Pain patterns in chronic pancreatitis and chronic primary pain.

BACKGROUND: Abdominal pain is the most distressing symptom of chronic pancreatitis (CP), and current treatments show limited benefit. Pain phenotypes may be more useful than diagnostic categories when planning treatments, and the presence or absence of constant pain in CP may be a useful prognostic indicator. AIMS: This cross-sectional study examined dimensions of pain in CP, compared pain in CP with chronic primary pain (CPP), and assessed whether constant pain in CP is associated with poorer outcomes. METHODS: Patients with CP (N = 91) and CPP (N = 127) completed the Comprehensive Pancreatitis Assessment Tool. Differences in clinical characteristics and pain dimensions were assessed between a) CP and CPP and b) CP patients with constant versus intermittent pain. Latent class regression analysis was performed (N = 192) to group participants based on pain dimensions and clinical characteristics. RESULTS: Compared to CPP, CP patients had higher quality of life (p < 0.001), lower pain severity (p < 0.001), and were more likely to use strong opioids (p < 0.001). Within CP, constant pain was associated with a stronger response to pain triggers (p < 0.05), greater pain spread (p < 0.01), greater pain severity, more features of central sensitization, greater pain catastrophising, and lower quality of life compared to intermittent pain (all p values ≤ 0.001). Latent class regression analysis identified three groups, that mapped onto the following patient groups 1) combined CPP and CP-constant, 2) majority CPP, and 3) majority CP-intermittent. CONCLUSIONS: Within CP, constant pain may represent a pain phenotype that corresponds with poorer outcomes. CP patients with constant pain show similarities to some patients with CPP, potentially indicating shared mechanisms.

Short-term transcutaneous non-invasive vagus nerve stimulation may reduce disease activity and pro-inflammatory cytokines in rheumatoid arthritis: results of a pilot study.

Objective: Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease. Studies suggest that pro-inflammatory cytokines may be attenuated by the vagus nerve through the cholinergic anti-inflammatory pathway. We aimed to evaluate the anti-inflammatory effects of short-term transcutaneous non-invasive vagus nerve stimulation (n-VNS) applied to the cervical vagus nerve in patients with RA. Method: We conducted a single-centre, open-label, preliminary proof-of-concept study of n-VNS in two cohorts of participants with RA: one with high disease activity (n = 16) and one with low disease activity (n = 20). Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP), cardiac vagal tone, and pro-inflammatory cytokines were measured at baseline and after 1 and 4 days of n-VNS. Results: In the high disease activity group, n-VNS resulted in reductions in DAS28-CRP (4.1 to 3.8, p = 0.02), CRP (8.2 to 6 mg/mL, p = 0.01), and interferon-γ (29.8 to 22.5 pg/mL, p = 0.02). In the low disease activity group, there was no effect on DAS28-CRP, and n-VNS was associated with a decrease in cardiac vagal tone (p = 0.03) and a reduction in interleukin-10 (0.8 to 0.6 pg/mL, p = 0.02). Participants with high disease activity had lower baseline cardiac vagal tone than those with low disease activity (3.6 ± 2 vs 4.9 ± 3 linear vagal scale, p = 0.03). Cardiac vagal tone was negatively associated with DAS28-CRP (r = -0.37, p = 0.03). Overall, n-VNS was well tolerated. Conclusion: This study provides preliminary support for an anti-inflammatory effect of n-VNS in patients with RA. These findings warrant further investigation in larger placebo-controlled trials.

Vagal Nerve Stimulation-Modulation of the Anti-Inflammatory Response and Clinical Outcome in Psoriatic Arthritis or Ankylosing Spondylitis.

