Interaction of calcitonin gene related peptide (CGRP) and substance P (SP) in human skin

Calcitonin gene related peptide (CGRP) and substance P (SP) are neuropeptides that are simultaneously released from nociceptive C-fibers. CGRP is a potent vasodilator, inducing a long-lasting increase in superficial skin blood flow, whereas SP induces only a brief vasodilation but a significant plasma extravasation. CGRP and SP may play important roles in the pathophysiology of various pain states but little is known about their interaction.Different concentrations of SP (ranging from 10^− 5 M to 10^− 9 M) were applied to the volar forearm of 24 healthy subjects via dermal microdialysis. SP was applied either alone or in combination with CGRP10^− 9 M and CGRP 10^− 6 M.As expected, SP induced a transient increase in skin blood flow that decayed shortly after application. This transient blood flow peak was blunted with co-application of CGRP 10^− 9 M and inhibited with co-application of CGRP10^− 6 M. SP alone induced plasma protein extravasation (PPE). However, when CGRP10^− 6 M was added, the PPE significantly increased.Our results demonstrate a complex interaction of the neuropeptides CGRP and SP. CGRP10^− 6 M prevented SP-induced early vasodilation but augmented SP-induced PPE. These interactions might explain why vascular symptoms in chronic pain can differ strikingly between individuals.     

Calcitonin-gene related peptide and cerebral vasospasm

The pathophysiology of arterial vasospasm following subarachnoid hemorrhage (SAH) is poorly understood and the contribution of endogenous neuropeptides has not been sufficiently elucidated. Recently, we detected an excessive release of vasoconstrictive neuropeptide Y (NPY) in SAH patients and identified a significant correlation of NPY cerebrospinal fluid (CSF) levels with vasospasm-related ischemia. Here, we present the results of an experimental study on the possible role of the potent endogenous vasodilator calcitonin-gene related peptide (CGRP) in the acute stage of SAH. Twelve consecutive patients with SAH were included. Seven patients had severe arterial vasospasm, confirmed by transcranial doppler-sonography (TCD). Prospectively, CSF was collected from day 1 to day 10 after onset of the SAH. The levels of CGRP were determined in a competitive enzyme immunoassay and were correlated with the clinical course and hemodynamic changes. A cohort of 29 patients without CNS disease served as a control. CGRP was significantly higher in SAH patients compared with the control group (p < 0.05). From day 1 to day 4, the CGRP levels in patients without vasospasm were significantly higher than the levels of CGRP in patients with vasospasm (p < 0.05). These patients did not develop cerebral ischemia. The significantly increased levels of the CGRP during the first days after onset of the SAH in the non-vasospasm group indicate a potential protective role of CGRP. CGRP may alleviate arterial vasoconstriction and thus protect the brain from vasospasm and subsequent ischemia.     

Effects of short-term acetaminophen and celecoxib treatment on orthodontic tooth movement and neuronal activation in rat

Non-steroidal anti-inflammatory drugs (NSAIDs) have been used for pain relief in orthodontics, but clinical studies reported that they may reduce tooth movement (TM). By other side, TM seems to activate brain structures related to nociception, but the effects of NSAIDs in this activation have not been studied yet. We analyzed the effect of short-term treatment with acetaminophen or celecoxib in the separation of rat upper incisors, as well as in neuronal activation of the spinal trigeminal nucleus, following tooth movement. Thirty rats (400–420 g) were pretreated through oral gavage (1 ml/dose) with acetaminophen (200 mg/kg), celecoxib (50 mg/kg) or vehicle (carboxymethylcellulose 0.4%). After 30 min, they received an activated (30 g) orthodontic appliance for TM. In controls, this appliance was immediately removed after its introduction. Rats received ground food, and every 12 h, one of the drugs or vehicle. After 48 h, they were anesthetized, maxilla was radiographed, and were perfused with 4% paraformaldehyde. Brains were further processed for Fos immunohistochemistry. TM induced incisor distalization (p < 0.05) and neuronal activation of the spinal trigeminal nucleus. Treatment with both drugs did not affect tooth movement, but reduced c-fos expression in the caudalis subnucleus. No changes in c-fos expression were seen in the oralis and interpolaris subnuclei. We conclude that neither celecoxib nor acetaminophen seems to affect tooth movement, when used for 2 days, but both drugs are able to reduce the activation of brain structures related to nociception. Short-term treatment with celecoxib, thus, may be a therapeutic alternative to acetaminophen when the latter is contraindicated.     

