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V Mazzarello, MG Donadu, M Ferrari, G Piga, D Usai, S Zanetti, MA Sotgiu Skinlab, Department of Biomedical Sciences, University of Sassari, Sassari, Italy Introduction: Antibiotics that suppress Propionibacterium acnes are the standard treatment for acne but are becoming less effective, due to the appearance of antibiotic-resistant strains. Many plants are known to have innate antimicrobial action and can be used as alternatives to antibiotics; thus, it is necessary to prove their effectiveness in vivo. This study aimed to evaluate the anti-acne efficacy of a new cream based on three natural extracts, comparing it to erythromycin cream and placebo. Patients and methods: Sixty patients with mild to moderate acne vulgaris were randomly divided into three groups: treated with cream containing 20% propolis, 3% “tea tree oil”, and 10% “Aloe vera” (PTAC) (n=20); or with 3% erythromycin cream (ERC) (n=20); or with placebo (n=20). At baseline, after 15 and 30 days, investigators evaluated response to treatment by counting acne lesions through noninvasive measurements and macro-photography. Results: All the clinical and instrumental values studied were statistically different from placebo except for sebometry, pHmetry, and erythema index values, measured on healthy skin. Unlike in the placebo group, papular and scar lesions showed high erythema reduction after 15 and 30 days of PTAC and ERC application. Conclusion: The PTAC formulation was better than ERC in reducing erythema scars, acne severity index, and total lesion count. Keywords: phytotherapy, Aloe barbadensis, Melaleuca alternifolia oil, propolis, noninvasive analysis, antibiotic resistance

An attractive alternative to the use of direct agonists at the cannabinoid receptor type 1 (CB1) in the control of neuropathic pain may be to potentiate the actions of endogenous cannabinoids. Thus, the effects of AM404, an inhibitor of anandamide uptake, were assessed in an experimental model of neuropathic pain in rats. Daily treatment with AM404 prevented, time- and dose-dependently, the development of thermal hyperalgesia and mechanical allodynia in neuropathic rats. Antagonists at cannabinoid CB1 or CB2 receptors, or at the transient receptor potential vanilloid type 1 receptor, each partially reversed effects induced by AM404. A complete reversal was obtained when the three antagonists were given together, suggesting that all three receptors are involved. AM404 treatment affected two pathways involved in the generation and maintenance of neuropathic pain, one mediated by nitric oxide (NO) and the other by cytokines. AM404 completely prevented the overproduction of NO and the overexpression of nNOS, inhibited the increase in tumour necrosis factor alpha (TNFalpha) and enhanced the production of interleukin-10. Both NO and TNFalpha are known to contribute to the apoptotic process, which plays an important role in the establishment of chronic pain states. AM404 treatment prevented the increase in the ratio between pro- and anti-apoptotic gene bax/bcl-2 expression observed in the spinal cord of neuropathic rats. Taken together, these findings suggest that inhibition of endocannabinoid uptake, by blocking the putative anandamide carrier, results in the relief of neuropathic pain and may represent a novel strategy for treating chronic pain.

The antinociceptive properties of cannabinoids in persistent pain are not fully elucidated. We investigated the effect of repeated treatment with the synthetic cannabinoid receptor agonist WIN 55,212-2 on the neuropathic pain induced in rats by chronic constriction of the sciatic nerve. WIN 55,212-2 administered daily throughout the development of neuropathy reversed the hyperalgesia, at a dose (0.1 mg x kg(-1), s.c.) that had no effect on the nociceptive responses of either paw contralateral to the sciatic ligation or of animals subjected to sham surgery. At 14 days after injury, the levels of mediators known to be involved in neuropathic pain, such as prostaglandin E2, NO and the neuronal NOS, were increased. Repeated treatment with WIN 55,212-2 abolished these increases. In the light of the current clinical need for neuropathic pain treatments, these findings indicate that cannabinoid agonists, at doses devoid of psychoactive effects, could constitute important compounds for the development of new analgesics.

Acupuncture is largely used for pain control in several pathological conditions. Its effects on the central nervous system are not well defined. We investigated the effect of the application of acupuncture to 13 normal subjects (males, 21-32 years). (H2O)-O-15 bolus PET scans were read before the application of the needles (Rest, R) and after 25 min of needle insertion. Data were acquired by scanning in 3-D mode. The acupuncture application, true acupuncture (TA), was alternated to a placebo needle application (PA) in two:different sequences (seven and six subjects, respectively), either R,PA,R, TA or R,TA,R,PA, a period of 15 min being left after every first TA or PA to allow for the recovery of basal conditions. Here we show that classic acupuncture activates the left Anterior Cingulus, the Insulae bilaterally, the Cerebellum bilaterally, the left Superior Frontal Gyrus, and the right Medial and Inferior Frontal Gyri. Most of the activated areas are shared with areas activated in acute and chronic pain states as described in the literature. Thus acupuncture appears to act by activating areas also involved in pain. This indicates that acupuncture could relief pain by unbalancing the equilibrium of distributed pain-related central networks