Qualitative and Quantitative Aspects of Pain in Patients With Myotonic Dystrophy Type 2

Pain is a common but often ignored symptom in patients with myotonic dystrophy type 2 (DM2). In this explorative study, we assessed qualitative and quantitative aspects of pain in DM2 using 4 questionnaires and quantitative sensory testing. A disease control group (fibromyalgia [FMS]) as well as healthy controls were used to compare the results, because pain in DM2 shows many clinical similarities to pain in FMS. Thirty-four patients with genetically confirmed DM2 (71% female, mean age 54 years), 28 patients with FMS, and 33 healthy controls were included, age- as well as sex-matched. Pain prevalence was 65% in DM2, 100% in FMS (P?<?.001), and 15% in healthy controls (P?<?.001). The mean of the pressure pain thresholds was lower in DM2 than in healthy controls (P?=?.016), with the largest differences in the rectus femoris, trapezius, and thenar muscles. Mechanical and electric pain thresholds were significantly higher in DM2 than in FMS, and no differences were found in electric pain thresholds between DM2 and healthy controls. These results confirm that pain is a frequent and important symptom in patients with DM2, affecting quality of life. Peripheral mechanisms of pain seem to play a role in DM2. The widespreadness of the hyperalgesia suggests central sensitization, but this finding was not supported by the other results. This study opens new avenues for further research and eventually novel treatment strategies, in DM2 as well as in other muscular disorders.

Differential central pain processing following repetitive intramuscular proton/prostaglandin E2 injections in female fibromyalgia patients and healthy controls

Background: While the etiology of fibromyalgia syndrome (FMS) remains unclear, it is assumed that both peripheral and central components are involved. Aims/methods: To investigate central activation patterns following chemically‐induced muscle pain we repetitively injected protons (low pH) and prostaglandin E₂ (PGE₂) in isotonic solution into the left extensor carpi radialis brevis muscle of female FMS patients and female healthy control subjects (HC). The injection of protons/PGE₂ has the advantage that it is not prone to tachyphylaxis compared to capsaicin and hypotonic saline solution. During the repetitive injections continuous pain ratings were recorded and functional magnetic resonance imaging measurements were conducted. Results: Injection of protons/PGE₂ led to activation of the anterior and medial cingulate cortices, contralateral primary sensory cortex, bilateral insula and thalamus, left basal ganglia, left orbitofrontal cortex and the cerebellum in FMS patients. In HC, activations were found only in the anterior, medial, and posterior cingulate cortices, and the primary somatosensory cortex. The contrast between the groups revealed significantly stronger activation for FMS patients in the left anterior insula. Peak pain ratings were comparable between HC and FMS patients, but pain duration (sustained pain) was prolonged in FM. Conclusion: Repetitive proton/PGE₂‐induced excitation of muscle tissue led to a more prolonged perception of pain and more wide‐spread activation in pain‐related brain areas in FMS, especially in the left (ipsilateral) insula, whereas acute protons/PGE₂‐induced pain processing was similar in the two groups. These data provide further evidence for enhanced central pain processing in FMS patients.     

Depression and changed pain perception: hints for a central disinhibition mechanism

Although patients with a depressive disorder report often of pain, their sensitivity to experimental pain is controversial, probably due to differences in sensory testing methods and to the lack of normal values. Therefore, we used a standardized and validated comprehensive sensory testing paradigm to assess the peripheral and central nervous system performance in depressive patients compared to healthy controls and chronic pain patients with fibromyalgia syndrome (FMS), in which depression is a common comorbidity. Twenty-five depressive psychiatric inpatients (pain-free: n=20), 35 FMS outpatients and 25 healthy controls underwent quantitative sensory testing (QST), including thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimuli (wind-up). In depressive disorder (to a lesser extent also in FMS), significantly decreased cold pain thresholds and an increased wind-up were found, although the mechanical pain thresholds and pain sensitivity were comparable to those of the healthy controls. All the detection thresholds were within the normal range in all the groups. In depressive disorder, there were no significant side differences in the detection and pain thresholds. The results contradict the former assumption of a general insensitivity to experimental pain in depressive disorder. In the mostly pain-free patients signs of an enhanced central hyperexcitability are even more pronounced than usually found in chronic pain patients (e.g. FMS), indicating common mechanisms in depressive disorder and chronic pain in accordance with the assumption of non-pain associated mechanisms in depressive disorder for central hyperexcitability, e.g. by inhibited serotonergic function. Furthermore, this trial demonstrates the feasibility of QST in depressive patients.     