The association between periodontal disease and seizure severity in refractory epilepsy patients

PurposePeriodontal diseases are common in most populations and affect people at all socioeconomic levels. Evidence suggests that patients with epilepsy actually have higher risks of dental disease and increased oral health needs, but the frequency and consequences of poor controlled seizures on dental and periodontal health have not been reported before. We aimed to assess the impact of seizure frequency on periodontal status and oral hygiene in a sample of epilepsy patients.MethodsOne hundred and nine consecutive patients treated for epilepsy at the outpatient clinic of our University Hospital were invited to take part in an oral examination to determine their periodontal disease status, together with a control group. In addition, seizure frequency and use of medication were documented.ResultsIn logistic regression model, patients were significantly more susceptible to bad oral hygiene, gingivitis and periodontitis that controls (p < 0.001); seizure frequency was significantly related to bad oral hygiene (p = 0.010), gingivitis (p < 0.001) and periodontitis (p < 0.001). Tooth brushing habits and presence of caries were associated with oral health in patients group.ConclusionOur study found a significant positive correlation between periodontal disease and seizure severity. Epilepsy patients need to focus more on their oral health and quality of oral hygiene.     

Experimental colitis triggers the release of substance P and calcitonin gene-related peptide in the urinary bladder via TRPV1 signaling pathways

Clinical data provide evidence of high level of co-morbidity among genitourinary and gastrointestinal disorders characterized by chronic pelvic pain. The objective of this study was to test the hypothesis that colonic inflammation can impact the function of the urinary bladder via activation of TRPV1 signaling pathways followed by alterations in gene and protein expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in sensory neurons and in the bladder. Inflammation was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS, 12.5 mg/kg), and desensitization of TRPV1 receptors was evoked by intracolonic resiniferatoxin (RTX, 10^?7 M). mRNA and protein concentrations of CGRP and SP were measured at 3, 5 and 30 days. RTX instillation in the colon caused 3-fold up-regulation of SP mRNA in the urinary bladder at day 5 (n = 7, p ≤ 0.05) followed by 35-fold increase at day 30 (n = 5, p ≤ 0.05). Likewise, TNBS colitis triggered 15.8-fold up-regulation of SP mRNA 1 month after TNBS (n = 5, p ≤ 0.05). Desensitization of colonic TRPV1 receptors prior to TNBS abolished SP increase in the urinary bladder. RTX led to 4.3-fold increase of CGRP mRNA at day 5 (n = 7, p ≤ 0.05 to control) in the bladder followed by 28-fold increase at day 30 post-RTX (n = 4, p ≤ 0.05). Colitis did not alter CGRP concentration during acute phase; however, at day 30 mRNA level was increased by 17.8 ± 6.9-fold (n = 5, p ≤ 0.05) in parallel with 4-fold increase in CGRP protein (n = 5, p ≤ 0.01) in the detrusor. Protein concentration of CGRP in the spinal cord was diminished by 45–65% (p ≤ 0.05) during colitis. RTX pretreatment did not affect CGRP concentration in the urinary bladder; however, it caused a reduction in CGRP release from lumbosacral DRG neurons during acute phase (3 and 5 days post-TNBS). Our results clearly demonstrate that colonic inflammation triggers the release of pro-inflammatory neuropeptides SP and CGRP in the urinary bladder via activation of TRPV1 signaling mechanisms enunciating the neurogenic nature of pelvic organ cross-sensitization.     

Cannabinoid receptor CB1-immunoreactive nerve fibres in painful and non-painful human tooth pulp

The cannabinoid receptor CB1 is involved in modulation of neuronal hypersensitivity and pain. The aim of this study was to evaluate CB1 receptor levels for the first time in dental pain. A total of 19 patients due for molar extraction were divided into two groups, those with existing dental pain (n = 9), and those with no history of pain (n = 10). Immunohistochemistry and computer image analysis was used to evaluate CB1-positive nerve fibres in tooth pulp, with neurofilament-immunostaining as a structural nerve marker. CB1-immunoreactive nerve fibres were scattered throughout the tooth pulp and often seen in nerve bundles, but the fibres did not penetrate the subodontoblastic layer. There was no statistically significant change in the CB1 nerve fibre percentage area in the painful group compared to the non-painful group (p = 0.146); the neurofilament fibres were significantly reduced in the painful group compared to the controls (p = 0.028), but there was no difference in the ratio of CB1 to neurofilaments between the two groups. Thus, CB1 expression is maintained by nerve fibres in painful human dental pulp, and peripherally-restricted CB1 agonists currently in development may advance the treatment of dental pain.     