OBJECTIVES: The vagal nerve exerts an essential pathway in controlling the cholinergic anti-inflammatory reflex. Thus, the study is aimed at investigating the acute effect of a noninvasive transcutaneous vagus nerve stimulation on clinical disease activity and systemic levels of inflammation in patients with psoriatic arthritis or ankylosing spondylitis. METHODS: Twenty patients with psoriatic arthritis (PsA) and 20 patients with ankylosing spondylitis (AS) were included and stimulated bilaterally with a handheld vagal nerve stimulator for 120 seconds 3 times a day for 5 consecutive days. All patients were in remission. Cardiac vagal tone, clinical scores, CRP, and cytokine levels were assessed. RESULTS: In PsA and AS, decreased heart rate was observed, confirming compliance. Furthermore, in PsA, a clear reduction of clinical disease activity associated with a 20% reduction in CRP was shown. In AS, a reduction in interferon-γ, interleukin- (IL-) 8, and 10 was shown. No side effects were described. CONCLUSION: This open-label study provides support for an anti-inflammatory effect of transcutaneous vagus nerve stimulation in patients with psoriatic arthritis and ankylosing spondylitis. The modulated immune response and reduced disease activity and CRP-levels raise the fascinating possibility of using neuromodulation as an add-on to existing pharmacological treatments.

Cortical processing to anorectal stimuli after rectal resection with and without radiotherapy.

BACKGROUND: Bowel dysfunction is common after surgery for rectal cancer, especially when neoadjuvant radiotherapy is used. The role of sensory function in the pathogenesis remains obscure, and the aim of the present study was to characterize the sensory pathways of the brain-gut axis in rectal cancer patients treated with resection ± radiotherapy compared with healthy volunteers. METHODS: Sensory evaluation by (neo)rectal distensions was performed and sensory evoked potentials (SEPs) were recorded during rapid balloon distensions of the (neo)rectum and anal canal in resected patients with (n = 8) or without (n = 12) radiotherapy. Twenty healthy volunteers were included for comparison. (Neo)rectal latencies and amplitudes of SEPs were compared and spectral band analysis from (neo)rectal and anal distensions was used as a proxy of neuronal processing. RESULTS: Neorectal sensation thresholds were significantly increased in both patient categories (all p < 0.008). There were no differences in (neo)rectal SEP latencies and amplitudes between groups. However, spectral analysis of (neo)rectal SEPs showed significant differences between all groups in all bands (all p < 0.01). On the other hand, anal SEP analyses only showed significant differences between the delta (0-4 Hz), theta (4-8 Hz) and, gamma 32-50 Hz) bands (all p < 0.02) between the subgroup of patients that also received radiotherapy and healthy volunteers. CONCLUSIONS: Surgery for rectal cancer leads to abnormal cortical processing of neorectal sensation. Additional radiotherapy leads to a different pattern of central sensory processing of neorectal and anal sensations. This may play a role in the functional outcome of these patients.

Vagal influences in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease with a prevalence of 0.5-1% in Western populations. Conventionally, it is treated with therapeutic interventions that include corticosteroids, disease-modifying anti-rheumatic drugs, and biological agents. RA exerts a significant socio-economic burden and despite the use of existing treatments some patients end up with disabling symptoms. The autonomic nervous system (ANS) is a brain-body interface that serves to regulate homeostasis by integrating the external environment with the internal milieu. The main neural substrate of the parasympathetic branch of the ANS is the vagus nerve (VN). The discovery of the role of the ANS and the VN in mediating and dampening the inflammatory response has led to the proposal that modulation of neural circuits may serve as a valuable therapeutic tool. Recent studies have explored the role of the VN in this inflammatory reflex and have provided evidence that stimulation may represent a novel new therapeutic intervention. Accumulating evidence suggests that modulation of the parasympathetic tone results in a broad physiological multi-level response, including decreased pro-inflammatory cytokine response in terms of tumour necrosis factor-α, interleukin-1 (IL-1), and IL-6, and may result in an enhanced macrophage switch from M1 to M2 cells and potentially an increased level of the anti-inflammatory cytokine IL-10. Therefore, therapeutic electrical modulation of the VN may serve as an alternative, non-pharmacological, neuroimmunomodulatory intervention in RA in the future. This review gives a focused introduction to the mechanistic link between the ANS and the immune system.

Cardiac vagal tone, a non-invasive measure of parasympathetic tone, is a clinically relevant tool in Type 1 diabetes mellitus.

