BACKGROUND: This 52-week study evaluated the long-term safety and tolerability of capsaicin 8% w/w (179 mg) patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy (PDPN). METHODS: Phase 3, multinational, open-label, randomised, controlled, 52-week safety study, conducted in Europe. Patients were randomised to capsaicin 8% patch repeat treatment (30 or 60 min; 1-7 treatments with ≥ 8-week intervals) to painful areas of the feet plus SOC, or SOC alone. The primary objective was the safety of capsaicin 8% patch repeat treatment (30 min and 60 min applications) plus SOC versus SOC alone over 52 weeks, assessed by changes in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) total score from baseline to end of study (EOS). Secondary safety endpoints included Utah Early Neuropathy Scale (UENS) assessments and standardised testing of sensory perception and reflex function. RESULTS: Overall, 468 patients were randomised (30 min plus SOC, n = 156; 60 min plus SOC, n = 157; SOC alone, n = 155). By EoS, mean changes in Norfolk QOL-DN total score from baseline [estimated mean difference versus SOC alone; 90% CI for difference] were: 30 min plus SOC, -27.6% [-20.9; -31.7, -10.1]; 60 min plus SOC, -32.8% [-26.1; -36.8, -15.4]; SOC alone, -6.7%. Mean changes [difference versus SOC alone] in UENS total score by EoS versus baseline were: 30 min plus SOC, -2.1 [-0.9; -1.8, 0.1]; 60 min plus SOC, -3.0 [-1.7; -2.7, -0.8]; SOC alone, -1.2. No detrimental deterioration was observed in any of the Norfolk or UENS subscales by EoS with capsaicin. Also, no worsening in sensory perception testing of sharp, warm, cold and vibration stimuli was found with capsaicin by EoS. Capsaicin treatment was well tolerated and the most frequent treatment-emergent adverse events were application site pain (30 min, 28.2%; 60 min, 29.3%), burning sensation (30 min, 9.0%; 60 min, 9.6%) and application site erythema (30 min, 7.7%; 60 min, 8.9%). CONCLUSION: In patients with PDPN, capsaicin 8% patch repeat treatment plus SOC over 52 weeks was well tolerated with no negative functional or neurological effects compared with SOC alone. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT01478607 . Date of registration November 21, 2011; retrospectively registered.

• MeSH
• aplikace kožní MeSH
• diabetické neuropatie komplikace   farmakoterapie   MeSH
• dospělí MeSH
• hodnocení výsledků zdravotní péče * MeSH
• kapsaicin aplikace a dávkování   škodlivé účinky   MeSH
• látky ovlivňující senzorický systém aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neuralgie farmakoterapie   etiologie   MeSH
• senioři MeSH
• standardní péče * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Allodynia and hyperalgesia present after surgical interventions are often a major complain of surgical patients. It is thought that both peripheral and central mechanisms contribute to these symptoms. In this study, the role of peripheral nerve fibres that express transient receptor potential vanilloid 1 (TRPV1) receptors in the activation of spinothalamic tract (STT) and postsynaptic dorsal column (PSDC) neurons was assessed in a model of surgical pain. METHODS: Spinothalamic tract and PSDC neurons retrogradely labelled from the thalamus and nucleus gracilis were used. Activation of these projection neurons was evaluated after plantar incision as expression of the early gene product, c-Fos protein, in the nuclei of these neurons. RESULTS: There was a robust increase in c-Fos immunopositivity in the STT and PSDC neurons, in the control animals after a plantar incision. This increase in c-Fos expression was significantly attenuated in animals in which a single high-concentration capsaicin injection was made intradermally at the incision site 24 h before the surgery. CONCLUSIONS: Our results suggest that activation of both STT and PSDC neurons is involved in development of pain states present after surgical incision and that TRPV1-containing peripheral nerve fibres are needed for c-Fos expression in these dorsal horn neurons after plantar incision.

• MeSH
• buňky zadních rohů míšních metabolismus   MeSH
• kapsaicin aplikace a dávkování   farmakologie   MeSH
• kationtové kanály TRPV metabolismus   MeSH
• krysa rodu rattus MeSH
• látky ovlivňující senzorický systém aplikace a dávkování   farmakologie   MeSH
• medulla oblongata metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nervová vlákna * účinky léků   metabolismus   MeSH
• pooperační bolest * farmakoterapie   etiologie   metabolismus   MeSH
• potkani Wistar MeSH
• protoonkogenní proteiny c-fos účinky léků   metabolismus   MeSH
• tractus spinothalamicus účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH