[Postherpetic neuralgia of the left trigeminus nerve V1 : Successful therapy with capsaicin 8% patch]. / Post-Zoster-Neuralgie des linken Trigeminusastes V1 : Erfolgreiche Therapie mit Capsaicin 8 %­Pflaster.

A 68-year-old patient suffered from postzoster neuralgia with severe pain of the left trigeminal nerve V1. Despite medication with gabapentin 1800 mg/d, oxacarbazepine 600 mg, tapentadol 500 mg/d, amitriptyline 20 mg as well as ambroxol 20% ointment and lidocaine patch topically, the pain reached an intensity of 8-10 on the numeric rating scale (NRS). Wearing a CPAP (continuous positive airway pressure) mask at night to treat a sleep apnea was impossible or the mask was leaking under lidocaine patch, only topical ambroxol 20% brought a certain pain relief. Lack of sleep, a strongly reduced quality of life and massive exhaustion followed quickly. Due to a fall the systemic medication could not be increased. Also lidocaine infusions with dexamethasone and supraorbitalis blockades were unsuccessful, and a ganglionic local opioid analgesia (GLOA) was anatomically not feasible. Therefore, 8 weeks after the onset of the disease, treatment with capsaicin 8% for 60 min on the face was performed. After only one week, 20-30% pain relief was achieved, sometimes even freedom from pain. Six weeks after application, the average pain during the day was only NRS 3/10 despite a considerable reduction in oral medication. Three months after the second treatment, the patient was almost pain-free during the day. Topical capsaicin 8% patch is, in our opinion, also safe and successful to use on the face with appropriate experience of the user.

Treatment of painful radiculopathies with capsaicin 8% cutaneous patch.

BACKGROUND AND OBJECTIVE: The treatment of neuropathic pain due to low-back (lumbosacral) radiculopathies, a common source of neuropathic pain, is challenging and often requires a multimodal therapeutic approach. The capsaicin 8% patch is the first topical analgesic licensed for peripheral neuropathic pain. To evaluate this treatment, a subset of patients with painful radiculopathy (lumbar and cervical, including ventral and dorsal rami) enrolled into the multicenter, non-interventional QUEPP study (Qutenza 2 - safety and effectiveness in peripheral neuropathic pain) was analyzed. METHODS: Of the 1044 study participants, 50 were diagnosed with painful radiculopathy as only peripheral neuropathic pain syndrome and were eligible for evaluation. Patients received a single treatment (visit 1) with follow-up visits 2-5 at weeks 1-2, 4, 8 and 12. Parameters assessed at all visits included pain intensity, neuropathy symptoms and side effects. Quality of life (SF-12) and painDETECT 1 questionnaires were completed at baseline and final visit. Data was analyzed by patch application site and duration of pain. RESULTS: Topical treatment led to a significant decrease of pain intensity between weeks 1/2 and week 12 versus baseline at the application sites representing dermatomes of ventral (N = 26) and dorsal rami (N = 13) of spinal nerves. A significant decline (p ≤ .001) of numeric pain rating scale scores was observed between weeks 1/2 following patch application and the end of observation (week 12) in the overall radiculopathy group (N = 50), and the groups with either 3 months to 2 years (N = 14) or >2 years (N = 23) duration of pain. Pain relief of at least 30% was observed in 50.0%, 71.4% and 39.1% of patients in the respective groups. Four patients experienced in total seven adverse drug reactions (application site pain or pruritus). CONCLUSION: Effective neuropathic pain relief was observed after patch application within the innervation territories of both dorsal and ventral branches of the spinal nerve. Further controlled randomized trials are indicated.

Topical ambroxol for the treatment of neuropathic pain. An initial clinical observation.

BACKGROUND: Neuropathic pain is difficult to treat, and the available options are often inadequate. The expectorant ambroxol also acts as a strong local anaesthetic and blocks sodium channels about 40 times more potently than lidocaine. It preferentially inhibits the channel subtype Nav 1.8, which is expressed especially in nociceptive C-fibres. In view of the low toxicity of ambroxol, it seemed reasonable to try using it for the treatment of neuropathic pain that failed to respond to other standard options. MATERIAL AND METHODS: The medical records of seven patients with severe neuropathic pain and pain reduction following topical ambroxol treatment are reported retrospectively. As standard therapies had not proved sufficient, a topical ambroxol 20% cream was repeatedly applied by the patients in the area of neuropathic pain. RESULTS: The reasons for neuropathic pain were postherpetic neuralgia (2 ×), mononeuropathy multiplex, phantom pain, deafferentation pain, postoperative neuralgia and foot neuropathy of unknown origin. The individual mean pain intensity reported was between 4 and 6/10 (NRS), maximum pain at 6-10/10 (NRS). The pain reduction achieved individually following ambroxol cream was 2-8 points (NRS) within 5-30 min and lasted for 3-8 h. Pain attacks were reduced in all five patients presenting with this problem. Four patients with no improvement after lidocaine 5% and one patient with no response to capsaicin 8% nevertheless experienced a pain reduction with topical ambroxol. No patient reported any side effects or skin changes during a treatment that has since been continued for up to 4 years. CONCLUSION: Ambroxol acts as a strong local anaesthetic and preferentially inhibits the nociceptively relevant sodium channel subtype Nav 1.8. For the first time, we report below on a relevant pain relief following topical ambroxol 20% cream in patients with neuropathic pain. In view of the positive side effect profile, the clinical benefit in patients with pain should be investigated further.