Altered brain activity during pain processing in fibromyalgia

Fibromyalgia syndrome (FMS) is characterized by widespread pain. Studies with functional neuroimaging support the hypothesis of central pain augmentation in FMS. We tested this in our study with a novel paradigm of tonic pain induced by a single stimulus. Tonic pain, in contrast to phasic pain, seems to be a more appropriate experimental approach to study adaptive mechanisms of pain processing in FMS. We hypothesized that brain areas related to the "medial" pain system and the amygdalae will present different activation in patients compared to healthy subjects. An fMRI-block design before, during and after an incision was made in patients with FMS and in healthy controls. Acute pain caused by the incision was measured during the course of the experiment. A 2 factorial model of BOLD-signal changes was designed to explore significant differences of brain activation between both groups during the pain stimulus. Additionally the first Eigenvariates in those areas which show an interaction between both factors were determined over the time course of pain stimulation. Differences of activation in the fronto-cingulate cortex, the supplemental motor areas, and the thalamus were found between both groups with distinct differences in BOLD-signals changes over the time course of pain stimulation, even during anticipation of pain. Our results support the hypothesis that central mechanisms of pain processing in the medial pain system, favourable cognitive/affective factors even during the anticipation of pain, may play an important role for pain processing in patients with FMS.     

Enhanced central pain processing of fibromyalgia patients is maintained by muscle afferent input: A randomized, double-blind, placebo-controlled study

Fibromyalgia (FM) syndrome is characterized by pain and widespread hyperalgesia to mechanical, thermal, and electrical stimuli. Despite convincing evidence for central sensitization of nociceptive pain pathways, the role of peripheral tissue impulse input in the initiation and maintenance of FM is unclear. Therefore this randomized, double-blind, placebo-controlled trial of 22 female normal controls (NCs) and 28 female FM subjects tested the effects of trapezius muscle (TrapM) tender point injections with 1% lidocaine on local pain thresholds as well as on remote heat hyperalgesia at the forearm. Prior to muscle injections shoulder pain was standardized by tonic mechanical muscle stimulation, resulting in local pain ratings of 4.0 ± 0.5 VAS units. Tonic muscle stimulation was interrupted for the TrapM injections but was continued afterwards at the same level. NC as well as FM subjects experienced significant increases of TrapM pressure pain thresholds from lidocaine injections but not from placebo injections (p < 0.001). Additionally, heat hyperalgesia of FM participants was significantly reduced at areas remote from the injection site (forearm) by lidocaine but not by placebo (p = 0.02). Neither lidocaine nor saline injections significantly affected clinical FM pain ratings, a result most likely due to the very low dose of lidocaine (50 mg) used in this trial. Conclusion: Lidocaine injections increased local pain thresholds and decreased remote secondary heat hyperalgesia in FM patients, emphasizing the important role of peripheral impulse input in maintaining central sensitization in this chronic pain syndrome; similar to other persistent pain conditions such as irritable bowel syndrome and complex regional pain syndrome.     

Improvement in clinical outcomes after dry needling versus myofascial release on pain pressure thresholds,quality of life,fatigue, pain intensity,quality of sleep,anxiety, and depression in patients with fibromyalgia syndrome

Purpose: To compare the effectiveness of dry needling versus myofascial release on myofascial trigger points pain in cervical muscles, quality of life, impact of symptoms pain, quality of sleep, anxiety, depression, and fatigue in patients with fibromyalgia syndrome.

