Kristian Bernhard Nilsen

Recommendations on practice of conditioned pain modulation (CPM) testing

Protocols for testing conditioned pain modulation (CPM) vary between different labs/clinics. In order to promote research and clinical application of this tool, we summarize the recommendations of interested researchers consensus meeting regarding the practice of CPM and report of its results.

Two novel SCN9A mutations causing insensitivity to pain.

The sensation of pain is important and there may be serious consequences if it is missing. Recently, the genetic basis for a channelopathy characterised by a congenital inability to experience pain has been described and channelopathy-associated insensitivity to pain has been proposed as a suitable name for this condition. Different mutations in the SCN9A gene causing loss of function of the voltage-gated sodium channel Nav1.7 have been reported in patients with this rare disease. Here we describe a woman with insensitivity to pain with two novel mutations in the SCN9A gene, coding for the Nav1.7 channel. We also discuss the finding of anosmia which apparently is a common feature in these patients.

Autonomic activation and pain in response to low‐grade mental stress in fibromyalgia and shoulder/neck pain patients

Objective: Psychosocial stress is a risk factor for musculoskeletal pain, but how stress affects musculoskeletal pain is poorly understood. We wanted to examine the relationship between low‐grade autonomic activation and stress‐related pain in patients with fibromyalgia and localised chronic shoulder/neck pain.

Pain induced by low-grade stress in patients with fibromyalgia and chronic shoulder/neck pain, relation to surface electromyography

The mechanisms of pain causation in fibromyalgia (FMS) and chronic shoulder/neck pain (SNP) are still debated. We wanted to compare muscle activity and pain development during and after low‐grade mental stress in FMS and SNP patients. Twenty‐three women with FMS, 29 women with chronic SNP and 35 healthy women performed a stressful task lasting 60 min followed by a 30 min recovery period. We recorded surface electromyography over the trapezius, neck, temporalis and frontalis muscles. Subjects reported their pain at the corresponding locations together with the development of fatigue and perceived tension. Significant differences between FMS and SNP groups were not observed either for muscular or subjective responses. SNP patients and controls responded with more pain in the trapezius and neck regions than in the forehead, in contrast to FMS patients who had a more generalized pain response. Development of pain, tension and fatigue was not related to muscle activity for any group. We conclude that FMS and SNP patients have similar pain and electromyographic responses. The results suggest that similar pathophysiological mechanisms are involved although the responses are more generalised in FMS than in SNP patients. Muscular activity did not explain the pain which developed during the stressful task for either group. Pain lasted longer during recovery in both FMS and SNP patients compared to healthy controls, possibly a result of disease‐related sensitisation in pain pathways.

Thermal pain thresholds are decreased in the migraine preattack phase

Background and purpose:  Migraine patients may have cutaneous allodynia during attacks. In order to investigate if pain physiology changes in the preattack phase we estimated heat pain and cold pain detection threshold (HPT and CPT) on three different days in 41 migraine patients and 28 controls.

Visual Evoked Potentials in Interictal Migraine: No Confirmation of Abnormal Habituation

We intended to study the effect of check size on visual evoked potential habituation in interictal migraine, using the faster 3 per second reversal rate and an improved analytic procedure with block‐number blinding.

The Effects of Long-Term Oral Benfotiamine Supplementation on Peripheral Nerve Function and Inflammatory Markers in Patients With Type 1 Diabetes A 24-month, double-blind, randomized, placebo-controlled trial

OBJECTIVE To study the effects of long-term oral benfotiamine supplementation on peripheral nerve function and soluble inflammatory markers in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS The study randomly assigned 67 patients with type 1 diabetes to receive 24-month benfotiamine (300 mg/day) or placebo supplementation. Peripheral nerve function and levels of soluble inflammatory variables were assessed at baseline and at 24 months. RESULTS Fifty-nine patients completed the study. Marked increases in whole-blood concentrations of thiamine and thiamine diphosphate were found in the benfotiamine group (both P < 0.001 vs. placebo). However, no significant differences in changes in peripheral nerve function or soluble inflammatory biomarkers were observed between the groups. CONCLUSIONS Our findings suggest that high-dose benfotiamine (300 mg/day) supplementation over 24 months has no significant effects upon peripheral nerve function or soluble markers of inflammation in patients with type 1 diabetes.

