Measuring sensory and pain thresholds by Semmes-Weinstein monofilaments in patients with leg ulcers: a pilot study.

OBJECTIVE: Pain is a common and disabling symptom in patients with leg ulcers. Clinical quantification of pain mostly depends on subjective pain reports, which do not reveal underlying mechanisms. The aim of this pilot study is to identify mechanisms underlying the pain in patients with leg ulcers by documenting alterations in pain processing using quantitative sensory testing. METHODS: In nine ulcer patients the mechanical sensory thresholds and the mechanical pain thresholds were determined by Semmes-Weinstein monofilaments (SWM) at three different sites: on the contralateral (unaffected) leg, on the skin of the affected leg 10cm from the ulcer margin, and on the affected leg, close (1-2cm) to the ulcer margin. Besides the mechanical sensory thresholds and mechanical pain thresholds, pain at the site of the ulcer, using an 11-point numeric rating scale (NRS), was documented. RESULTS: Mechanical sensory thresholds were increased in all subjects. Almost half (44%) of patients consistently showed allodynia at the unaffected site. The lowering of mechanical pain thresholds correlated with higher scores on the NRS. CONCLUSION: All patients showed diminished touch and/or protective sensation, which might have contributed to ulcer development via (partial) loss of protective function. The allodynia at the unaffected site suggests the presence of central sensitisation of pain processing.

The added value of bedside examination and screening QST to improve neuropathic pain identification in patients with chronic pain.

BACKGROUND: The assessment of a neuropathic pain component (NePC) to establish the neurological criteria required to comply with the clinical description is based on history taking, clinical examination, and quantitative sensory testing (QST) and includes bedside examination (BSE). The objective of this study was to assess the potential association between the clinically diagnosed presence or absence of an NePC, BSE, and the Nijmegen-Aalborg screening QST (NASQ) paradigm in patients with chronic (≥3 months) low back and leg pain or with neck shoulder arm pain or in patients with chronic pain due to suspected peripheral nerve damage. METHODS: A total of 291 patients participated in the study. Pain (absence or presence of neuro-pathic pain) was assessed independently by two physicians and compared with BSE (measurements of touch [finger, brush], heat, cold, pricking [safety pin, von Frey hair], and vibration). The NASQ paradigm (pressure algometry, electrical pain thresholds, and conditioned pain modulation) was assessed in 58 patients to generate new insights. RESULTS: BSE revealed a low association of differences between patients with either absent or present NePC: heat, cold, and pricking sensations with a von Frey hair were statistically significantly less common in patients with present NePC. NASQ did not reveal any differences between patients with and without an NePC. CONCLUSION: Currently, a standardized BSE appears to be more useful than the NASQ paradigm when distinguishing between patients with and without an NePC.

Influence of exercise on visceral pain: an explorative study in healthy volunteers.

BACKGROUND AND OBJECTIVES: Contradictory results have been found about the effect of different exercise modalities on pain. The aim of this study was to investigate the early effects of aerobic and isometric exercise on different types of experimental pain, including visceral pain, compared to an active control condition. METHODS: Fifteen healthy subjects (6 women, mean [standard deviation] age 25 [6.5] years) completed 3 interventions consisting of 20 minutes of aerobic cycling, 12 minutes of isometric knee extension and a deep breathing procedure as active control. At baseline and after each intervention, psychophysical tests were performed, including electrical stimulation of the esophagus, pressure pain thresholds and the cold pressor test as a measure for conditioned pain modulation. Participants completed the Medical Outcome Study Short-Form 36 and State-Trait Anxiety Inventory prior to the experiments. Data were analyzed using two-way repeated measures analysis of variance. RESULTS: No significant differences were found for the psychophysical tests after the interventions, compared to baseline pain tests and the control condition. CONCLUSION: No hypoalgesic effect of aerobic and isometric exercise was found. The evidence for exercise-induced hypoalgesia appears to be not as consistent as initially thought, and caution is recommended when interpreting the effects of exercise on pain.

Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients.

BACKGROUND: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders) to placebo or pregabalin treatment. METHODS: This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients were assigned to one of four groups, ie, responders and nonresponders to pregabalin (n=16; n=15) or placebo (n=12; n=17) treatment. Responders were defined as patients with >30% pain reduction after 3 weeks of treatment. We measured change in pain sensitivity before and after the treatment using electric pain detection thresholds (ePDT) in dermatomes C5 (generalized effects) and Ventral T10 (segmental effects). Descending endogenous pain modulation was quantified via conditioned pain modulation (CPM) paradigm. RESULTS: Sixty patients were analyzed in a per-protocol analysis. ePDT change in C5 was significant vs baseline and greater in pregabalin (1.3 mA) vs placebo responders (-0.1 mA; P=0.015). This was not so for ePDT in Ventral T10. CPM increased more in pregabalin (9%) vs placebo responders (-17%; P<0.001). CPM changed significantly vs baseline only for pregabalin responders (P=0.006). CONCLUSION: This hypothesis-generating study provides the first evidence that pain relief with pregabalin is associated with anti-hyperalgesic effects and increased endogenous inhibitory modulation. No such effects were observed in patients experiencing pain relief with the placebo treatment. The mechanisms underlying analgesic response to placebo vs drug treatments are different and, together with their interactions, deserve further study.