AIMS: To compare a novel index of parasympathetic tone, cardiac vagal tone, with established autonomic variables and to test the hypotheses that (1) cardiac vagal tone would be associated with established time and frequency domain measures of heart rate and (2) cardiac vagal tone would be lower in people with Type 1 diabetes than in a matched healthy cohort and lower still in people with established neuropathy. METHODS: Cardiac vagal tone is a validated cardiometrically derived index of parasympathetic tone. It is measured using a standard three-lead electrocardiogram which connects, via Bluetooth, to a smartphone application. A 5-min resting recording of cardiac vagal tone was undertaken and observational comparisons were made between 42 people with Type 1 diabetes and peripheral neuropathy and 23 without peripheral neuropathy and 65 healthy people. In those with neuropathy, 24-h heart rate variability values were compared with cardiac vagal tone. Correlations between cardiac vagal tone and clinical variables were also made. RESULTS: Cardiac vagal tone was lower in people with established neuropathy and Type 1 diabetes in comparison with healthy participants [median (interquartile range) linear vagal scale 3.4 (1.6-5.5 vs 7.0 (5.5-9.6); P < 0.0001]. Cardiac vagal tone was positively associated with time (r = 0.8, P < 0.0001) and frequency domain markers of heart rate variability (r = 0.75, P < 0.0001), representing established measures of parasympathetic function. Cardiac vagal tone was negatively associated with age (r=-0.32, P = 0.003), disease duration (r=-0.43, P < 0.0001) and cardiovascular risk score (r=-0.32, P = 0.006). CONCLUSIONS: Cardiac vagal tone represents a convenient, clinically relevant method of assessing parasympathetic nervous system tone, potentially facilitating the earlier identification of people with Type 1 diabetes who should undergo formal autonomic function testing.

A comprehensive pain assessment tool (COMPAT) for chronic pancreatitis: Development, face validation and pilot evaluation.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) pain is challenging to treat. Treatment selection is hampered by there being no validated pain assessment tool that accounts for the complexity of CP pain and its underlying mechanisms. This study aims to develop a comprehensive pain assessment tool (COMPAT) specific for CP, evaluate its face validity with experts and patients and test it with a pilot cohort of patients. METHODS: COMPAT was developed from existing pain assessment tools and a literature review. Face validity was conducted by pancreatologists and CP patients using an item-content validity index for importance, relevance and clarity. Subsequent revisions were made to COMPAT. A pilot cohort of CP patients tested COMPAT. RESULTS: COMPAT was developed and covered all important aspects of CP pain. Experts and CP patients reported that 70% of questions were important and relevant to CP pain. Most experts were willing to use COMPAT in clinic, ward/hospital and research settings. The most common location of pain was the epigastrium and food was the most important trigger. Pain Pattern C (constant background pain with pain attacks), had significantly higher frequency of pain attacks, higher opioid use, and affective descriptors of pain than Pattern A (pain attacks with no background pain). CONCLUSIONS: COMPAT has high face validity and met with high acceptance. CP patients successfully self-reported their pain with COMPAT. The results reveal many differences in the CP pain within the pilot cohort, which may reflect different mechanisms of pain. A larger prospective cohort study is planned to further validate COMPAT.

An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers.

Background: There is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg. Methods: Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design. The main end-point of the study was the effect of treatment on the ventilatory response to hypercapnia and ventilation at an extrapolated end-tidal PCO2 of 7.3 kPa (55 mmHg, VE55); VE55 was assessed prior and for 6-h following drug intake. Results: All three treatments had typical opioid effects on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference -5.0 L min-1, 95% confidence interval: -7.1 to -2.9 L min-1, P<0.01), but not larger than tapentadol 150 mg (oxycodone vs. tapentadol 150 mg: P>0.05). Conclusions: In this exploratory study we observed that both tapentadol and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg had a modest respiratory advantage over oxycodone 20 mg. Further studies are needed to explore how these results translate to the clinical setting.

Assessment of colorectal length using the electromagnetic capsule tracking system: a comparative validation study in healthy subjects.

