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.

[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.

Treatment of peripheral neuropathic pain by topical capsaicin: Impact of pre-existing pain in the QUEPP-study.

BACKGROUND: This study evaluates the impact of the duration of pre-existing peripheral neuropathic pain on the therapeutic response to the capsaicin 8% cutaneous patch. METHODS: The non-interventional QUEPP (QUTENZA - safety and effectiveness in peripheral neuropathic pain) study evaluated the effectiveness of Qutenza(TM) in 1044 non-diabetic patients with peripheral neuropathic pain, who received a single application. Follow-up visits were scheduled at weeks 1-2, 4, 8 and 12. A pre-defined co-analysis of changes in average pain intensity was performed based on the duration of pre-existing pain. RESULTS: In patients with pre-existing pain for <6 months, the mean relative change of the numeric pain rating scale score on days 7-14 to week 12 versus baseline was -36.6% [4.6 standard error of the mean (SEM); n = 105], -25.1% (1.9 SEM; n = 311) in patients with pain duration of 6 months to 2 years, -22.3% (1.6 SEM; n = 391) in patients with pain for >2-10 years, and -19.2% (2.6 SEM; n = 99) in patients with pain for >10 years. Thirty percent and 50% responder rates were 61.7% and 39.3% in patients with pre-existing pain for <6 months, 42.3% and 23.3% in patients with pain for 6 months to 2 years, 40.9% and 21.6% in patients with pain for >2-10 years, and 32.3% and 14.1% in patients with pain for >10 years. CONCLUSIONS: The highest treatment response to the capsaicin 8% cutaneous patch was observed in patients with a history of pre-existing peripheral neuropathic pain of less than 6 months, suggesting that early initiation of topical treatment might be indicated.

Prospective, non-interventional study on the tolerability and analgesic effectiveness over 12 weeks after a single application of capsaicin 8% cutaneous patch in 1044 patients with peripheral neuropathic pain: first results of the QUEPP study.

BACKGROUND: Reversible defunctionalisation of nociceptors by the TRPV1 agonist capsaicin in high concentration is an emerging new concept for the treatment of peripheral neuropathic pain. OBJECTIVES: The capsaicin 8% cutaneous patch with a long-lasting effect for up to 3 months after a single application is available in Germany by prescription since October 2010. The aim of this study was to monitor its usage and therapeutic performance in clinical practice. METHODS: Patients had a single patch application with up to 4 patches and were followed up after 7-14 days, 4, 8, and 12 weeks. Average pain intensity (NPRS-11), pain attacks, neuropathy symptoms, sleep parameters, quality of life, working capacity and concomitant neuropathic pain medication were assessed during at least two visits. RESULTS: A total of 509 females (48.8%; effectiveness population N = 1044) and 531 males (50.9%) were included; the mean age was 61.2 ± 14.4 (SD) years. Postherpetic neuralgia was the most frequent diagnosis (31.9%), followed by postsurgical neuralgia (22.8%), post-traumatic neuropathy (12.4%), polyneuropathy (14.3%), and mixed pain syndromes (16.6%). Thirty and 50% responder rates were 42.7% and 23.7%, respectively, with a mean relative reduction of pain intensity during weeks 1-12 of 24.7% (1.1 SEM) and significant improvements in pain attacks, sleep duration and sleep quality, while the consumption of opioids and antiepileptics decreased significantly. In 106 patients (10.0%; safety population n = 1063) 146 adverse drug reactions (ADRs) were reported, mainly application site reactions (erythema, pain). A total of 27 serious ADRs were documented in 17 patients (1.6%). CONCLUSIONS: Analgesic treatment of peripheral neuropathic pain with the capsaicin 8% cutaneous patch is safe and effective. LIMITATIONS: The study did not include a control group; therefore, a comparison of the results with that of therapeutic alternatives is not justified.

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.

Purification and antigenicity of flavone synthase I from irradiated parsley cells.

Flavone synthase I, a soluble 2-oxoglutarate-dependent dioxygenase catalyzing the oxidation of flavanones to flavones in several Apiaceae species, was induced in parsley cell cultures by continuous irradiation with ultraviolet/blue light for 20 h. The enzyme was extracted from these cells and purified by a revised purification protocol including the fractionation on hydroxyapatite, Fractogel EMD DEAE, and Mono Q anion exchangers, which resulted in an apparently homogeneous flavone synthase at approximately 10-fold higher yield as compared to the previous report. The homogeneous enzyme was employed to raise an antiserum in rabbit for partial immunological characterization. The specificity of the polyclonal antibodies was demonstrated by immunotitration and Western blotting of the crude ammonium sulfate-fractionated enzyme as well as of the enzyme at various stages of the purification. High titer cross-reactivity was observed toward flavone synthase I, showing two bands in the crude extract corresponding to molecular weights of 44 and 41 kDa, respectively, while only the 41 kDa was detected on further purification. The polyclonal antiserum did not cross-react with recombinantly expressed flavanone 3beta-hydroxylase from Petunia hybrida or flavonol synthase from Citrus unshiu, two related 2-oxoglutarate-dependent dioxygenases involved in the flavonoid pathway.