-related QoL were revealed among all study groups. Additionally, FM patients showed correlations between cognitive impairment and increased health-related QoL. Remarkably, impaired selective attention and working memory were related to less TS, whereas impaired sustained attention was correlated with dysfunctional CPM in FM patients. LIMITATIONS: Based on the current cross-sectional study no firm conclusions can be drawn on the causality of the relations. CONCLUSION: In conclusion, this paper has demonstrated significant cognitive deficits, signs of CS, and reduced health-related QoL in chronic WAD and FM patients compared to healthy individuals. Significant relations between cognitive performance and CS as well as health-related QoL were demonstrated. These results provide preliminary evidence for the clinical importance of objectively measured cognitive deficits in patients with chronic WAD and FM. KEY WORDS: Chronic pain, fibromyalgia, whiplash, central sensitization, conditioned pain modulation, temporal summation, cognition, quality of life.

Objectives Delayed recovery of muscle function following exercise has been demonstrated in the lower limbs of patients with multiple sclerosis (MS). However, studies examining this in the upper limbs are currently lacking. This study compared physical activity level (PAL) and recovery of upper limb muscle function following exercise between MS patients and healthy inactive controls. Furthermore, the relationship between PAL and muscle recovery was examined. Methods PAL of 19 MS patients and 32 controls was measured using an accelerometer for 7 consecutive days. Afterwards, recovery of muscle function was assessed by performing a fatiguing upper limb exercise test with subsequent recovery measures. Results Muscle recovery of the upper limb muscles was similar in both groups. Average activity counts were significantly lower in MS patients than in the control group. MS patients spent significantly more time being sedentary and less time on activities of moderate intensity compared with the control group. Nosignificant correlation between PAL and recovery of muscle function was found in MS patients. Conclusions Recovery of upper limb muscle function following exercise is normal in MS patients. MS patients are less physically active than healthy inactive controls. PAL and recovery of upper limb muscle function appear unrelated in MS patients.

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Background. Besides self-reported cognitive complaints, sufficient evidence exists to support the presence of performance-based cognitive impairments in individuals with chronic whiplash-associated disorders (WAD). While it is well known that exercise can have positive effects on cognitive performance in healthy persons, these effects are still unclear in chronic WAD patients. Aims. This study aimed at examining the effect of an acute exercise bout on chronic WAD patients' cognitive performance. Methods. Twenty-seven patients with chronic WAD and 27 healthy controls completed two performance-based cognitive tests assessing selective and sustained attention, cognitive inhibition, and simple and choice reaction time (RT). Tests were performed immediately before and after an acute submaximal exercise on a cycle ergometer. All participants signed written informed consent. Results. There was no significant difference among chronic WAD patients and healthy controls for selective attention, cognitive inhibition, and choice RT (P>0.05). However, chronic WAD patients displayed significant deficits in sustained attention and simple RT compared with healthy controls (P Conclusions. This is the first study examining the effect of exercise on cognitive performance in chronic WAD. The results indicate subtle cognitive deficits in terms of impaired vigilance in chronic WAD patients compared with healthy controls. However, our data suggest a similar response to acute submaximal exercise in terms of cognitive performance in chronic WAD patients and healthy controls.

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Objectives. If the somatosensory input and the predicted motor output are in conflict, it causes a sensorimotor incongruence and this may serve as an ongoing source of nociception inside the central nervous system. Sensorimotor incongruence exacerbates symptoms in patients with chronic whiplash associated disorders (WAD). This study aimed to evaluate whether visually feedback and visual mediated incongruence between motor output and sensory input of the neck region influences the pain thresholds in chronic WAD. Methods. Thirty patients with chronic WAD and 30 healthy controls were subjected to an experiment with four phases of a visual feedback test in random order. They watched a monitor with real-time visual feedback of the neck-shoulder region without movement or with simultaneous lateroflexion of the neck. Modified visual feedback was used to create sensorimotor incongruence. Pain pressure thresholds (PPT) at the neck/shoulder and thigh were measured during each of the phases. Results. Real-timevisual feedback triggered a significant increase in PPT in healthy controls. In contrast, feedback of the neck and shoulder region did not alter PPT's in chronic WAD. The sensory and sensorimotor conflict did not result in a different PPT response as compared to the correct visual feedback. Conclusion. Contrary to healthy controls, visual feedback was not able to influence the pain thresholds in the neck/shoulder region or the thigh in chronic WAD. These findings indicate an abnormal pain response to visual feedback at rest and during neck movement in chronic WAD. Experimentally-induced sensorimotor incongruence did not alter pain thresholds in chronic WAD.