[Topical ambroxol for the treatment of neuropathic pain: A first clinical observation. German version]. / Topisches Ambroxol zur Behandlung neuropathischer Schmerzen: Eine erste klinische Beobachtung.

BACKGROUND: Neuropathic pain is difficult to treat and available options are frequently not sufficient. The expectorant ambroxol also works as a strong local anesthetic and blocks sodium channels about 40 times more potently than lidocaine. Ambroxol preferentially inhibits the channel subtype Nav 1.8, which is expressed particularly in nociceptive C fibers. Due to the low toxicity, topical ambroxol seemed to represent a reasonable therapeutic attempt for treatment of neuropathic pain resistant to other standard options. MATERIALS AND METHODS: Medical records of 7 patients with severe neuropathic pain, in whom many attempts at treatment with approved substances were not sufficient or possible, are reported retrospectively. Patients were then treated with topical ambroxol 20% cream applied in the area of neuropathic pain. RESULTS: Causes of neuropathic pain were postherpetic neuralgia (2-×), mononeuropathy multiplex, phantom pain, deafferentation pain, postoperative neuralgia and an unclear allodynia of the foot. Mean pain intensity was reported as 4-6/10 on a numeric rating scale (NRS) and maximum pain intensity as 6-10/10. Pain reduction following ambroxol cream was 2-8 points (NRS) within 15-30 min and lasted 3-8 h. Pain attacks were reduced in all 5 patients presenting this problem. Topical ambroxol achieved pain reduction in 4 patients with no improvement after lidocaine 5% and 1 patient with no response to capsaicin 8%. No adverse events or skin changes have been observed, and the longest treatment duration is currently 4 years. CONCLUSION: Ambroxol acts as a strong local anesthetic and preferentially inhibits the nociceptive-relevant sodium channel subtype Nav 1.8. For the first time, we report relevant pain reduction following topical Ambroxol 20% cream in patients with neuropathic pain. Regarding the advantageous profile with rare side effects, the clinical benefit for pain patients should be further investigated.

[Capsaicin 8 % cutaneous patches for phantom limb pain. Results from everyday practice (non-interventional study)]. / Das 8 %ige Capsaicin-Pflaster bei Phantomschmerz. Ergebnisse aus dem Praxisalltag (nichtinterventionelle Studie).

BACKGROUND: Post amputation pain presents a challenge for pain physicians and is often detrimental to the patient's quality of life. PATIENTS AND METHODS: A prospective 12-week non-interventional study (NIS) was conducted in Germany to obtain data on the effectiveness and safety of capsaicin 8 % cutaneous patches from real life use in patients with peripheral neuropathic pain. For the first time in a subgroup of amputees data on post amputation pain were collected. This article presents the results for patients who suffered from phantom limb pain (PLP), stump pain (SP) and combined phantom limb/stump pain (PLP/SP). RESULTS: The analyses included 21 patients with post amputation pain (PLP: n = 10, SP: n = 4, PLP/SP: n = 7). The mean duration of pain (± standard deviation) was 12.8 ± 13.0 years for PLP, 23.1 ± 29.9 years for SP and 11.0 ± 15.8 years for PLP/SP. A single treatment with capsaicin 8 % cutaneous patches significantly reduced the average pain intensity over the observational period of 12 weeks. The mean numeric pain rating scale (NPRS) baseline score changed by - 2.4 for PLP with a standard error of the mean (SEM) of 0.4 (median: - 2.9, Q1: - 3.5, Q3: - 1.0), - 1.7 for SP (SEM: 0.8, median: - 1.1, Q1: - 2.9, Q3: - 0.5) and - 1.5 for PLP/SP (SEM: 0.6, median: - 2.0, Q1: - 2.3, Q3: 0) during weeks 1-12. The 30 % responder rates (i.e. ≥ 30 % reduction in pain, day 7/14 to week 12) were 70.0 % (PLP), 50.0 % (SP) and 28.6 % (PLP/SP). PLP and PLP/SP patients in particular, benefited from improvements in pain attacks, sleep duration and sleep quality and one patient (PLP/SP) reported an adverse drug reaction (increase of pain). Physicians rated the tolerability of the patch as very good or good in 90.5 % of patients. A poor tolerability was stated for none of the 21 amputees. Of the patients 80 % for PLP and 50 % for both SP and PLP/SP expressed the wish to receive retreatment with capsaicin 8 % patches. CONCLUSION: Capsaicin 8 % cutaneous patches seem to be effective and safe for the treatment of post amputation pain, notably in patients suffering from phantom limb pain.