Thermal application modulates orofacial somatosensory perception in healthy men and women

ObjectiveTo test if orofacial somatosensory perception can be modulated by experimental thermal application in healthy human.MethodsTwelve men and twelve age-matched women participated. In each session thermal application with 10, 42 or 32 °C (cooling, warming, control) was applied to the skin over the right masseter using a thermode. Quantitative sensory testing was performed at the skin over the right (testing side) and left (contralateral side) masseter before, during, after the thermal application.ResultsDuring the cooling, mechanical detection threshold (MDT), mechanical pain threshold (MPT) and pressure pain threshold (PPT) were increased, and mechanical pain sensitivity was decreased at testing side compared with baseline (P < 0.005). The MPT and PPT at the contralateral side were also increased (P < 0.004). During the warming and control, the MDT was increased at the testing side compared with baseline (P = 0.002). The somatosensory sensitivity was decreased during cooling compared to warming and control (P < 0.05). No gender differences were found.ConclusionsThis study shows an ipsilateral decrease of cutaneous sensation or pain sensitivity during cooling without gender differences. In addition, hypoalgesia on the contralateral side suggests a central mode of action.SignificanceThe results support clinical experiences that cooling may alleviates pain both locally and generally.     

Sensorimotor interaction between somatosensory painful stimuli and motor sequences affects both anticipatory alpha rhythms and behavior as a function of the event side

It has been shown that concomitant painful stimulation and simple movement at the same hand is related to decreased anticipatory alpha event-related desynchronization (ERD) and reduced pain intensity, possibly due to the interference between somatosensory and motor information processing (Babiloni et al. [6]). Here, we tested the hypothesis that such interference also affects motor performance during sequential movements. Visual warning stimuli were followed by imperative stimuli associated to electrical painful stimulation at left or right middle finger; imperative stimuli triggered motor sequences with right index finger. Electroencephalographic data (N = 10, 128 electrodes) were spatially enhanced by surface Laplacian transformation. Cortical activity as revealed by the alpha event-related desynchronization (ERD) was compared in “Pain + ipsilateral movement” condition (movements and painful stimuli performed at the right hand) vs. “Pain + contralateral movement” condition (painful stimuli at left hand and movements performed at the right hand). Results showed that compared with the “Pain + contralateral movement” condition, the “Pain + ipsilateral movement” condition induced lower anticipatory alpha ERD (about 10–12 Hz) in left sensorimotor area, lower subjective pain rate, and delayed movement initiation at the group level. These findings suggest that anticipatory alpha rhythms may underlie cortical preparatory sensorimotor processes preceding somatosensory painful and the initiation of sequential motor events occurring at unilateral or bilateral hand.     

Mechanisms operated by endothelin ETA and ETB receptors in the trigeminal ganglion contribute to orofacial thermal hyperalgesia induced by infraorbital nerve constriction in rats

Endothelins, acting through specific endothelin ET_A and/or ET_B receptors, participate in nociceptive processing in models of cancer, inflammatory and neuropathic pain. The present study investigated which cell types express endothelin receptors in the trigeminal ganglion, and the contribution of mechanisms mediated by endothelin ET_A and ET_B receptors to orofacial heat hyperalgesia induced by unilateral constriction of the infraorbital nerve (CION). Both receptor types were identified by immunohistochemistry in the trigeminal ganglion, ET_A receptors on small-sized non-myelinated and myelinated A-fibers and ET_B receptors on both satellite glial cells and small-sized non-myelinated neuronal cells. CION promoted ipsilateral orofacial heat hyperalgesia which lasted from Day 2 until Day 10 after surgery. Ongoing CION-induced heat hyperalgesia (on Day 4) was reduced transiently, but significantly, by systemic or local treatment with antagonists of endothelin ET_A receptors (atrasentan, 10 mg/kg, i.v.; or BQ-123, 10 nmol/lip), endothelin ET_B receptors (A-192621, 20 mg/kg, i.v.; or BQ-788, 10 nmol/ lip), or of both ET_A/ET_B receptors (bosentan, 10 mg/kg, i.v.; or BQ-123 plus BQ-788, each at 10 nmol/lip). On the other hand, CION-induced heat hyperalgesia was transiently abolished over the first 90 min following i.p. injection of morphine hydrochloride (2.5 mg/kg), but fully resistant to reversal by indomethacin (4 mg/kg, i.p.) or celecoxib (10 mg/kg, i.p.). Thus, heat hyperalgesia induced by CION is maintained, in part, by peripheral signaling mechanisms operated by ET_A and ET_B receptors. Endothelin receptors might represent promising therapeutic targets for the control of trigeminal neuropathic pain.     