AIM: We aimed to determine colorectal length with the 3D-Transit system by describing a 'centreline' of capsule movement and comparing it with known anatomy, as determined by magnetic resonance imaging (MRI). Further, we aimed to test the day-to-day variation of colorectal length assessed with the system. METHOD: The 3D-Transit system consists of electromagnetic capsules that can be tracked as they traverse the gastrointestinal tract. Twenty-five healthy subjects were examined with both 3D-Transit and MRI. Another 21 healthy subjects were examined with 3D-Transit on two consecutive days. RESULTS: Computation of colorectal length from capsule passage was possible for 60 of the 67 3D-Transit recordings. The length of the colorectum measured with MRI and 3D-Transit was 95 (75-153) cm and 99 (77-147) cm, respectively (P = 0.15). The coefficient of variation (CV) between MRI and 3D-Transit was 7.8%. Apart from the caecum/ascending colon being 26% (P = 0.002) shorter on MRI, there were no other differences in total or segmental colorectal lengths between methods (all P > 0.05). The length of the colorectum measured with 3D-Transit on two consecutive days was 102 (73-119) cm and 103 (75-123) cm (P = 0.67). The CV between days was 7.3%. CONCLUSION: The 3D-Transit system allows accurate and reliable determination of colorectal length compared with MRI-derived colorectal length and between days. Antegrade or retrograde capsule movement relative to this centreline, as well as the length and speed of movements, may be determined by future studies to allow better classification and treatment in patients with dysmotility.

Venlafaxine and oxycodone effects on human spinal and supraspinal pain processing: a randomized cross-over trial.

Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids, the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine affect spinal and supraspinal pain processing. Twenty volunteers were included in this randomized cross-over study comparing 5-day treatment with venlafaxine, oxycodone and placebo. As a proxy of the spinal pain transmission, the nociceptive withdrawal reflex (NWR) to electrical stimulation on the sole of the foot was recorded at the tibialis anterior muscle before and after 5 days of treatment. For the supraspinal activity, 61-channel electroencephalogram evoked potentials (EPs) to the electrical stimulations were simultaneously recorded. Areas under curve (AUCs) of the EMG signals were analyzed. Latencies and AUCs were computed for the major EP peaks and brain source analysis was done. The NWR was decreased in venlafaxine arm (P = 0.02), but the EP parameters did not change. Oxycodone increased the AUC of the EP response (P = 0.04). Oxycodone also shifted the cingulate activity anteriorly in the mid-cingulate-operculum network (P < 0.01), and the cingulate activity was increased while the operculum activity was decreased (P = 0.02). Venlafaxine exerts its effects on the modulation of spinal nociceptive transmission, which may reflect changes in balance between descending inhibition and descending facilitation. Oxycodone, on the other hand, exerts its effects at the cortical level. This study sheds light on how opioids and SNRI drugs modify the human central nervous system and where their effects dominate.

Does Sacral Nerve Stimulation Improve Continence Through Enhanced Sensitivity of the Anal Canal? A Pilot Study.

BACKGROUND: It has been suggested that the effects of sacral nerve stimulation against fecal incontinence involve neuromodulation at spinal or supraspinal levels. OBJECTIVE: This study aims to investigate the afferent sensory pathways from the anorectum before and during sacral nerve stimulation. DESIGN: This is an explorative study. PATIENTS: Fifteen women with idiopathic fecal incontinence (mean age, 58 ± 12.2 years) were selected. INTERVENTIONS: Cortical evoked potentials were recorded during repeated rapid balloon distension of the rectum and the anal canal both before and during temporary sacral nerve stimulation. Stimuli applied were individualized according to the subjective urge to defecate. MAIN OUTCOME MEASURES: The main outcomes measured were 1) stimulus intensity, 2) latencies and amplitudes of cortical evoked potentials, and 3) spectral content in predefined frequency bands of cortical evoked potentials. RESULTS: The median Wexner fecal incontinence score improved from 15.5 ± 3.6 before to 6.7 ± 5 during sacral nerve stimulation (p < 0.001). Sacral nerve stimulation did not affect the threshold for urge to defecate during rectal distension (p = 0.64) but reduced the threshold from stimulation of the anal canal by 50% (p = 0.03). No statistically significant differences were found in latencies, amplitudes, or spectral analysis. LIMITATIONS: This is a pilot study of limited size. CONCLUSIONS: In patients with idiopathic fecal incontinence, sacral nerve stimulation reduced the threshold for urge to defecate elicited from the anal canal, whereas supraspinal responses remained unaltered. This may suggest that sacral nerve stimulation, at least in part, acts via somatic afferent fibers enhancing anal sensation.