Method: A single-blind randomized controlled trial was conducted. Sixty-four subjects with fibromyalgia were randomly assigned to a dry needling group or a myofascial release group. Pain pressure thresholds of myofascial trigger points were evaluated in the cervical muscles. In addition, quality of life, impact of fibromyalgia symptoms, quality of sleep, intensity of pain, anxiety and depression symptoms, impact of fatigue at baseline and post treatment after four weeks of intervention were evaluated.

Results: Significant improvement was found in most pain pressure thresholds of the myofascial trigger points in cervical muscles in the dry needling group compared to myofascial release (p?<?0.05). Similarly, these differences between groups were found for the components of quality of life of physical function (F?=?12.74, p?=?0.001), physical role (F?=?11.24, p?=?0.001), body pain (F?=30.26, p?<?0.001), general health (F?=?15.83, p?<?0.001), vitality (F?=?13.51, p?=?0.001), social function (F?=?4.73, p?=?0.034), emotional role (F?=?8.01, p?=?0.006), and mental health (F?=?4.95, p?=?0.030). Similar results were achieved for total impact of FMS symptoms (F?=?42.91, p?<?0.001), quality of sleep (F?=?11.96, p?=?0.001), state anxiety (F?=?7.40, p?=?0.009), and trait anxiety (F?=??14.63, p?<?0.001), hospital anxiety and depression (F?=?20.60, p?<?0.001), general pain intensity (F?=?29.59, p?<?0.001), and fatigue (F?=??25.73, p?<?0.001).

Conclusion: The dry needling therapy showed higher improvements in comparison with myofascial release therapy for pain pressure thresholds, the components of quality of life of physical role, body pain, vitality and social function, as well as the total impact of FMS symptoms, quality of sleep, state and trait anxiety, hospital anxiety-depression, general pain intensity and fatigue.

• Implications for rehabilitation

• Dry needling therapy reduces myofascial trigger point pain in the short term in patients with fibromyalgia syndrome.

• This therapeutic approach improves anxiety, depression, fatigue symptoms, quality of life, and sleep after treatment.

• Dry needling and myofascial release therapies decrease intensity of pain, and the impact of fibromyalgia symptoms in this population.

• These intervention approaches should be considered in an independent manner as complementary therapies within a multidisciplinary setting.

     

Sleep continuity and architecture: Associations with pain‐inhibitory processes in patients with temporomandibular joint disorder

Recent research suggests bi‐directional interactions between the experience of pain and the process of sleep; pain interferes with the ability to obtain sleep, and disrupted sleep contributes to enhanced pain perception. Our group recently reported, in a controlled experimental study, that sleep fragmentation among healthy adults resulted in subsequent decrements in endogenous pain inhibition. The present report follows up that observation by extending this line of research to a sample of patients experiencing persistent pain. Patients with chronic temporomandibular joint disorder (TMD) pain were studied using polysomnography and psychophysical evaluation of pain responses. We assessed whether individual differences in sleep continuity and/or architecture were related to diffuse noxious inhibitory controls (DNIC), a measure of central nervous system pain inhibition. Among 53 TMD patients, higher sleep efficiency and longer total sleep time were positively associated with better functioning of DNIC (r = 0.42–0.44, p < 0.01; ps < 0.05 for the multivariate analyses). These results suggest the possibility that disrupted sleep may serve as a risk factor for inadequate pain‐inhibitory processing and hint that aggressive efforts to treat sleep disturbance early in the course of a pain condition might be beneficial in reducing the severity or impact of clinical pain.     

