Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and hyperalgesia in human surrogate models of neurogenic pain.

BACKGROUND: The effectiveness of Botulinum-neurotoxin A (BoNT/A) to treat pain in human pain models is very divergent. This study was conducted to clarify if the pain models or the route of BoNT/A application might be responsible for these divergent findings. METHODS: Sixteen healthy subjects (8 males, mean age 27 ± 5 years) were included in a first set of experiments consisting of three visits: (1) Visit: Quantitative sensory testing (QST) was performed before and after intradermal capsaicin injection (CAPS, 15 µg) on one thigh and electrical current stimulation (ES, 1 Hz) on the contralateral thigh. During stimulation pain and the neurogenic flare response (laser-Doppler imaging) were assessed. (2) Four weeks later, BoNT/A (Xeomin® , 25 MU) was injected intracutaneously on both sides. (3) Seven days later, the area of BoNT/A application was determined by the iodine-starch staining and the procedure of the (1) visit was exactly repeated. In consequence of these results, 8 healthy subjects (4 males, mean age 26 ± 3 years) were included into a second set of experiments. The experimental setting was exactly the same with the exception that stimulation frequency of ES was increased to 4 Hz and BoNT/A was injected subcutaneously into the thigh, which was stimulated by capsaicin. RESULTS: BoNT/A reduced the 1 Hz ES flare size (p < 0.001) and pain ratings (p < 0.01), but had no effect on 4 Hz ES and capsaicin-induced pain, hyperalgesia, or flare size, regardless of the depth of BoNT/A injection (i.c./s.c). Moreover, i.c. BoNT/A injection significantly increased warm detection and heat pain thresholds in naive skin (WDT, Δ 2.2 °C, p < 0.001; HPT Δ 1.8 °C, p < 0.005). CONCLUSION: BoNT/A has a moderate inhibitory effect on peptidergic and thermal C-fibers in healthy human skin. SIGNIFICANCE: The study demonstrates that BoNT/A (Incobotulinumtoxin A) has differential effects in human pain models: It reduces the neurogenic flare and had a moderate analgesic effects in low frequency but not high frequency current stimulation of cutaneous afferent fibers at C-fiber strength; BoNT/A had no effect in capsaicin-induced (CAPS) neurogenic flare or pain, or on hyperalgesia to mechanical or heat stimuli in both pain models. Intracutaneous BoNT/A increases warm and heat pain thresholds on naïve skin.

The effects of stress management on symptoms of upper respiratory tract infection, secretory immunoglobulin A, and mood in young adults.

OBJECTIVE: To investigate the efficacy of a stress management programme on symptoms of colds and influenza in 27 university students before and after the examination period. METHOD: The incidence of symptoms, levels of negative affect, and secretion rate of secretory immunoglobulin A (sIgA) were recorded for 5 weeks before treatment, for the 4 weeks of treatment, and for 8 weeks after treatment in treated subjects and in 25 others who did not participate in stress management. RESULTS: Symptoms decreased in treated subjects but not in controls during and after the examination period. Although sIgA secretion rate increased significantly after individual sessions of relaxation, resting secretion rate of sIgA did not increase over the course of the study. Negative affect decreased after examinations in both groups, but was not affected by treatment. CONCLUSION: Stress management reduced days of illness independently of negative affect and sIgA secretion rate. Although the component of treatment responsible for this effect has yet to be identified, psychological interventions may have a role in reducing symptoms of upper respiratory tract infection.

Psychological treatment for recurrent symptoms of colds and flu in children.

The effect of stress management and relaxation with guided imagery on upper respiratory tract infections (URTIs) was investigated in 45 children with a history of 10 or more infections in the past year. To investigate the influence of psychological treatment on mucosal immunity, secretory immunoglobulin A (sIgA) was measured before and during treatment. The number of symptomatic episodes during 13 weeks of monitoring was similar in treatment and waitlist conditions; however, episodes were shorter in stress management and guided imagery conditions than in the waitlist condition. Levels of sIgA increased toward the end of treatment. These findings were confirmed in a replication study. In addition, symptom reduction and improvements in psychological state persisted at 1-year follow-up. The findings suggest that psychological treatment interrupts a chronic illness cycle in children with symptoms of recurrent URTI.

The effect of Rapid Induction Analgesia on subjective pain ratings and pain tolerance.

The effect of Rapid Induction Analgesia (RIA) on pain tolerance and ratings of mechanically induced pain in the pain-sensitized forearm was investigated in 58 undergraduates. Posthypnotic suggestions of relaxation and analgesia did not influence pain ratings or tolerance, but relaxation ratings increased after RIA. When suggestions for analgesia were made throughout pain testing, ratings of pain unpleasantness at the pain tolerance point decreased more in the RIA group than in the attention control group. However, RIA did not influence pain threshold or tolerance. It was concluded that RIA was more effective in reducing subjective reports of pain (particularly the affective component) than in altering pain tolerance, and that maintenance of hypnotic suggestions was more effective than posthypnotic suggestions of comfort and relaxation in alleviating the affective component of pain.