Autonomic and muscular responses and recovery to one-hour laboratory mental stress in healthy subjects

BackgroundStress is a risk factor for musculoskeletal pain. We wanted to explore stress related physiology in healthy subjects in order to gain insight into mechanisms of pain development which may relate to the pathophysiology of musculoskeletal pain disorders.MethodsContinuous blood pressure, heart rate, finger skin blood flow, respiration, surface electromyography together with perception of pain, fatigue and tension were recorded on 35 healthy women and 9 healthy men before, during a 60 minute period with task-related low-grade mental stress, and in the following 30 minute rest period.ResultsSubjects responded physiologically to the stressful task with an increase in trapezius and frontalis muscle activity, increased blood pressure, respiration frequency and heart rate together with reduced finger skin blood flow. The blood pressure response and the finger skin blood flow response did not recover to baseline values during the 30-minute rest period, whereas respiration frequency, heart rate, and surface electromyography of the trapezius and frontalis muscles recovered to baseline within 10 minutes after the stressful task. Sixty-eight percent responded subjectively with pain development and 64% reported at least 30% increase in pain. Reduced recovery of the blood pressure was weakly correlated to fatigue development during stress, but was not correlated to pain or tension.ConclusionBased on a lack of recovery of the blood pressure and the acral finger skin blood flow response to mental stress we conclude that these responses are more protracted than other physiological stress responses.

Noradrenaline and cortisol changes in response to low-grade cognitive stress differ in migraine and tension-type headache

The goal of this study was to explore the relationship between indicators of sympathoneural, sympathomedullar and hypothalamic-pituitary-adrenocortical (HPA) activity and stress-induced head and shoulder-neck pain in patients with migraine or tension-type headache (TTH). We measured noradrenaline, adrenaline and cortisol levels before and after low-grade cognitive stress in 21 migraineurs, 16 TTH patients and 34 controls. The stressor lasted for 60 min and was followed by 30 min of relaxation. Migraine patients had lower noradrenaline levels in blood platelets compared to controls. Pain responses correlated negatively with noradrenaline levels, and pain recovery correlated negatively with the cortisol change in migraineurs. TTH patients maintained cortisol secretion during the cognitive stress as opposed to the normal circadian decrease seen in controls and migraineurs. There may therefore be abnormal activation of the HPA axis in patients with TTH when coping with mental stress, but no association was found between pain and cortisol. A relationship between HPA activity and stress in TTH patients has to our knowledge not been reported before. In migraine, on the other hand, both sympathoneural activation and HPA activation seem to be linked to stress-induced muscle pain and recovery from pain respectively. The present study suggests that migraineurs and TTH patients cope differently with low-grade cognitive stress.

The effect of sleep restriction on laser evoked potentials, thermal sensory and pain thresholds and suprathreshold pain in healthy subjects

OBJECTIVE Sleep restriction seems to change our experience of pain and reduce laser evoked potential (LEP) amplitudes. However, although LEP-habituation abnormalities have been described in painful conditions with comorbid sleep impairment, no study has previously measured the effect of sleep restriction on LEP-habituation, pain thresholds, and suprathreshold pain. METHOD Sixteen males and seventeen females (aged 18-31years) were randomly assigned to either two nights of delayed bedtime and four hours sleep (partial sleep deprivation) or nine hours sleep. The study subjects slept at home, and the sleep was measured with actigraphy both nights and polysomnography the last night. LEP, thermal thresholds and suprathreshold pain ratings were obtained the day before and the day after intervention. The investigator was blinded. ANOVA was used to evaluate the interaction between sleep restriction and day for each pain-related variable. RESULTS LEP-amplitude decreased after sleep restriction (interaction p=0.02) compared to subjects randomized to nine hours sleep. LEP-habituation was similar in both groups. Thenar cold pain threshold decreased after sleep restriction (interaction p=0.009). Supra-threshold heat pain rating increased temporarily 10s after stimulus onset after sleep restriction (interaction p=0.01), while it did not change after nine hours sleep. CONCLUSION Sleep restriction reduced the CNS response to pain, while some of the subjective pain measures indicated hyperalgesia. SIGNIFICANCE Since LEP-amplitude is known to reflect both CNS-pain-specific processing and cognitive attentive processing, our results suggest that hyperalgesia after sleep restriction might partly be caused by a reduction in cortical cognitive or perceptual mechanisms, rather than sensory amplification.