Modality and sex differences in pain sensitivity during human endotoxemia

Systemic inflammation can induce pain hypersensitivity in animal and human experimental models, and has been proposed to be central in clinical pain conditions. Women are overrepresented in many chronic pain conditions, but experimental studies on sex differences in pain regulation during systemic inflammation are still scarce. In two randomized and double blind placebo controlled experiments, we used low doses of lipopolysaccharide (LPS) as an experimental model of systemic inflammation. The first study employed 0.8 ng/kg LPS in a within-subject design of 8 individuals (1 woman), and the second study 0.6 ng/kg LPS in a between-subject design of 52 participants (29 women). We investigated the effect on (a) pressure, heat, and cold pain thresholds, (b) suprathreshold noxious heat and cold sensitivity, and (c) conditioned pain modulation (CPM), and differences between men and women. LPS induced significantly lower pressure pain thresholds as compared to placebo (mean change with the 0.8 ng/kg dose being −64 ± 30 kPa P = .04; with the 0.6 ng/kg dose −58 ± 55 kPa, P < .01, compared to before injection), whereas heat and cold pain thresholds remained unaffected (P’s > .70). Suprathreshold noxious pain was not affected by LPS in men (P’s ⩾ .15). However, LPS made women rated suprathreshold noxious heat stimuli as more painful (P = .01), and showed a tendency to rate noxious cold pain as more painful (P = .06) as compared to placebo. Furthermore, LPS impaired conditioned pain modulation, a measure of endogenous pain inhibition, but this effect was also restricted to women (P < .01, for men P = .27). Pain sensitivity correlated positively with plasma IL-6 and IL-8 levels. The results show that inflammation more strongly affects deep pain, rather than cutaneous pain, and suggest that women’s pain perception and modulation is more sensitive to immune activation than men’s.     

Spinal neuropeptide modulation,functional assessment and cartilage lesions in a monosodium iodoacetate rat model of osteoarthritis

Background and aimsCharacterising the temporal evolution of changes observed in pain functional assessment, spinal neuropeptides and cartilage lesions of the joint after chemical osteoarthritis (OA) induction in rats.Methods and resultsOn day (D) 0, OA was induced by an IA injection of monosodium iodoacetate (MIA). Rats receiving 2 mg MIA were temporally assessed at D3, D7, D14 and D21 for the total spinal cord concentration of substance P (SP), calcitonin gene related-peptide (CGRP), bradykinin (BK) and somatostatin (STT), and for severity of cartilage lesions. At D21, the same outcomes were compared with the IA 1 mg MIA, IA 2 mg MIA associated with punctual IA injection of lidocaine at D7, D14 and D21, sham (sterile saline) and naïve groups. Tactile allodynia was sequentially assessed using a von Frey anaesthesiometer. Non-parametric and mixed models were applied for statistical analysis. Tactile allodynia developed in the 2 mg MIA group as soon as D3 and was maintained up to D21. Punctual IA treatment with lidocaine counteracted it at D7 and D14. Compared to naïve, [STT], [BK] and [CGRP] reached a maximum as early as D7, which plateaued up to D21. For [SP], the increase was delayed up to D14 and maintained at D21. No difference in levels of neuropeptides was observed between MIA doses, except for higher [STT] in the 2 mg MIA group (P = 0.029). Neuropeptides SP and BK were responsive to lidocaine treatment. The increase in severity of cartilage lesions was significant only in the 2 mg MIA groups (P = 0.01).ConclusionIn the MIA OA pain model, neuropeptide modulation appears early, and confirms the central nervous system to be an attractive target for OA pain quantification. The relationship of neuropeptide release with severity of cartilage lesions and functional assessment are promising and need further validation.     