The effect of moderate aerobic exercise and relaxation on secretory immunoglobulin A.

A deficiency in secretory immunoglobulin A (sIgA) is associated with recurrent upper respiratory tract infections both in the general community and in elite athletes. The aim of this paper was to investigate the effect of aerobic exercise and relaxation on various indices of sIgA in 12 male and 8 female adults who varied in levels of recreational activity. Salivary samples were obtained before, immediately after and 30 minutes after an incremental cycle ergometer test to fatigue, after 30 minutes of cycling at 30% or 60% of maximum heart rate, and after 30 minutes of relaxation with guided imagery. Each session was run on a separate day. When expressed in relation to changes in salivary flow rate, sIgA did not change after exercise. However, both the absolute concentration and secretion rate of sIgA increased during relaxation (167 +/- 179 microg x ml(-1), p < 0.001; and 37 +/- 71 microg x min(-1), p < 0.05 respectively). Nonspecific protein increased more than sIgA during incremental exercise to fatigue (decrease in the sIgA/protein ratio 92 +/- 181 microg x mg protein(-1), p < 0.05), but sIgA relative to protein did not change during relaxation. Our findings suggest that sIgA secretion rate is a more appropriate measure of sIgA than sIgA relative to protein, both for exercise and relaxation. These data suggest the possibility of using relaxation to counteract the negative effects of intense exercise on sIgA levels.

Rapid induction analgesia for the alleviation of procedural pain during burn care.

Burn patients must often endure intense pain during their regular dressing changes. The aim of the present study was to investigate the therapeutic effect of rapid induction analgesia (RIA) on resting and procedural pain, anticipatory anxiety, relaxation levels and medication consumption in 30 hospitalized burn patients. Patients rated levels of pain and relaxation for four burn care sessions. RIA was conducted twice on 15 patients, whereas dressing changes proceeded as usual in 15 control patients. When asked to recall pain during the dressing changes, patients remembered an experience which was worse in its entirety than the average of spot ratings taken during the burn care procedure. However, self-reported ratings of the sensory and affective components of pain decreased significantly during and after RIA, particularly in patients who became readily absorbed, and relaxation increased during burn care. Anticipatory anxiety decreased before dressing changes in the RIA group, and analgesic intake decreased between treatment sessions. The promising outcome of this study confirms RIA as a viable adjunct to narcotic treatment for pain control during burn care.

A cognitive behavioural approach to preventing anxiety during magnetic resonance imaging.

This study evaluated a relaxation intervention designed to prevent anxiety during magnetic resonance imaging (MRI), and assessed the development of fears in patients who felt anxious during the procedure. Patients were assigned to a control condition (no intervention; n = 52), relaxation before the scan (n = 44), or relaxation before and during the scan (n = 43). Compared to the control group, patients who practised relaxation showed reduced anxiety during the scan. Seven months or more after undergoing MRI, there was a positive correlation between anxiety experienced during the scan and the development of MRI-related fears. The intervention did not prevent the development of MRI-related fears at follow-up.

Secretory immunoglobulin A increases during relaxation in children with and without recurrent upper respiratory tract infections.

A diminished mucosal concentration of secretory immunoglobulin A (sIgA) in the upper respiratory tract may increase susceptibility to colds and flu. The aim of the present study was to determine whether sIgA increases during relaxation in children aged between 8 and 12 years with recurrent upper respiratory tract infections. Forty-five healthy children and 45 children with 10 or more upper respiratory tract infections in the previous year were randomly assigned to one of three experimental conditions: relaxation with suggestions to increase immune system proteins, relaxation alone, or a control condition. Samples of saliva were obtained before and after each condition. The concentration of sIgA in the saliva samples was later determined by measuring the rate of precipitation of antigen-antibody complexes to known concentration of sIgA antigen. The concentration of sIgA increased in the relaxation conditions but not in the control condition. The sIgA/albumin ratio (a more specific measure of local mucosal immunity than concentration) increased during the relaxation-suggestion condition but not during the relaxation or control conditions; however, both the concentration of sIgA and the sIgA/albumin ratio increased in proportion to subjective relaxation ratings. Neither response differed between healthy children and children with recurrent infections. The findings indicate that a disturbance in mucosal immunity in children with recurrent colds and flu does not limit increases in sIgA during relaxation. Higher preinfection levels of sIgA correlate with resistance to upper respiratory tract infection, so enhancing the sIgA concentration with relaxation techniques may help children with recurrent infection problems.