[Prolonged-release tapentadol for phantom pain. A case series]. / Retardiertes Tapentadol bei Phantomschmerzen. Eine Fallserie.

OBJECTIVES: The successful therapy of phantom pain remains a major challenge, because the underlying pathophysiological mechanisms are still not fully understood. A therapeutic approach with tapentadol has not been described so far. PATIENTS AND METHODS: Five patients suffering upper and lower extremity phantom pain were successfully treated with tapentadol (prolonged release) with differing doses. RESULTS: In 4 patients, a strongly reduced pain intensity between 4 and 6.5 on the visual analog scale (VAS) was recorded. The fifth patient reported an increase in the nocturnal sleep duration from 2 to 5 h and a decrease in the number of phantom pain attacks by 30 %. In 2 patients, the additional medication could be lowered or stretched. Side effects (vertigo, fatigue) were only observed in one subject. CONCLUSION: The cases described provide preliminary evidence that the synergistic combination of µ-opioid receptor agonism (MOR) and noradrenalin re-uptake inhibition (NRI) provided by tapentadol may be beneficial in the treatment of phantom pain.

Mechanism- and experience-based strategies to optimize treatment response to the capsaicin 8% cutaneous patch in patients with localized neuropathic pain.

The capsaicin 8% cutaneous patch is an emergent new treatment option for patients with peripheral neuropathic pain. In randomized controlled clinical studies relevant pain relief for 12 weeks was achieved in about one third of patients following a single application. The first part of this paper is a review of the pathophysiology, pharmacology, and published clinical trials with the capsaicin 8% cutaneous patch. The second part reports on outcomes of an interdisciplinary expert workshop, where new treatment results of three major German pain centers were presented and reviewed with the objectives of obtaining responder rates for different pain syndromes, assessing maintenance of effect under real-life conditions, and giving recommendations for practical care. The 12 week responder rates with pain relief of ≥ 30% were comparable in patients with mononeuropathies (37.9%) and postherpetic neuralgia (38.8%). Similar responder rates were seen in a subgroup of patients with cervical spine radiculopathy and back pain (46.7%). In HIV-associated neuropathy the responder rates were high (47.8%) but lower in patients with other polyneuropathies (17.6%). Response rates were nearly identical after 1 week (46.6%) and 4 weeks (43.3) and dropped only slightly at 12 weeks (37.4%). In a subgroup of 54 patients who underwent a second treatment, efficacy was maintained. Response rates in patients with or without lidocaine pretreatment were comparable. Treatment with the capsaicin 8% cutaneous patch was generally safe and well tolerated. The workshop panel recommended further investigation of opportunities to improve the application procedure and to perform studies on the skin penetration and distribution of capsaicin. A modified quantitative sensory testing (QST) should be developed for clinical practice in order to better understand the correlation of sensory profiles and response to capsaicin treatment.

[Effect of botulinum toxin type B on residual limb sweating and pain. Is there a chance for indirect phantom pain reduction by improved prosthesis use?]. / Wirkung von Botulinumtoxin Typ B auf Stumpfschwitzen und Stumpfschmerzen. Besteht die Chance der indirekten Phantomschmerzreduktion durch bessere Prothesennutzung?