Critical role of myofascial reeducation in pediatric sleep-disordered breathing

BackgroundLimited studies suggest that pubertal development may lead to a recurrence of sleep-disordered breathing (SDB) despite previous curative surgery. Our study evaluates the impact of myofunctional reeducation in children with SDB referred for adenotonsillectomy, orthodontia, and myofunctional treatment in three different geographic areas.MethodsA retrospective investigation of children with polysomnographic analysis following adenotonsillectomy were referred for orthodontic treatment and were considered for myofunctional therapy. Clinical information was obtained during pediatric and orthodontic follow-up. Polysomnography (PSG) at the time of diagnosis, following adenotonsillectomy, and at long-term follow-up, were compared. The PSG obtained at long-term follow-up was scored by a single-blinded investigator.ResultsComplete charts providing the necessary medical information for long-term follow-up were limited. A subgroup of 24 subjects (14 boys) with normal PSG following adenotonsillectomy and orthodontia were referred for myofunctional therapy, with only 11 subjects receiving treatment. Follow-up evaluation was performed between the 22nd and 50th month after termination of myofunctional reeducation or orthodontic treatment if reeducation was not received. Thirteen out of 24 subjects who did not receive myofunctional reeducation developed recurrence of symptoms with a mean apnea–hypopnea index (AHI) = 5.3 ± 1.5 and mean minimum oxygen saturation = 91 ± 1.8%. All 11 subjects who completed myofunctional reeducation for 24 months revealed healthy results.ConclusionDespite experimental and orthodontic data supporting the connection between orofacial muscle activity and oropharyngeal development as well as the demonstration of abnormal muscle contraction of upper airway muscles during sleep in patients with SDB, myofunctional therapy rarely is considered in the treatment of pediatric SDB. Absence of myofascial treatment is associated with a recurrence of SDB.     

Interactions of glutamate and capsaicin-evoked muscle pain on jaw motor functions of men

ObjectiveThe aim of the study was to investigate the interaction between glutamate and capsaicin-evoked muscle pain on human jaw motor functions.MethodsFifteen male volunteers participated. Glutamate or capsaicin or isotonic saline, in a paired-sequence order, was injected randomly into the right or left masseter muscle. Two injections were given in a double-blinded design 25 min apart in one session/week over four weeks: isotonic saline (A1) followed by glutamate (A2), capsaicin (B1) followed by glutamate (B2), isotonic saline (C1) followed by capsaicin (C2), and glutamate (D1) followed by capsaicin (D2). The resting electromyographic (EMG) activity of the right and left masseter muscles, maximum voluntary bite force (MVBF), and maximum voluntary jaw opening (MVJO) were recorded before and after injection and subsequently at 5-min intervals for 50 min. The pain intensity was recorded on a 0–10 numerical rating scale during each MVBF or MVJO jaw function.ResultsResting EMG activity was significantly increased after 5 min of D2 (ANOVA: P = 0.028) injection. The percentage change (compared with baseline) in EMG activity was significantly different between D2 (116.1 ± 6.1%) and C2 (102.1 ± 3.4%) injections (paired t-test: P = 0.039). The MVBF and MVJO were significantly decreased after injection of glutamate or capsaicin, however, there was no significant difference in the relative decrease between A2 and B2, or between C2 and D2 at any time point (P > 0.152). There was a significantly higher peak pain rating after D2 compared to C2 during MVBF or MVJO (P < 0.022), whereas no significant difference in peak pain ratings was found between A2 and B2 (P > 0.084). There were significant negative correlations between pain ratings and MVBF or MVJO (Pearson correlation: P < 0.001).ConclusionsThe results indicate that intramuscular administration of glutamate and capsaicin induces muscle pain which has the potential to perturb some normal jaw motor functions.SignificanceThe present findings suggest that peripheral glutamate and capsaicin receptor mechanisms interact to affect some jaw motor as well as sensory (i.e. pain) functions and provide new insights into the complexity of orofacial pain. Management approaches that target the peripheral nervous system and receptor mechanisms may prevent such changes in jaw motor function.     