Possible mechanisms of pain perception in patients with episodic tension-type headache. A new experimental model of myofascial pain

A new experimental human model of myofascial pain using intramuscular infusion of a combination of bradykinin, serotonin (5-hydroxytryptamine), histamine, and prostaglandin E2 was applied to patients with episodic tension-type headache (ETTH) in order to examine pain perception. Fifteen patients with ETTH and 15 healthy controls completed the randomized, balanced, double-blinded, placebo-controlled study. Pain intensity, punctate hyperalgesia and allodynia, and pain quality were recorded. The combination induced a moderate and prolonged pain in both patients (median 51 min) (P = 0.001) and controls (median 22 min) (P = 0.001). Patients reported more pain than controls both after the combination (P = 0.045) and after placebo (P < 0.001). The McGill pain score [PRI(R)] was significantly higher in patients (P = 0.002) and in controls (P = 0.001), whereas pain quality and hyperalgesia were similar after the combination compared with placebo in the two groups. Due to side-effects nine subjects did not complete the study. The increased pain response, but similar qualitative pain perception, in ETTH patients may be explained by sensitization of peripheral nociceptors even though central mechanisms may also be involved.     

Central sensitization phenomena after third molar surgery: A quantitative sensory testing study

Background: Surgical removal of third molars may carry a risk of developing persistent orofacial pain, and central sensitization appears to play an important role in the transition from acute to chronic pain. Aim: The aim of this study was to investigate sensitization (primarily central sensitization) after orofacial trauma using quantitative sensory testing (QST). Methods: A total of 32 healthy men (16 patients and 16 age‐matched control subjects) underwent a battery of quantitative tests adapted to the trigeminal area at baseline and 2, 7, and 30 days following surgical removal of a lower impacted third molar. Results: Central sensitization for at least one week was indicated by significantly increased pain intensity evoked by intraoral repetitive pinprick and electrical stimulation (p<0.05) including facilitation of temporal summation mechanisms (p<0.05), extraoral repetitive electrical stimulation (p<0.001), significantly more frequent aftersensation in patients (p<0.001), extraoral hyperalgesia due to single pinprick stimulation (p<0.05) and larger pain areas due to intranasal stimulation (p<0.001). Peripheral sensitization was indicated by intraoral hyperalgesia due to single pinprick (p<0.05). Conclusion: We found clear signs of sensitization of the trigeminal nociceptive system for at least one week after the surgery. Our results indicate that even a minor orofacial surgical procedure may be sufficient to evoke signs of both central and peripheral sensitization, which may play a role in the transition from acute to chronic pain in susceptible individuals.     

Dose response of tramadol and its combination with paracetamol in UVB induced hyperalgesia

Combining tramadol with paracetamol is an established analgesic treatment strategy. However, dosing and differential effects on peripheral and central hyperalgesia are still to be determined. After Ethics Committee approval, 32 volunteers have been included in this 2 phased, double blinded, placebo controlled, cross‐over study. A defined small skin area was irradiated with a UVB source inducing hyperalgesia. Twenty‐four hours after irradiation, heat pain‐, cold pain threshold (HPPT, CPPT), mechanical pain sensitivity to pin prick (MPS) in the area of pin prick hyperalgesia (AsH) and MPS in the sunburn were determined. In phase I, measurements have been repeated 30 min after receiving cumulative 0.3, 0.6 and 1 mg/kg of intravenous (i.v.) tramadol or active placebo. Only at 1 mg/kg tramadol and solely for MPS in the sunburn a reduction to placebo could be demonstrated (p = 0.024). Accordingly in phase II, the trial has been repeated using 1 mg/kg tramadol and paracetamol or placebo in a cumulative i.v. dose of 330, 660 and 990 mg. Now the addition of 330 mg paracetamol to tramadol reduced thermal hyperalgesia by 1.15 °C (CI 0.55; 1.76). This effect, however, did not increase with higher doses. Tramadol showed week anti‐hyperalgesia reducing CPPT, MPS and AsH compared to baseline measurements (p < 0.05). Paracetamol also reduced secondary hyperalgesia, but no combination effect with tramadol could be shown. We conclude, in inflammatory hyperalgesia tramadol alone exerts only weak anti‐hyperalgesia. Even adding a small dose paracetamol enhances thermal anti‐hyperalgesia.     

