Effectiveness and Tolerability of a Moderate Dose of Tapentadol Prolonged Release for Managing Severe, Chronic Low Back Pain with a Neuropathic Component: An Open-label Continuation Arm of a Randomized Phase 3b Study.

OBJECTIVE: To evaluate the effectiveness and tolerability of tapentadol prolonged release (PR) for severe, chronic low back pain with a neuropathic component in a subpopulation that achieved adequate pain relief with tapentadol PR 300 mg/day in a randomized, double-blind, phase 3b study. METHODS: Patients with painDETECT "unclear" or "positive" ratings and pain intensity ≥ 6 (11-point NRS-3 [average 3-day pain intensity]) were titrated to tapentadol PR 300 mg/day over 3 weeks. A subpopulation with pain intensity < 4 continued receiving tapentadol PR 300 mg/day during an 8-week, open-label continuation arm. For the primary study population, patients with ≥ 1-point decrease from baseline and pain intensity ≥ 4 were randomized to tapentadol PR 500 mg/day or tapentadol PR 300 mg/day plus pregabalin 300 mg/day during a concurrent 8-week, double-blind comparative period. RESULTS: From baseline to end of titration and to final evaluation, significant improvements were observed in pain intensity (mean [SD] changes from baseline to: end of titration; - 5.3 [1.78]; final evaluation; - 5.2 [2.39]; both P < 0.0001), neuropathic pain symptoms, and quality-of-life measures in the open-label continuation arm, with greater improvements in this selected subpopulation than in either group in the primary study population. A favorable tolerability profile was observed, with incidences of all individual treatment-emergent adverse events ≤ 5.1% during the continuation period. CONCLUSIONS: A subpopulation of patients with low back pain with a neuropathic component responded very well to tapentadol PR 300 mg/day, with significant improvements in pain intensity, neuropathic pain-related symptoms, and quality of life. Further research is needed to identify factors associated with a very positive treatment response.

Phantom limb pain in daily practice--still a lot of work to do!

OBJECTIVES: Effective treatment of phantom limb pain (PLP, pain felt in the part of the body of an amputated limb) is still difficult to achieve, and improved treatment is needed. It is therefore of paramount interest to understand the current practice of PLP therapy outside pain centers. DESIGN: As a part of a nationwide survey, 537 amputees were asked 11 questions related to their treatment experiences and the pain relief. Furthermore, the patients' opinion about the quality of medical care was also asked. RESULTS: Five hundred thirty-seven out of 1088 amputees returned the questionnaire (49.4%). Four hundred (74.5%) suffered from PLP. The patients rated their caregivers' knowledge about PLP lower than their own. Many (41.6%) of PLP patients had never been informed about the possibility of occurrence and mechanisms of PLP. The vast majority of the PLP patients did not try any treatment. Among those treated, more than 30% consulted more than three physicians for beneficial treatment. A >50% pain reduction was achieved in only 12.7% of PLP patients. The most successful treatments were opioids (67.4%) and anticonvulsants (51.7%). Surgery was performed in 46.4% of all PLP patients and in 29.7% due to a clinically suspected neuroma. After surgery, pain was worse or unchanged in 50% and improved in 41.6%, and 7.4% were pain-free. CONCLUSIONS: Our results suggest that there are primary needs for better information about PLP pathophysiology and treatment not only for patients but also for caregivers. Limited therapeutic success reveals a further need for increased research in PLP management.

The effect of deep and slow breathing on pain perception, autonomic activity, and mood processing--an experimental study.

OBJECTIVE: Deep and slow breathing (DSB) techniques, as a component of various relaxation techniques, have been reported as complementary approaches in the treatment of chronic pain syndromes, but the relevance of relaxation for alleviating pain during a breathing intervention was not evaluated so far. METHODS: In order to disentangle the effects of relaxation and respiration, we investigated two different DSB techniques at the same respiration rates and depths on pain perception, autonomic activity, and mood in 16 healthy subjects. In the attentive DSB intervention, subjects were asked to breathe guided by a respiratory feedback task requiring a high degree of concentration and constant attention. In the relaxing DSB intervention, the subjects relaxed during the breathing training. The skin conductance levels, indicating sympathetic tone, were measured during the breathing maneuvers. Thermal detection and pain thresholds for cold and hot stimuli and profile of mood states were examined before and after the breathing sessions. RESULTS: The mean detection and pain thresholds showed a significant increase resulting from the relaxing DSB, whereas no significant changes of these thresholds were found associated with the attentive DSB. The mean skin conductance levels indicating sympathetic activity decreased significantly during the relaxing DSB intervention but not during the attentive DSB. Both breathing interventions showed similar reductions in negative feelings (tension, anger, and depression). CONCLUSION: Our results suggest that the way of breathing decisively influences autonomic and pain processing, thereby identifying DSB in concert with relaxation as the essential feature in the modulation of sympathetic arousal and pain perception.

Botulinum toxin type B in the treatment of residual limb hyperhidrosis for lower limb amputees: a pilot study.