Short-term oxycodone treatment does not affect electrogenic ion transport in isolated mucosa from the human rectosigmoid colon.

OBJECTIVE: Opioid therapy is associated with altered secretion and motility of the gut. The relative contribution of decreased secretion to the development of opioid-induced constipation remains unknown. MATERIALS AND METHODS: Twenty-five healthy males were treated with oxycodone for 5 d in a placebo-controlled, randomised cross-over design. Gastrointestinal adverse effects were assessed with validated questionnaires (bowel function index and gastrointestinal symptom rating scale). Rectosigmoid mucosal biopsies were taken at baseline and on day 5 during both treatments and mounted in Ussing chambers. Electrogenic ion transport parameters (short circuit current (SCC) and slope conductance) were measured after addition of secretagogues (prostaglandin E2 (PGE2) (6 µm), theophylline (400 µm)), and an inhibitor (ouabain (200 µm)). Additionally, morphine (50 µm) was added to investigate the direct opioid effect on colonic mucosa. RESULTS: Questionnaires showed pronounced bowel symptoms, including constipation during oxycodone treatment (eight-fold increase in bowel function index score from day 1 to day 5 (p < 0.001) while no significant change occurred during placebo treatment (p = 0.47). Basal SCC and slope conductance did not differ between treatments (all p > 0.05) and application with PGE2, theophylline, and ouabain yielded comparable results on all examinations (all p > 0.05). Morphine application consistently did not evoke a change in ion transport. CONCLUSION: Compared to placebo, epithelial electrogenic ion transport is not altered in mucosal biopsies from the rectosigmoid colon following 5-d oxycodone treatment. The secretory mechanisms in isolated mucosa appear to play a negligible role in the development of opioid-induced constipation.

Esophagogastric junction distensibility in hiatus hernia.

Hiatus hernia is known to be an important risk factor for developing gastroesophageal reflux disease. We aimed to use the endoscopic functional lumen imaging probe (EndoFLIP) to evaluate the functional properties of the esophagogastric junction. EndoFLIP assessments were made in 30 patients with hiatus hernia and Barrett's esophagus, and in 14 healthy controls. The EndoFLIP was placed straddling the esophagogastric junction and the bag distended stepwise to 50 mL. Cross-sectional areas of the bag and intra-bag pressures were recorded continuously. Measurements were made in the separate sphincter components and hiatus hernia cavity. EndoFLIP measured functional aspects such as sphincter distensibility and pressure of all esophagogastric junction components and visualized all hiatus hernia present at endoscopy. The lower esophageal sphincter in hiatus hernia patients had a lower pressure (e.g. 47.7 ± 13.0 vs. 61.4 ± 19.2 mm Hg at 50-mL distension volume) and was more distensible (all P < 0.001) than the common esophagogastric junction in controls. In hiatus hernia patients, the crural diaphragm had a lower pressure (e.g. 29.6 ± 10.1 vs. 47.7 ± 13.0 mm Hg at 50-mL distension volume) and was more distensible (all P < 0.001) than the lower esophageal sphincter. There was a significant association between symptom scores in patients and EndoFLIP assessment. Conclusively, EndoFLIP was a useful tool. To evaluate the presence of a hiatus hernia and to measure the functional properties of the esophagogastric junction. Furthermore, EndoFLIP distinguished the separate esophagogastric junction components in hiatus hernia patients, and may help us understand the biomechanics of the esophagogastric junction and the mechanisms behind hiatal herniation.

Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy.