Altered resting state EEG in chronic pancreatitis patients: toward a marker for chronic pain.

OBJECTIVES: Electroencephalography (EEG) may be a promising source of physiological biomarkers accompanying chronic pain. Several studies in patients with chronic neuropathic pain have reported alterations in central pain processing, manifested as slowed EEG rhythmicity and increased EEG power in the brain's resting state. We aimed to investigate novel potential markers of chronic pain in the resting state EEG of patients with chronic pancreatitis. PARTICIPANTS: Resting state EEG data from 16 patients with persistent abdominal pain due to chronic pancreatitis (CP) were compared to data from healthy controls matched for age, sex and education. METHODS: The peak alpha frequency (PAF) and power amplitude in the alpha band (7.5-13 Hz) were compared between groups in four regions of interest (frontal, central, parietal, and occipital) and were correlated with pain duration. RESULTS: The average PAF was lowered in CP patients compared with that in healthy controls, observed as a statistically significant between-group effect (mean 9.9 versus 9.5 Hz; P=0.049). Exploratory post hoc analysis of average PAF per region of interest revealed a significant difference, particularly in the parietal and occipital regions. In addition, we observed a significant correlation between pain duration and PAF and showed increased shifts in PAF with longer pain durations. No significant group differences were found in peak power amplitudes. CONCLUSION: CP pain is associated with alterations in spontaneous brain activity, observed as a shift toward lower PAF. This shift correlates with the duration of pain, which demonstrates that PAF has the potential to be a clinically feasible biomarker for chronic pain. These findings could be helpful for assisting diagnosis, establishing optimal treatment, and studying efficacy of new therapeutic agents in chronic pain patients.

Patients with persistent pain after breast cancer surgery show both delayed and enhanced cortical stimulus processing.

BACKGROUND: Women who undergo breast cancer surgery have a high risk of developing persistent pain. We investigated brain processing of painful stimuli using electroencephalograms (EEG) to identify event-related potentials (ERPs) in patients with persistent pain after breast cancer treatment. METHODS: Nineteen patients (eight women with persistent pain, eleven without persistent pain), who were surgically treated more than 1 year previously for breast cancer (mastectomy, lumpectomy, and axillary lymph node dissection) and/or had chemoradiotherapy, were recruited and compared with eleven healthy female volunteers. A block of 20 painful electrical stimuli was applied to the calf, somatopically remote from the initially injured or painful area. Simultaneously an EEG was recorded, and a visual analog scale (VAS) pain rating obtained. RESULTS: In comparison with healthy volunteers, breast cancer treatment without persistent pain is associated with accelerated stimulus processing (reduced P260 latency) and shows a tendency to be less intense (lower P260 amplitude). In comparison to patients without persistent pain, persistent pain after breast cancer treatment is associated with stimulus processing that is both delayed (ie, increased latency of the ERP positivity between 250-310 ms [P260]), and enhanced (ie, enhanced P260 amplitude). CONCLUSION: These results show that treatment and persistent pain have opposite effects on cortical responsiveness.

Neural correlates of heterotopic facilitation induced after high frequency electrical stimulation of nociceptive pathways.

BACKGROUND: High frequency electrical stimulation (HFS) of primary nociceptive afferents in humans induce a heightened sensitivity in the surrounding non-stimulated skin area. Several studies suggest that this heterotopic effect is the result of central (spinal) plasticity. The aim of this study is to investigate HFS-induced central plasticity of sensory processing at the level of the brain using the electroencephalogram (EEG). To this end we measured evoked potentials in response to noxious electrical pinprick-like stimuli applied in the heterotopic skin area before, directly after and 30 minutes after HFS. RESULTS: We observed potential cortical electrophysiological correlates of heterotopic facilitation. Two different cortical correlates were found; the first one was a lateralized effect, i.e. a larger N100 amplitude on the conditioned arm than the control arm 30 minutes after end of HFS. This was comparable with the observed lateralized effect of visual analogue scale (VAS) scores as response to the mechanical punctate stimuli. The second correlate seems to be a more general (non-lateralized) effect, because the result affects both arms. On average for both arms the P200 amplitude increased significantly 30 minutes after end of HFS with respect to baseline. CONCLUSIONS: We suggest that for studying heterotopic nociceptive facilitation the evoked brain response is suitable and relevant for investigating plasticity at the level of the brain and is perhaps a more sensitive and reliable marker than the perceived pain intensity (e.g. VAS).