Pharmacologic and Non-Pharmacologic Interventions for HIV-Neuropathy Pain. A Systematic Review and a Meta-Analysis.

Background and Objectives: Among HIV infection symptoms, sensory neuropathy (HIV-SN) remains a main cause of suffering, with incidence varying from 13-50%. So far, numerous pharmacological and non-pharmacological treatments have been tested, although few evidence-based analgesic options are available. We conducted an up-to-date systematic review and meta-analysis of the literature in order to evaluate the efficacy and safety of pharmacologic and non-pharmacologic treatments for pain control, in patients with HIV neuropathy. Materials and Methods: We searched MEDLINE, EMBASE, Scopus/Elsevier, The Cochrane Central Register of Controlled Trials (CENTRAL), USA Clinical Trials registry, and The International Web of Science up to April 2019. All randomized controlled trials evaluating efficacy and safety of non-pharmacologic and pharmacologic therapies were included. Efficacy was defined as pain reduction during the study period. Safety was estimated from adverse events. A meta-analysis was performed whenever possible. Results: 27 randomized controlled trials (RCTs) were included for analysis (7 evaluating non pharmacologic interventions, 20 pharmacologic therapies). Non-pharmacologic studies (n = 742) involved seven different therapeutic modalities. Only Acupuncture/Moxibustion showed pain reduction over placebo, Gracely Pain Scale Mean (SD): Acu/Moxa 0.85 (0.12), placebo 1.10 (0.09), p = 0.05. Pharmacologic studies, involving 2516 patients revealed efficacy for capsaicin 8% over placebo (mean difference -8.04 [95% CI: -14.92 -1.15], smoked cannabis (where pooling data for meta-analysis was not possible) and recombinant Nerve Growth Factor. Conclusion: Despite various modalities for pain control in HIV-SN, strongest evidence exists for capsaicin 8% and smoked cannabis, although of low methodological quality. Among non-pharmacologic modalities, only Acu/Moxa gave a marginal beneficial effect in one study, possibly limited by inherent methodological flaws.

Combined Enteral and Parenteral Glutamine Supplementation in Endotoxemic Swine: Effects on Portal and Systemic Circulation Levels.

OBJECTIVE: To measure plasma glutamine (GLN) levels in systemic and portal circulation after combined enteral and parenteral administration in early endotoxemic swine. We hypothesized that this combination will be more efficient than intravenous administration alone in restoring plasma levels during the course of endotoxemia. MATERIALS AND METHODS: Endotoxemia was induced with Escherichia coli O111:B4 lipopolysaccharide (LPS) (250 µg/kg body weight) in 16 anes-thetized, fasted swine and maintained by constant infusion (2 µg/kg/h) over 180 min. Another 16 swine served as controls. After infusion with LPS or placebo, GLN was administered intravenously, enterally or in combination (0.5 g/kg i.v. plus 0.5 g/kg enterally) over 30 min. At 0, 15, 30, 45, 60, 120 and 180 min, blood was drawn from the systemic and portal circulation for colorimetric assessment of GLN. RESULTS: In healthy, placebo-alone swine, GLN levels remained stable throughout the study. Intravenous and combined infusion increased systemic levels (p = 0.001), but after enteral administration alone, a smaller effect was observed (p = 0.026). Portal levels were increased after combined, enteral and intravenous administration (p = 0.001). In endotoxemia, systemic and portal levels decreased significantly. Intravenous and, to a greater extent, combined administration increased systemic levels (p = 0.001), while enteral administration only had a small effect (p = 0.001). In the portal vein, intravenous and combined treatment increased plasma levels (p = 0.001), whereas enteral supplementation alone had again a small, yet significant effect (p = 0.001). CONCLUSIONS: The findings indicate that combined GLN supplementation is superior to intravenous treatment alone, in terms of enhanced availability in systemic and portal circulations. Thus, combined treatment at the onset of endotoxemia is a beneficial practice, ensuring adequate GLN to compensate for the resulting intracellular shortage.

Subcutaneous targeted neuromodulation technique for the treatment of intractable chronic postthoracotomy pain.

Subcutaneous targeted neuromodulation has been used successfully in chronic neuropathic pain. A 26 year-old patient with severe postthoracotomy pain and ipsilateral "wing scapula" due to intraoperative injury of the long thoracic nerve, is reported. Application of targeted neuromodulation resulted in immediate pain relief and marked improvement of shoulder function at one-year follow-up. The technique may be an effective alternative treatment of chronic and intractable postoperative painful conditions.