BACKGROUND: Tapentadol is an analgesic agent for treatment of acute and chronic pain that activates the µ-opioid receptor combined with inhibition of neuronal norepinephrine reuptake. Both mechanisms are implicated in activation of descending inhibitory pain pathways. In this study, we investigated the influence of tapentadol on conditioned pain modulation (CPM, an experimental measure of endogenous pain inhibition that gates incoming pain signals as a consequence of a preceding tonic painful stimulus) and offset analgesia (OA, a test in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation). METHODS: Twenty-four patients with diabetic polyneuropathy (DPN) were randomized to receive daily treatment with tapentadol sustained-release (SR) [average daily dose 433 (31) mg] or placebo for 4 weeks. CPM and OA were measured before and on the last day of treatment. RESULTS: Before treatment, none of the patients had significant CPM or OA responses. At week 4 of treatment, CPM was significantly activated by tapentadol SR and coincided with significant analgesic responses. CPM increased from 9.1 (5.4)% (baseline) to 14.3 (7.2)% (placebo) and 24.2 (7.7)% (tapentadol SR, P<0.001 vs placebo); relief of DPN pain was also greater in patients treated with tapentadol than placebo (P=0.028). Neither placebo nor tapentadol SR treatment had an effect on the magnitude of the OA responses (P=0.78). CONCLUSIONS: Tapentadol's analgesic effect in chronic pain patients with DPN is dependent on activation of descending inhibitory pain pathways as observed by CPM responses. CLINICAL TRIAL REGISTRATION: The study was registered at trialregister.nl under number NTR2716.

Patients with esophageal motility disorders show distinct patterns based on axial force measurements.

BACKGROUND: Using manometry, the classification of motility-related disorders in the esophagus is vague and overlapping. We present a new method, which combines manometry and axial force measurements in a single catheter. AIM: The aim was to examine the manometric and axial force recordings during swallows. METHODS: Recordings from 20 patients suffering from diffuse esophageal spasms (DES) (8), achalasia (5) and other diseases including gastro-oesophageal reflux (7) were compared to recordings made in ten healthy subjects. The probe was capable of measuring axial force 6.5-cm proximal to the lower esophageal sphincter (LES) and pressures 8-, 10- and 12-cm proximal to the LES. After insertion, five dry and five wet swallows were made. Swallows were repeated with 0, 2, 4 and 6 ml of water in a bag mounted distal to the axial force recording site. Each contraction was analysed for duration and amplitude, and was categorised according to its configuration. RESULTS: The number of failed contractions measured with axial force was lower for the achalasia (P < 0.001) and DES groups (P < 0.001) compared to the healthy volunteers. The number of multi-peaked contractions was unchanged for the achalasia and DES groups while it increased for the group of healthy volunteers. On several occasions a negative traction force was encountered though the manometric pattern appeared normal. CONCLUSIONS: Measurements of axial force generated by primary peristalsis provide additional information about esophageal neuromuscular function in different diseases that is not demonstrable with manometry alone.

Botulinum toxin type A reduces histamine-induced itch and vasomotor responses in human skin.

BACKGROUND: Clinical evidence has revealed the antipruritic effect of botulinum toxin type A (BoNT/A). BoNT/A is believed to be effective against itch as it inhibits the release of acetylcholine as well as some other substances that may be involved in itch. OBJECTIVES: To investigate the effect of subcutaneous administration of BoNT/A on experimentally histamine-induced itch in human skin. METHODS: In this double-blind, placebo-controlled study, 14 healthy men (mean +/- SD age 26.3 +/- 2.6 years) received BoNT/A (Botox; Allergan, Irvine, CA, U.S.A.; 5 U) and isotonic saline on the volar surface of either forearm. Histamine prick tests were performed four times at the treatment sites (before treatment, and days 1, 3 and 7 after treatment). The itch intensity (as rated on a 0-10 visual analogue scale), itch area, neurogenic inflammation (visible flare area), blood flow (laser Doppler) and cutaneous temperature (thermographic images) were measured over the course of the trials. RESULTS: BoNT/A reduced the histamine-induced itch intensity (F(1,39) = 30.2, P < 0.001) and itch area (F(1,39) = 8.8, P = 0.011) compared with saline at all time points after treatment. The duration of itch was also shorter for BoNT/A-treated areas (F(1,39) = 19.4, P < 0.001), with a peak effect at day 7. The flare area was smaller in the BoNT/A-treated arm compared with the saline-treated arm at all time points after treatment (F(1,39) = 15.4, P = 0.002). Findings from blood flow (F(1,26) = 177.3, P < 0.001) and temperature measurements (F(1,26) = 27.6, P < 0.001) clearly showed the suppressive effect of BoNT/A on vasomotor reactions, with the maximal effect on days 3 and 7. CONCLUSIONS: BoNT/A reduced the itch intensity, blood flow and neurogenic inflammation in response to the histamine prick test in human skin. The findings could be applicable in the treatment of some pruritic conditions that can be difficult to treat with conventional treatments.