Sensitivities to Thermal and Mechanical Stimuli: Adults With Sickle Cell Disease Compared to Healthy,Pain-Free African American Controls

Evidence supports^, but is inconclusive that sensitization contributes to chronic pain in some adults with sickle cell disease (SCD). We determined the prevalence of pain sensitization among adults with SCD pain compared with pain-free healthy adults. In a cross sectional, single session study of 186 African American outpatients with SCD pain (age 18–74 years, 59% female) and 124 healthy age, gender, and race matched control subjects (age 18–69 years, 49% female), we compared responses to standard thermal (Medoc TSA II) and mechanical stimuli (von Frey filaments). Although we observed no significant differences in thermal thresholds between controls and patients, patients with SCD had lower pain thresholds to mechanical stimuli and reported higher pain intensity scores to all thermal and mechanical stimuli at a non-painful body site. Compared with controls, about twice as many patients with SCD showed sensitization: 12% versus 23% at the anterior forearm site (P = .02), and 16% versus 32% across 3 tested sites (P = .004). Among patients with SCD, 18% exhibited some element of central sensitization. Findings indicate that persistent allodynia and hyperalgesia can be part of the SCD pain experience and should be considered when selecting therapies for SCD pain.PerspectiveCompared with matched healthy controls, quantitative sensory testing in adults with pain and sickle cell disease (SCD) demonstrates higher prevalence of sensitization, including central sensitization. The findings of allodynia and hyperalgesia may indicate neuropathic pain and could contribute to a paradigm shift in assessment and treatment of SCD pain.     

Habituation to pain in "medication overuse headache": a CO2 laser-evoked potential study

(Headache 2012;52:792‐807) Objective.— Our aim was to investigate CO₂ laser‐evoked potential (LEP) habituation to experimental pain in a group of patients affected by medication‐overuse headache, with a history of episodic migraine becoming chronic, before and after treatment, consisting in acute medication withdrawal and a preventive treatment cycle. Background.— One of the main features of LEPs in migraineurs is a lower habituation to repetitive noxious stimuli during the interictal phase. Methods.— LEPs were recorded to stimulation of both the right hand and the right perioral region in 14 patients and in 14 healthy subjects. The habituation of both the N1 and the vertex N2/P2 components was assessed by measuring the LEP amplitude changes across 3 consecutive repetitions of 30 trials each. Results.— In the 8 patients who had clinically improved after treatment, the N2/P2 amplitude habituation was significantly higher after treatment than before treatment following both hand (F = 43.2, P < .0001) and face stimulation (F = 6.9, P = .01). In these patients, the N2/P2 amplitude habituation after treatment was not different from that obtained in healthy controls (P = .18 and P = .73 for hand and face stimulation, respectively). On the contrary, in the patients who did not improve, the N2/P2 amplitude still showed reduced habituation after both hand (F = 3.1, P = .08) and face (F = 0.7, P = .4) stimulation. Conclusion.— The deficient habituation of the vertex N2/P2 complex was partly restored after successful treatment of medication‐overuse headache, reflecting a modification in pain‐processing pathways.     

Modulation of sensitized C‐fibers by adrenergic stimulation in human neuropathic pain

