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Summary Background The limitations of current treatments for postherpetic neuralgia (PHN) have led to the investigation of localised, non-systemic alternatives. NGX-4010, a high-concentration (8%) capsaicin dermal patch, was developed to treat patients with neuropathic pain. We report the results of a randomised, double blind, 12-week study of the efficacy and safety of one application of NGX-4010 in patients with PHN. Methods In this multicentre, double-blind, parallel-group trial, 402 patients were randomly assigned to one 60-min application of NGX-4010 (640 μg/cm 2 [8% capsaicin]) or a low-concentration capsaicin control patch (3·2 μg/cm 2 [0·04% capsaicin]). Patients were aged 18–90 years, had had postherpetic neuralgia for at least 6 months, and had an average baseline numeric pain rating scale (NPRS) score of 3 to 9. The primary efficacy endpoint was percentage change in NPRS score from baseline to weeks two to eight. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00115310. Findings Patients who were randomly assigned to NGX-4010 (n=206) had a significantly greater reduction in pain during weeks two to eight than did patients who had the control patch (n=196). The mean changes in NPRS score were −29·6% vs −19·9% (difference −9·7%, 95% CI −15·47 to −3·95; p=0·001). 87 (42%) patients who received NGX-4010 and 63 (32%) controls had a 30% or greater reduction in mean NPRS score (odds ratio [OR] 1·56, 95% CI 1·03 to 2·37; p=0·03). The patients who had NGX-4010 had significant improvements in pain during weeks two to 12 (mean change in NPRS score −29·9% vs −20·4%, difference −9·5, −15·39 to −3·61; p=0·002). Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment, and short-lasting erythema and pain at the site of application were common, self-limited, and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls. Interpretation One 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia. No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain. Funding NeurogesX.

Context Postherpetic neuralgia (PHN) and painful human immunodeficiency virus-associated distal sensory polyneuropathy (HIV-DSP) are peripheral neuropathic pain syndromes that are difficult to treat. Current treatment options are often limited by poor tolerability. Objectives The objective of the current open-label study was to assess the safety of repeated applications of NGX-4010, a high-concentration capsaicin patch (capsaicin 8%), over one year, in patients with moderate to severe PHN or HIV-DSP. Methods Patients had successfully completed a previous NGX-4010 study and had a pain level appropriate for further treatment. Eligible patients had not been treated with NGX-4010 within 12 weeks of study initiation. Patients received pretreatment with a topical local anesthetic (lidocaine 4%) for 60 minutes followed by either a 60-minute (PHN and HIV-DSP patients) or a 90-minute (HIV-DSP patients) treatment with NGX-4010. Patients could receive up to three additional treatments at intervals of ≥12 weeks. Regardless of the number of treatments received, all patients were followed up for 48 weeks except for those withdrawing early. Results A total of 106 patients were enrolled and received a total of 293 NGX-4010 treatments. The most frequently reported treatment-emergent adverse events were transient, mild-to-moderate application site erythema, pain, edema, and papules. Small, transient pain-related increases in blood pressure during and immediately after NGX-4010 application were observed. There was no evidence of an increased incidence of adverse events, dermal irritation, intolerability, or impaired neurological function with repeated treatments. Conclusion It is concluded that repeated treatments with NGX-4010 administered over a one-year period are generally safe and well tolerated.

Pleistocene macaque remains are uncommon in Great Britain. In addition to three specimens previously known from three sites, four teeth from Hoxne, Suffolk are recorded here. Closely resembling teeth of modern Macaca sylvanus (Barbary ape), they were recovered from a Middle Pleistocene stratum containing stone artifacts (including handaxes) and fauna including cold-climate lemmings.