Drowsiness and motor responses to consecutive daily doses of promethazine and loratadine

ObjectivesLimited information is available regarding sedation and motor function following repeat dosing of antihistamines. This study examined how promethazine and loratadine affect day-time drowsiness, the commencement of voluntary movement, and involuntary movement when administered on consecutive days.MethodsTen healthy young subjects (24 ± 5 years) were recruited into a double-blind, placebo-controlled, three-way crossover study. Subjects ingested either promethazine, loratadine or a placebo, and ingested the same drug 24 h later. Measures of drowsiness, simple reaction time (SRT), choice reaction time (CRT), and postural tremor were obtained pre-ingestion, 1 h post-ingestion and 2 h post-ingestion on each day.ResultsConsecutive daily doses of promethazine and loratadine affected SRT and CRT, respectively, whereby reaction time deficits were less pronounced following the repeat dose. A reduced tremor response was also observed following consecutive daily dosing of promethazine, in contrast to loratadine which caused an increase in tremor amplitude with the consecutive daily dose.ConclusionsReaction time and tremor responses differed following the single dose compared to consecutive doses.SignificanceSufferers of allergic rhinitis often require antihistamine dosing regimens that continue over multiple days. Future studies will benefit from examining drowsiness and movement responses following single doses as well as consecutive dosing.     

Phenobarbital withdrawal seizures may occur over several weeks before remitting: Human data and hypothetical mechanism

This case is the first report of a patient who had phenobarbital (PB) withdrawal seizures after having been seizure-free for 3 years following temporal lobe surgery. The patient had been taking PB for 14 years when a gradual taper of PB was started. When PB was at 60 mg/d, a titration of lamotrigine (LTG) was started. However, typical complex seizures occurred when the patient was on PB 60 mg/d, along with LTG 25 mg/d. PB was increased back to 90 mg/d and levetiracetam (LEV) was titrated. Seizures appeared when the patient was on PB 30 mg/d and LEV 750 mg BID and continued for 3 weeks after PB was stopped and the patient was on LEV 1000 mg BID. For the following 6 months, her aura frequency remained elevated in comparison to her baseline aura of two auras per month for the previous year before the start of the PB taper. She was followed for 24 months after her last PB withdrawal seizure. During the last 8 months, her aura frequency returned to her baseline. As suggested by animal studies, the PB withdrawal seizures and increase in aura frequency in this patient may be explained by changes in her levels of GABA_A receptor subunits.     

Lack of insula reactivity to aversive stimuli in schizophrenia

Patients with schizophrenia may have altered pain perception, as suggested by clinical reports of pain insensitivity, and recent neuroimaging findings. Here, we examined neural responses to an aversive electrical stimulus and the immediate anticipation of such a stimulus using fMRI and a classical conditioning paradigm, which involved pairing an electrical shock with a neutral photograph. Fifteen men with schizophrenia and 13 healthy men, matched for demographic characteristics, electrical stimulation level and scan movement, were studied. The shock induced robust responses in midbrain, thalamus, cingulate gyrus, insula and somatosensory cortex in both groups. However, compared to controls, the schizophrenic patients displayed significantly lower activation of the middle insula (p_FWE = 0.002, T = 5.72, cluster size = 24 voxels). Moreover, the lack of insula reactivity in the schizophrenia group was predicted by the magnitude of positive symptoms (r = ? 0.46, p = 0.04). In contrast, there were no significant differences between the two groups in the magnitude of neural responses during anticipation of the shock. These findings provide support for the existence of a basic deficit in interoceptive perception in schizophrenia, which could play a role in the generation and/or maintenance of psychotic states.     

Kinematic movement strategies in primary school children with 22q11.2 Deletion Syndrome compared to age- and IQ-matched controls during visuo-manual tracking

The present study focused on the mechanism subserving the production of kinematic patterns in 21 children with 22q11.2DS (mean age = 9.6 ± 1.9; mean FSIQ = 73.05 ± 10.2) and 21 age- and IQ-matched control children (mean age = 9.6 ± 1.9; mean FSIQ = 73.38 ± 12.0) when performing a visuo-manual tracking task in which they had to track a cursor rhythmically between 2 target zones. Children with 22q11.2DS moved faster (overall) and reached their maximum velocity sooner when compared to controls. However, the number of corrective submovements to attain the target did not differ. Children with 22q11.2DS seem to adopt a young ballistic movement strategy, with a fast ballistic first movement phase, followed by a second movement phase with very little online corrections to attain the target. Children with 22q11.2DS are not able to process the incoming feedback during the second movement phase to maximize the accuracy of the ongoing movement and use this phase to prepare the following. The fact that the parietal cortex and cerebellum are involved in action prediction and internal representation and are implicated in children with 22q11.2DS provides a possible neurological basis for their problems with prospective control and tracking behavior.     