The chronic constriction injury model is widely used in studying mechanisms of neuropathic pain. In this model neuropathic pain can be influenced by sympathetic interventions. It is assumed that similar mechanisms as in animals are responsible for pain arising from nerve entrapment syndromes in humans. The aim of the present study was to investigate if in patients with nerve entrapment nociceptive afferents can be modulated by adrenergic stimulation. Methods: Twenty patients with pain due to a unilateral entrapment of the median nerve and 10 controls were included in the study. Spontaneous pain, mechanical and thermal evoked pain were assessed within the innervation territory of the lesioned nerve and the corresponding contralateral segment in patients and on the right hand side in healthy volunteers. The examinations were performed at baseline, during whole body cooling (sympathetic activation) and whole body warming (sympathetic inhibition), and after norepinephrine iontophoresis. Results: All patients reported spontaneous pain. Mechanical allodynia, punctate hyperalgesia and cold allodynia was not found. According to side‐to‐side differences in heat pain thresholds, patients were separated in patients with (n=10) and without (n=10) heat hyperalgesia. Adrenergic stimulation did not induce or enhance spontaneous or mechanical evoked pain in any patient or control subject. However in patients with pre‐existing heat hyperalgesia sympathetic stimulation aggravated heat hyperalgesia significantly. Further in these patients the decrease in heat pain thresholds observed after norepinephrine iontophoresis was significantly higher compared to patients without pre‐existing heat hyperalgesia. Conclusion: Sympathetic–afferent interaction does not play a major role in pain generation due to nerve entrapment. Nevertheless in a subgroup of patients nociceptive afferents show sensitivity to physiological and pharmacological sympathetic stimulation. This finding is important because it emphasises that despite there is no clinical detectable effect on pain sympathetic afferent interaction can be found.     

Investigation of pain sensitivity following 3 nights of disrupted sleep in healthy individuals

Background

Poor quality sleep is a common complaint among people with chronic pain. The co-occurrence of poor sleep quality and chronic pain often comes with increased pain intensity, more disability and a higher cost of healthcare. Poor sleep has been suggested to affect measures of peripheral and central pain mechanisms. To date, sleep provocations are the only models proven to affect measures of central pain mechanisms in healthy subjects. However, there are limited studies investigating the effect of several nights of sleep disruption on measures of central pain mechanisms.

Methods

The current study implemented three nights of sleep disruption with three planned awakenings per night in 30 healthy subjects sleeping at home. Pain testing was conducted at the same time of day at baseline and follow-up for each subject. Pressure pain thresholds were assessed bilaterally on the infraspinatus and gastrocnemius muscles. Using handheld pressure algometry, suprathreshold pressure pain sensitivity and area were also investigated on the dominant infraspinatus muscle. Cuff-pressure pain detection and tolerance thresholds, temporal summation of pain and conditioned pain modulation were investigated using cuff-pressure algometry.

Results

Temporal summation of pain was significantly facilitated (p = 0.022), suprathreshold pain areas (p = 0.005) and intensities (p < 0.05) were significantly increased, and all pressure pain thresholds were decreased (p < 0.005) after sleep disruption compared to baseline.

Conclusions

The current study found that three consecutive nights of sleep disruption at home induced pressure hyperalgesia and increased measures of pain facilitation in healthy subjects, which is consistent with previous findings.

Significance

Poor quality of sleep is often experienced by patients with chronic pain, with the most common complaint being nightly awakenings. This exploratory study is the first to investigate changes in measures of central and peripheral pain sensitivity in healthy subjects after sleep disruptions for three consecutive nights without any restrictions on total sleep time. The findings suggest that disruptions to sleep continuity in healthy individuals can induce increased sensitivity to measures of central and peripheral pain sensitization.     