Gastrointestinal sensations and pain: a review on basic, experimental and clinical findings.

Painful sensations from the gastrointestinal (GI) tract are common symptoms in the clinic but the etiology is often not fully understood and underlying diseases can be difficult to diagnose and treat successfully. In clinical practice, GI pain is often diffuse and pain referral to somatic structures can be the presenting symptom. In addition, concomitant symptoms from the autonomic and enteric nervous system can be present and affect the pain experience. To examine patients suffering from GI pain, basic knowledge about the GI pain system is essential and assists to explain the often complex and diverse symptoms. Information about anatomical and physiological characteristics of the GI pain system come from basic, experimental and clinical research, which have also gained insight into pain mechanisms underlying chronic GI pain. Evidence for sensitisation at the peripheral and central level of the nervous system seems to be of importance. These findings have major implication for the evaluation and treatment of patients suffering from GI pain.

Pain in chronic pancreatitis: the role of neuropathic pain mechanisms.

Pain mechanisms in patients with chronic pancreatitis are incompletely understood and probably multifactorial. Recently, evidence from experimental human pain research has indicated that in many of these patients pain processing in the central nervous system is abnormal and mimics that seen in neuropathic pain disorders. The current review focuses on several lines of evidence supporting this hypothesis. Hence, the spontaneous and postprandial pain in chronic pancreatitis may reflect the characteristic pain features seen in patients with neuropathic pain. Biochemical and histopathological findings in tissues from patients with chronic pancreatitis are similar to those observed in patients with other nerve fibre lesions. Experimental studies have shown that patients with chronic pancreatitis show signs of spinal hyper-excitability counter-balanced by segmental and descending inhibition. Changes in the brain with cortical reorganisation to gut stimulation and increased activity in specific electroencephalographic features characteristic for neuropathic pain are also seen in patients with chronic pancreatitis. Finally, principles involved in the treatment of pancreatic pain have many similarities with those recommended in neuropathic pain disorders. In conclusion, a mechanism-based understanding of pain in chronic pancreatitis may have important implications for the treatment.

Measurement of the axial force during primary peristalsis in the oesophagus using a novel electrical impedance technology.

The oesophagus serves to transport food and fluid from the pharynx to the stomach. Oesophageal function is usually evaluated by means of manometry which is a proxy of the force in the radial direction. However, force measurements in the axial direction will provide a better measure of oesophageal transport function. The aim of this study was to develop a probe based on electrical impedance measurements to quantify the axial force generated by oesophageal contractions, i.e. probe elongation was associated with the axial force. Calibration with weights up to 200 g was done. The dispersion, creep, temperature and bending dependence were studied at the bench. Subsequently, the probe was tested in vivo in a healthy human volunteer. The probe showed good reproducibility and the dispersion was <0.04. Some dependence on temperature, creep and bending was found. Interpolation of the calibration curves made it possible to compensate for temperature fluctuations. The maximum deviation was 6.1 +/- 3.7% at loads of 50 g. The influence of creep showed a maximum net creep of 6.1 g after 8 s. The swallowed bolus size correlated with the axial force measurements (P = 0.038) but not with manometric measurements. In conclusion, the new technique measures axial force in the oesophagus and may in the future provide valuable information about oesophageal function.