Patients with acute whiplash associated disorders (WAD) demonstrate an inefficient endogenous pain inhibition and possibly a dysfunction in autonomic nervous system. The goal of this study was to compare the autonomic response to painful stimuli between patients with acute WAD to chronic WAD and healthy controls. And to explore the role of the autonomic parameters in the inefficient endogenous pain inhibition in acute WAD together with the possible role of post-traumatic stress response. Seventeen patients with acute WAD, thirty patients with chronic WAD and thirty-one healthy controls were subjected to an experiment evaluating the autonomic nervous system at rest and during experimental painful stimuli. Skin conductance, heart rate and heart rate variability (HRV) parameters were monitored continuously during the evaluation of conditioned pain modulation. The paradigm of heterotopic noxious conditioning stimulation was used to assess this conditioned pain modulation effect. A significant autonomic response to pain was present for skin conductance and two heart rate variability parameters in all experimental groups. There was an interaction effect of the skin conductance response to pain, but no difference in HRV responses to pain in any of the groups. In patients with acute WAD, no significant correlations were present between pain, pressure pain thresholds, pain inhibition and any of the autonomic parameters. Results of this study refutes autonomic dysfunction in response to pain in both acute and chronic WAD. The dysfunctional conditioned pain modulation as typically seen in patients with acute and chronic WAD, appears unrelated to autonomic responses to pain.

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Kelly Ickmans: Cognitive Impairment in Adults with Chronic Pain and/or Fatigue. Kelly holds a master of science degree and is physiotherapist and PhD researcher in the Pain in Motion research group (www.paininmotion.be), Vrije Universiteit Brussel, Belgium. Her research is focused on exercise and cognitive (dys) functioning in chronic pain patients. She has published 10 papers in peer reviewed international journals, the majority of which address chronic fatigue syndrome. The role that exercise and indices of physical status play with regard to cognitive (dys) function in this patient population will be discussed.

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BACKGROUND: Although enhanced temporal summation (TS) and conditioned pain modulation (CPM), as characteristic for central sensitization, has been proved to be impaired in different chronic pain populations, the exact nature is still unknown. OBJECTIVES: We examined differences in TS and CPM in 2 chronic pain populations, patients with both chronic fatigue syndrome (CFS) and comorbid fibromyalgia (FM) and patients with rheumatoid arthritis (RA), and in sedentary, healthy controls, and evaluated whether activation of serotonergic descending pathways by acetaminophen improves central pain processing. STUDY DESIGN: Double-blind randomized controlled trial with cross-over design. METHODS: Fifty-three women (19 CFS/FM patients, 16 RA patients, and 18 healthy women) were randomly allocated to the experimental group (1 g acetaminophen) or the placebo group (1 g dextrose). Participants underwent an assessment of endogenous pain inhibition, consisting of an evaluation of temporal summation with and without conditioned pain modulation (CPM). Seven days later groups were crossed-over. Patients and assessors were blinded for the allocation. RESULTS: After intake of acetaminophen, pain thresholds increased slightly in CFS/FM patients, and decreased in the RA and the control group. Temporal summation was reduced in the 3 groups and CPM at the shoulder was better overall, however only statistically significant for the RA group. Healthy controls showed improved CPM for both finger and shoulder after acetaminophen, although not significant. LIMITATIONS: The influence of acetaminophen on pain processing is inconsistent, especially in the patient groups examined. CONCLUSION: This is the first study comparing the influence of acetaminophen on central pain processing in healthy controls and patients with CFS/FM and RA. It seems that CFS/FM patients present more central pain processing abnormalities than RA patients, and that acetaminophen may have a limited positive effect on central pain inhibition, but other contributors have to be identified and evaluated.

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Association between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome. [J Rehabil Res Dev. 2013] Rebuttal to Ickmans et al. association between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome. J Rehabil Res Dev. 2013;50(6):795-810. www.rehab.research.va.gov/jour/ 2013/506/pdf/ickmans506.pdf.

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