Comparing Central Pain Processing in Individuals With Non-Traumatic Neck Pain and Healthy Individuals: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis examined the evidence for altered central pain processing in people with nontraumatic neck pain and the relationship among central pain processing, demographics, and pain-related characteristics. Case-control studies reporting measures of altered central pain processing using quantitative sensory testing were reviewed. Standardized mean differences (SMDs) and 95% confidence intervals between people with nontraumatic neck pain and controls were calculated. Meta-analysis was performed using random-effects models when appropriate. Associations between SMDs with demographics and pain-related characteristics were explored on a study level using metaregression. Twenty-six studies were eligible with 25 included for meta-analysis. Meta-analysis demonstrated mechanical hyperalgesia at remote nonpainful sites in the full sample (sample size [n] = 1305, SMD = −0.68) and in the subgroup with moderate/severe disability (n = 165, SMD = −0.86; moderate-quality evidence). Metaregression indicated that remote mechanical hyperalgesia was negatively associated with age (R² = 25.4%, P = 0.031). Very low- to low-quality evidence of remote cold and heat hyperalgesia and dysfunctional conditioned pain modulation were identified. This review suggests that altered central pain processing is present in people with nontraumatic neck pain and may be associated with disability levels and age.PerspectiveThis review found moderate-quality evidence of mechanical hyperalgesia at remote nonpainful sites in patients with nontraumatic neck pain compared with controls, indicating altered central pain processing. However, more studies are needed to confirm findings from dynamic quantitative sensory testing.     

Attentional modulation fails to attenuate the subjective pain experience in chronic,unexplained pain

Background: Chronic, unexplained pain is a common, ill‐understood clinical problem. Increased sensitivity for pain and other stimuli is often implied as an underlying mechanism. Attentional processes influence central pain processing and might mediate hypersensitivity at a cerebral level. Aims: To study patients with chronic, unexplained pain with respect to (a) subjective pain experience; (b) effects of attentional manipulation; (c) level at which alterations in pain processing occur: locally (symptomatic body region), or generalised. Methods: We compared 16 patients with chronic, unexplained limb pain with 16 matched healthy controls. Pain thresholds to electrical stimuli were recorded. Subjects then received individually thresholded painful and non‐painful stimuli, with manipulation of attention towards or away from pain. The intensity of pain perception was recorded by means of visual analogue scales (VAS). Pain thresholds and effects of Attention and Laterality on VAS scores were compared between groups by means of general linear modelling (restricted to 12 patients with unilateral pain and 12 controls). Results: Distraction increased thresholds for pain in healthy volunteers, but this effect was significantly attenuated in patients. Significant interactions between attention‐effects, stimulus laterality and stimulus intensity indicated that VAS scores for painful stimuli were attenuated during distraction in healthy controls, but not in pain patients. Conclusions: Results support the notion that pain processing is enhanced in chronic, unexplained pain, and that the influence of attentional modulation on pain processing is attenuated. Potential cerebral mechanisms are changes in either attentional allocation or attention‐mediated descending pain modulation. The changes seem to occur at a generalised level.     

Quality of life in subgroups of individuals with whiplash associated disorders

Background: The term whiplash associated disorders (WAD) includes a wide range of complaints, with neck pain as predominating symptom. Living with long term pain influences quality of life. In previous studies of other chronic pain patients, subgrouping has been made according to thermal pain thresholds measured in quantitative sensory testing (QST). Aims: The aims of the present study are threefold, (1) to evaluate thermal pain thresholds and health related quality of life in WAD patients compared to healthy pain‐free individuals, (2) to explore whether subgrouping of the WAD patients is possible according to thermal pain thresholds over trapezius, and if so (3) to explore differences between the subgroups. Methods: Twenty‐six patients with WAD and 18 healthy pain‐free controls took part in the study. Thermal pain thresholds were measured in two sites (over the thenar and the trapezius muscle) using quantitative sensory testing (QST). Health related quality of life (HRQoL) was assessed using the SF‐36. The visual analogue scale was used to rate pain intensity and unpleasantness related to the experimental situation. Results: WAD patients are more sensitive to thermal pain, and scored lower on the SF‐36 in all scales when compared with healthy pain‐free individuals. After analyzing clusters (K‐means algorithm) two subgroups of WAD emerge, pain insensitive and pain sensitive. The pain insensitive group differed significantly from the pain sensitive group in the Role Emotional subscale of SF‐36 (p=0.025). Conclusions: Thermal pain hyperalgesia, especially for cold, seems to be a determinant for subgrouping WAD patients. These results support that such a classification of a heterogenous group could be of importance in tailoring treatment and early interventions.     