OBJECTIVES: Hyperhidrosis of a residual limb after amputation is one of the most common reasons for impaired prosthesis use and quality of life and affects 30-50% of all amputees causing skin irritation in about 25%. Thus the probability of residual limb pain increases in addition to an increased likelihood of phantom pain due to shorter duration of prothesis use. Development of both types of pain was studied following treatment of hyperhidrosis in 9 amputees. DESIGN: A total of 9 lower limb amputees received injections of 1750 units of botulinum toxin type B (BTX-B) for the treatment of hyperhidrosis of a residual limb (20 intracutaneous injections each). Prior to injections and 4 weeks and 3 months afterwards, patients rated the impairments regarding residual limb pain, phantom pain and sweating of the residual limb. Furthermore the duration of use of the prosthetic device and quality of life were rated on a numeric rating scale (NRS 0-10). RESULTS: Stump pain (n=9) was highly significantly reduced after 3 months (baseline: NRS 5; 4 weeks: NRS 4, p=0.109; 3 months: NRS 3, p=0.008) and also a tendency for phantom pain after 3 months (baseline NRS 5; 3 months: NRS 3; p=0.109). Sweating of the residual limb prior to BTX-B application was rated as a median 7 on the NRS scale with significant improvements after 4 weeks (NRS 3, p=0.027) and 3 months (NRS 3, p=0.020). Impaired duration of prothesis use improved from NRS 8 to NRS 2 (4 weeks; p=0.023) and NRS 3 (3 months; p=0.023) as well as the quality of life (p=0.016, p=0.023, respectively). CONCLUSIONS: Residual limb pain improved 3 months after intracutaneous, low-dose BTX-B in a trial with 9 patients and also phantom pain by tendency. Sweating of the residual limb was significantly reduced, probably thereby improving the duration of prothesis use. Larger studies should confirm these findings and conclusions.

[Lidocaine patch for therapy of neuropathic and non-neuropathic pain. A clinical case series of 87 patients]. / Lidocain-Pflaster zur Therapie neuropathischer und nichtneuropathischer Schmerzen. Klinische Fallstudie an 87 Patienten.

BACKGROUND: Topical lidocaine patches (LP) reduce pain in postherpetic neuralgia and other forms of focal neuropathy. The aim of this study was to determine clinical predictors of therapeutic success. MATERIAL AND METHODS: The medical histories of 87 patients with neuropathic (NS) and non-neuropathic pain (NNS) who had received LP as an add-on to their established pain medication were retrospectively analyzed. The variables assessed were gender, age, analgesic co-medication, pain localization, adverse effects and presence of dynamic allodynia. The impact of these variables on the clinical pain-relieving effect (scored on a 5-point scale) was investigated. RESULTS: A total of 24 out of 28 patients with manifest allodynia scored the therapy with LP as beneficial, patients without allodynia (n=59, 67.8%) profited significantly less frequently with only 39% (p<0.001). The probability of profiting from LP therapy in the presence of allodynia was found to be about tenfold higher compared to patients without allodynia (odds ratio 9.14). Of the 87 patients investigated 48 were female (55.2%). Allodynia was considerably more frequent in women (39.6%) compared to men (23.1%) but this was insignificant. Of the female patients 62.5% responded to LP treatment, compared to only 43.6% of men. In more than 60% of cases rated as very good pain relief allodynia was manifest and in non-responders only in less than 10%. The variables age, pain localization and analgesic co-medication were not related with the success of therapy. DISCUSSION: Patients with manifest allodynia profited significantly more frequently from LP therapy and were less frequently non-responders. Female patients showed therapeutic success more often together with a higher rate of allodynia. CONCLUSIONS: In the presence of allodynia, in especially of neuropathic origin, LP seems to be an effective and save option for add-on therapy, this being independent from pain localization and age. Gender specific effects however need more systematic investigation.

[Referred pain from amputation stump trigger points into the phantom limb]. / Auslösung von Phantomschmerzen und -sensationen durch muskuläre Stumpftriggerpunkte nach Beinamputationen.

OBJECTIVES: The aim of the study was to examine whether/how myofascial stump trigger points (TPs) after lower leg amputations are able to produce stump pain (SP), phantom pain (PP), and sensations (PS) in the phantom limb. METHODS: Palpation of the 5 most striking stump TPs of 30 leg amputees (12 transfemoral, 18 transtibial) was documented in a standardized manner. Patients were asked to localize SP, PP, and PS. RESULTS: Of 150 TPs, 14 produced involuntary stump movements and 10 stump fasciculations. Dorsal PP after ventral TP palpation occurred as well as PP in the toes from TPs near the hip. Of 30 patients, 20 reported PS and 8 PP; 60 of 150 TPs produced PS and 17 PP. Phantom phenomena were localized in 62.8% in the toes (1st toe 19.8%, toes 2-5 about 10% each), 17.9% midfoot, and the rest were more proximal. TPs were localized more in the lateral/dorsal stump than medial/ventral. About 70% of the TPs were found between 3 and 7 cm from the stump end, those with toe projections more distal than those with tibial projections. CONCLUSIONS: Myofascial TPs in amputation stumps are common and able to produce sensations and pain in the phantom limb. Most reported experiences were localized in the toes, as phantom pain usually is. There seems to be a "stump representation" and it seems possible that "referred TP pain" and "phantom pain" may develop from similar origin.