Tolérance à la détresse et expérience de la douleur chronique

IntroductionChronic pain is a highly prevalent condition that is associated with distressing somatic and emotional experiences. Consequently, an individual's distress tolerance, the perceived capacity to tolerate negative psychological and physical states, may influence their pain experience. This effect could be explained in part by a reduction in the catastrophic interpretation of pain which is associated with increased pain intensity and interference in everyday activities.AimsThe first aim of this study was to explore the association between the components of the 5-factor model of distress tolerance and (1) pain intensity and (2) pain interference in everyday activities. The secondary aim was to assess the potential mediating effect of pain catastrophizing in the eventual association between components of distress tolerance and (1) pain intensity or (2) pain interference in everyday activities.MethodThis is a cross-sectional study of adult (18 years or older) university students and staff with chronic pain (3 months). They were invited to complete the online questionnaire through an email invitation. Pain intensity and interference in everyday functioning were assessed with the corresponding subscales of the Brief Pain Inventory. The following instruments were used to assess the components of the 5-factor model of distress tolerance: Ambiguity Tolerance Scale (tolerance to ambiguity), Intolerance to Uncertainty Scale (reversed score: tolerance to uncertainty), Discomfort Intolerance Scale (reversed score: discomfort tolerance), Distress Tolerance Scale (tolerance to negative emotions), Frustration Discomfort Scale (tolerance to frustration). Participants also completed the Pain Catastrophizing Scale.ResultsEighty participants were recruited (57 % women, mean age = 33.09; standard deviation = 12,87). Tolerance to negative emotions was the only component of distress tolerance that was associated with pain (ß = ?0.04; 95% CI): ?0.07–?0.01; t (78) = ?3.06, p < 0.01) or pain interference in everyday functioning (ß = ?0.07; 95% CI: ?0.10–?0.03; t (78) = ?3.97, p < 0.01), independently of the others. Combined with age, these factors explained 16.2 % of the variance in pain intensity and 19.4 % of the variance in pain interference. Pain catastrophizing partially mediated the association between tolerance to negative emotions and pain interference in everyday functioning, but it was not involved in the association between tolerance to negative emotions and pain intensity.ConclusionTolerance to negative emotions appears to be the most relevant aspect of distress tolerance in the context of chronic pain and is a potential clinical target that is independent and complementary from pain catastrophizing.     

The pain-induced change in relative activation of upper trapezius muscle regions is independent of the site of noxious stimulation

ObjectiveTo assess the effect of local excitation of nociceptors at different locations of the upper trapezius muscle on the spatial distribution of upper trapezius electromyographic (EMG) amplitude during sustained contraction.MethodsSurface (EMG) signals were recorded from the upper trapezius muscle with a grid of 10 × 5 electrodes from nine healthy men during 90° shoulder abduction sustained for 60 s. In one experimental session, the subjects received separate injections of 0.4 ml of hypertonic saline (experimental muscle pain) into the cranial and caudal region of the upper trapezius. In a separate experimental session the same subjects received two injections of 0.2 ml each of hypertonic saline simultaneously in the cranial and caudal region. The EMG root mean square (RMS) values were computed for each electrode location to provide a topographical map of EMG amplitude.ResultsThe RMS value averaged across all electrode locations decreased following injection of hypertonic saline (P < 0.05) by a similar amount for the two experimental sessions. The pain-induced decrease was larger in the cranial than in the caudal region for both experimental sessions, as evidenced by a shift of the EMG amplitude distribution towards the caudal region of the muscle (P < 0.0001).ConclusionMuscle pain induces a consistent change in the spatial activation of the upper trapezius muscle which is independent of the site of noxious stimulation.SignificancePain-induced changes in the spatial distribution of muscle activity may induce overload of specific muscle regions in the long term.