Bilateral widespread mechanical pain hypersensitivity as sign of central sensitization in patients with cluster headache

Objective.— To investigate bilateral widespread pressure pain hyperalgesia in deep tissues over symptomatic (trigemino‐cervical) and nonsymptomatic (distant pain‐free) regions in patients with cluster headache (CH). Background.— Central sensitization is claimed to play a relevant role in CH. No study has previously searched for widespread pressure hyperalgesia in deep tissues over both symptomatic (trigemino‐cervical) and nonsymptomatic (distant pain‐free) regions in patients with CH. Methods.— Sixteen men (mean age: 43 ± 11 years) with CH in a remission phase and 16 matched controls were recruited. Pressure pain thresholds (PPTs) were bilaterally measured over the supra‐orbital (V1), infra‐orbital (V2), mental (V3), median (C5), radial (C6), and ulnar (C7) nerves, C5‐C6 zygapophyseal joint, mastoid process, and tibialis anterior muscle by an assessor blinded to the subjects' condition. Results.— The results showed that PPT levels were significantly decreased bilaterally in patients with CH as compared with healthy controls (all sites, P < .001). A greater degree of sensitization over the mastoid process (P < .001) and a lower degree of sensitization over the tibialis anterior muscle (P < .01) was found. Conclusions.— Our findings revealed bilateral widespread pressure pain hypersensitivity in patients with CH confirming the presence of central sensitization mechanisms in this headache condition.     

Effects of an Extract of Salmon Milt on Symptoms and Serum TNF and Substance P in Patients With Fibromyalgia Syndrome

PurposeThe aim of this study was to evaluate the effects of a dietary supplement containing primarily an extract of salmon's milt (semen) on symptoms and blood levels of proinflammatory molecules in patients with fibromyalgia syndrome (FMS), a chronic, painful musculoskeletal disease without a distinct pathogenesis or treatment. We recently reported increased serum levels of the proinflammatory molecules substance P (SP) and tumor necrosis factor (TNF) in patients with FMS as compared to those in normal controls.MethodsThis prospective, open-label study was conducted in patients with FMS (n = 87; 80 women, 7 men; age range, 18–80 years) selected from 2 clinical centers in Spain. Patients were administered the supplement and were evaluated at weeks 1 (before treatment), 4, 8, and 12 (end of treatment) for clinical parameters of functioning, fatigue, and pain, as well as overall impression. Patients were directed to take 1 capsule per day in the morning for the first 4 weeks, followed by 1 capsule in the morning and 1 capsule in the evening for the remaining 8 weeks. Differences in symptom scores in patients with FMS between weeks 1 and weeks 4, 8, and 12 were evaluated using ANOVA. Blood was obtained and serum separated in patients with FMS at 1 and 12 weeks and in a separate population of healthy controls (n = 20; 15 women, 5 men; age range, 25–65 years). Serum levels of SP and TNF were measured in patients with FMS at 1 and 12 weeks and in healthy controls by ELISA. TNF and SP levels in patients with FMS were compared between weeks 1 and 12, as well as between patients with FMS and untreated controls, using the Mann–Whitney U test.FindingsClinical parameters of functioning, fatigue, and pain, as well as overall impression, were improved significantly at 4 weeks as compared to 1 week and remained unchanged for the duration of the study (all, P < 0.0001). Serum TNF and SP levels were significantly elevated at 1 week in patients with FMS compared to controls and were decreased significantly at 12 weeks as compared to 1 week (all, P < 0.0001).ImplicationsOur findings indicate that this dietary supplement may significantly improve symptoms in patients with FMS. This is the first time to our knowledge that any molecule has been reported to be associated with a reduction in serum SP level. Consequently, the supplement or its hypothesized main active ingredient, spermine, may be developed as a novel treatment approach to FMS or other neuroinflammatory conditions. ClinicalTrials.gov identifier: NCT03911882.