OBJECTIVE: Botulinum toxin type A is established in the treatment of hyperhidrosis. This pilot study was designed to prove the alleviating effect of botulinum toxin type B (BTX-B) in sweating of the residual limb, as BTX-B, even in low doses, is supposed to possess a more specific action in sympathetic nerves than botulinum toxin type A does at a wider radius of diffusion. DESIGN: Nine lower limb amputees received 1750 U BTX-B injected at the site of maximum sweating. Before injections and 4 wks and 3 mos after, patients rated their impairments regarding sweating of the residual limb, steadiness of gait, use of the prosthetic device, quality-of-life, work performance, quality of sleep, and skin problems using a numeric rating scale (NRS; 0-10). RESULTS: Sweating of the residual limb before BTX-B application was rated a median of 7 (interquartile range, 6-10) on the NRS, with significant improvements after 4 wks (NRS, 3 [2-4]; P = 0.027) and 3 mos (NRS, 3 [1-4]; P = 0.020). Impaired quality of artificial limb use likewise improved from a baseline NRS of 9 (5-9) to 2 (1-4) after 4 wks and 3 (1-4) (P = 0.027) after 3 mos, consistent with limited duration of use (P = 0.023). Steadiness of gait, quality-of-life, and work performance increased accordingly, and skin problems decreased clearly but not significantly. Unexpectedly, stump pain was also reduced (baseline: NRS, 5 [4-8]; 4 wks: NRS, 4 [3-5], P = 0.109; 3 mos: NRS, 3 [2-4], P = 0.008). CONCLUSIONS: Low-dose BTX-B significantly reduced sweating of the residual limb, thereby improving the use of the artificial limb, steadiness of gait, and quality-of-life. Because this has a tremendous impact on amputees, we are in dire need for systematic, larger studies.

Management of phantom pain with a textile, electromagnetically-acting stump liner: a randomized, double-blind, crossover study.

The treatment of phantom pain is frequently dissatisfying. We wanted to find out whether an electromagnetically shielding stump stocking interwoven with metal (medipro(R)Liner RELAX [medi Bayreuth, Bayreuth, Germany]) could have a positive effect on phantom pain. A double-blind, randomized, crossover trial in a total of 30 leg amputees compared the experimental (=verum) silicon liner (VL) fitted to the amputation stump with a dummy (=placebo) liner (PL). Each liner was worn for two weeks after a two-week baseline period. Daily documentation focused on phantom pain, quality of sleep and improvement of well-being. Twenty-seven of 30 patients completed the 6-week study, and 22 documentations proved valid. On a 0-10 numeric rating scale (NRS), the median pain intensity before treatment was 4, and the median of maximum pain was 6. VL versus PL reduced pain significantly more often (P=0.008), the odds ratio being 5.95. The degree of pain reduction was likewise highly significant (<0.001). Wilcoxon's matched-pairs signed-rank test for the medians of daily maximum pain showed a significant reduction for both PL (P < 0.001) and VL (P <0.001) as compared to baseline, with VL being highly superior again (P < 0.001) versus PL. The experimental device also led to significant amelioration of general well-being (P = 0.037) with an odds ratio of 3.85, and an improvement in the quality of sleep, which was not significantly different than PL (P = 0.223). In this study, the influence of a silicon liner with electromagnetically protecting properties on phantom pain was highly significant. The mechanisms underlying this effect are unclear. Possibilities include reduction of ectopic neuroma activity, shielding from possible electromagnetic weather impulses (sferics), or analgesic effects of changes in the electromagnetic field. PET or fMRI examination with or without a shielding silicon liner might help to elucidate this observation further.

Effects of botulinum toxin type B on stump pain and involuntary movements of the stump.

Patients who had previously undergone amputation of the arm (n = 2) or leg (n = 2) were treated with botulinum toxin type B injections at several trigger points of their stump musculature. We administered a total dose of 2500 IU of botulinum toxin type B (Neurobloc, Elan Pharma, Munich, Germany) to the arm amputation stumps, 5000 IU for one amputation of the lower leg, and 2500 IU to the other lower leg amputation of a patient with a very low baseline body weight. Two patients reported that the injection was very painful. All patients experienced a reduction in stump pain, which lasted for many weeks. Other reports included a reduction in the frequency of pain attacks, cessation of "balloon feelings," improvement in stump allodynia, and decreased occurrence of involuntary stump movements. In addition, quality of sleep at night significantly improved in one patient. Botulinum toxin type B can therefore be regarded as a new treatment option for possible improvements in the rehabilitation of amputees.

Does botulinum toxin A make prosthesis use easier for amputees?

Four post-amputation patients (1 with phantom pain, 3 with stump pain) were each treated with 100 IU botulinum toxin A, divided between several trigger points in the distal stump musculature. In 1 female patient (along with a pronounced reduction in phantom pain) hyperhidrosis of the stump ceased completely, probably after diffusion of the drug into the dermal sweat glands, leading to longer and safer use of the prosthesis. Intentional intradermal injection for this issue therefore could be valuable. Another patient was able to use her prosthesis for the whole day again after botulinum toxin A treatment for substantial stump pain, compared with only 4 hours a day before treatment. In 2 male patients, stump pain while wearing the prosthesis subsided to a considerable extent, 1 of the 2 reported an improvement in steadiness of gait. We suggest that stump treatment with botulinum toxin in rehabilitative medicine should be investigated in more detail.