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Introduction Non-pharmacologic alternative therapies for pain have been around for a long time, some for hundreds of years. They have been used throughout history to treat many issues. Recent Findings Currently, alternative medicine is most frequently used to treat musculoskeletal pain, and between 59 and 90% of patients utilizing alternative therapies for chronic pain claimed they were helpful and can serve as an effective adjunctive for the treatment of chronic pain. Some examples of alternative therapies that will be discussed in this review include acupuncture, tai chi, osteopathic manipulation, and chiropractic care. Acupuncture, traditionally a Chinese practice, is becoming more popular across the world to attempt to relieve pain. It involves the placement of thin needles at various points in the body. The efficacy of acupuncture for pain is heavily debated. More research and discussion are necessary to determine the exact role it plays in the treatment of chronic pain. Tai chi is also a traditional Chinese practice that is often used as a form of meditation and for potential health benefits. Tai chi involves a series of complex movements such as squatting combined with deep breathing to achieve relaxation and pain reduction. Osteopathic manipulative treatment (OMT) is a technique used by both osteopathic physicians (DO) as well as other health professionals to manage a wide range of conditions in any given patient. The technique involves utilization and manipulation of the musculoskeletal system to achieve potential health benefits. OMT has been used as therapy for many issues but is commonly used for pain conditions. Summary Alternative therapies may serve as an effective adjunctive treatment modality for the management of chronic pain conditions. There has been a tremendous amount of research dictating the effectiveness of alternative therapies for chronic pain management. The purpose of this review is to provide a comprehensive evidence-based update of alternative therapy used for the management of chronic pain conditions.

Occipital neuralgia (ON) is unilateral or bilateral neuralgia in the dermatomal nerve distribution of the greater, lesser or third occipital nerves and is a very common presentation of

Context: Neuromodulation is an expanding field of study for headache treatment to reduce pain by targeting structures within the nervous system commonly involved in headache pathophysiology, such as the vagus nerve (VNS), occipital nerves, or sphenopalatine ganglion (SPG) for stimulation. Pharmaceutical medical therapies for abortive and prophylactic treatment, such as triptans, NSAIDs, beta-blockers, TCAs, and antiepileptics, are effective for some individuals, but the role that technology plays in investigating other therapeutic modalities is essential. Peripheral neuromodulation has gained popularity and FDA approval for use in treating certain headaches and migraine headache conditions, particularly in those who are refractory to treatment. Early trials found FDA approved neurostimulatory implant devices, including Cephaly and SpringTMS, improved patient-oriented outcomes with reductions in headaches per month (frequency) and severity. Evidence Acquisition: This was a narrative review. The sources for this review are as follows: Searching on PubMed, Google Scholar, Medline, and ScienceDirect from 1990 - 2019 using keywords: Peripheral Neuromodulation, Headache, vagus nerve, occipital nerves, sphenopalatine ganglion. Results: The first noninvasive neurostimulator device approved for migraine treatment was the Cefaly device, an external trigeminal nerve stimulation device (e-TNS) that transcutaneously excites the supratrochlear and supraorbital branches of the ophthalmic nerve. The second noninvasive neurostimulation device receiving FDA approval was the single-pulse transcranial magnetic stimulator, SpringTMS, positioned at the occiput to treat migraine with aura. GammaCore is a handheld transcutaneous vagal nerve stimulator applied directly to the neck at home by the patient for treatment of cluster headache (CH) and migraine. Several other devices are in development for the treatment of headaches and target headache evolution at different levels and inputs. The Scion device is a caloric vestibular stimulator (CVS) which interfaces with the user through a set of small cones resting in the ear canal on either side and held in place by modified over-ear headphones. The pulsante SPG Microstimulator is a patient-controlled device implanted in the patient’s upper jaw via an hour-long oral procedure to target the sphenopalatine ganglion. The occipital nerve stimulator (ONS) is an invasive neuromodulation device for headache treatment that consists of an implanted pulse generator on the chest wall connected to a subcutaneous lead with 4 - 8 electrodes that is tunneled the occiput. Conclusions: The aim of this review is to provide a comprehensive overview of the efficacy, preliminary outcomes, and limitations of neurostimulatory implants available for use in the US and those pending further development.

The Murine Double Minute 2 (MDM2) amplification or overexpression has been found in many tumors with high metastatic and angiogenic ability. Our experiments were designed to explore the impact of MDM2 overexpression, specifically on the levels of angiogenesis-related genes, which can also play a major role in tumor propagation and increase its metastatic potential. In the present study, we have used the human angiogenesis RT2 profiler PCR array to compare the gene expression profile between LNCaP and LNCaP-MST (MDM2 transfected) prostate cancer cells, along with LNCaP-MST cells treated with Nutlin-3, an MDM2 specific inhibitor. As a result of the overexpression of MDM2 gene in LNCaP-MST (10.3-fold), Thrombospondin 1 (THBS1), Tumor necrosis factor alpha (TNF-α) and Matrix metallopeptidase 9 (MMP9) were also found to be significantly up-regulated while genes such as Epiregulin (EREG), Tissue inhibitor of metalloproteinases 1 (TIMP1) were down-regulated. Also, we determined the total MMP activity and MMP9 expression in LNCaP, LNCaP-MST and SJSA-1 cells. Our results indicated that MDM2 level is positively correlated with MMP activity and MMP9 secretion. Our findings offer strong supporting evidence that MDM2 can impact growth and metastatic potential of cancer cells through tilting the balance towards pro-angiogenic mechanisms.

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