The Utility of Capsicum annuum L. in Internal Medicine and In Dentistry: A Comprehensive Review.

Capsaicin is a chili peppers extract, genus Capsicum, commonly used as a food spice. Since ancient times, Capsaicin has been used as a "homeopathic remedy" for treating a wild range of pathological conditions but without any scientific knowledge about its action. Several studies have demonstrated its potentiality in cardiovascular, nephrological, nutritional, and other medical fields. Capsaicin exerts its actions thanks to the bond with transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is a nociceptive receptor, and its activation starts with a neurosensitive impulse, responsible for a burning pain sensation. However, constant local application of Capsaicin desensitized neuronal cells and leads to relief from neuropathic pain. In this review, we analyze the potential adjuvant role of Capsaicin in the treatment of different pathological conditions either in internal medicine or dentistry. Moreover, we present our experience in five patients affected by oro-facial pain consequent to post-traumatic trigeminal neuropathy, not responsive to any remedy, and successfully treated with topical application of Capsaicin. The topical application of Capsaicin is safe, effective, and quite tolerated by patients. For these reasons, in addition to the already-proven beneficial actions in the internal field, it represents a promising method for the treatment of neuropathic oral diseases.

Identifying and managing CAR T-cell-mediated toxicities: on behalf of an Italian CAR-T multidisciplinary team.

INTRODUCTION: Chimeric antigen receptor (CAR)-T-cell therapy is a new treatment for patients with hematologic malignancies in which other therapies have failed. AREAS COVERED: The review provides an overview for recognizing and managing the most acute toxicities related to CAR-T cells. EXPERT OPINION: The development of immune-mediated toxicities is a common challenge of CAR-T therapy. The mechanism that determines this toxicity is still unclear, although an unfavorable tumor microenvironment and a pro-inflammatory state put patients at risk. The monitoring, diagnosis, and treatment of post-CAR-T toxicities must be determined and based on international guidelines and internal clinical practice. It is urgent to identify biomarkers that can identify patients at greater risk of developing complications. The adoption of consistent grading criteria is necessary to improve toxicity management strategies continually. The first-line therapy consists of supportive care and treatment with tocilizumab or corticosteroids. An early start of cytokine blockade therapies could mitigate toxicity. The plan will include cytokine release prophylaxis, a risk-adapted treatment, prevention of on-target/off-tumor effect, and a switch on/off CAR-T approach.

Post-Mastectomy Pain: An Updated Overview on Risk Factors, Predictors, and Markers.

After breast surgery, women frequently develop chronic post-mastectomy pain (PMP). PMP refers to the occurrence of pain in and around the area of the mastectomy lasting beyond three months after surgery. The nature of factors leading to PMP is not well known. When PMP is refractory to analgesic treatment, it negatively impacts the lives of patients, increasing emotional stress and disability. For this reason, optimizing the quality of life of patients treated for this pathology has gained more importance. On the basis of the findings and opinions above, we present an overview of risk factors and predictors to be used as potential biomarkers in the personalized management of individual PMP. For this overview, we discuss scientific articles published in peer-reviewed journals written in the English language describing risk factors, predictors, and potential biomarkers associated with chronic pain after breast surgery. Our overview confirms that the identification of women at risk for PMP is fundamental to setting up the best treatment to prevent this outcome. Clinical practice can be planned through the interpretation of genotyping data, choosing drugs, and tailoring doses for each patient with the aim to provide safer and more effective individual analgesic treatment.

Pain Biomarkers in Cancer: An Overview.

BACKGROUND: Pain is a common symptom in oncologic patients and its management is generally guided with reference to pain individually perceived by patients and expressed through self-reported scales. However, the utility of these tools is limited as it strongly depends on patients' opinions. For this reason, more objective instruments are desirable. OBJECTIVE: In this overview, scientific articles indicating potential markers to be used for pain management in cancer were collected and discussed. METHODS: Research was performed on principal electronic scientific databases by using the words "pain", "cancer", "markers" and "biomarkers" as the main keywords, and findings describing potential biomarkers for the management of cancer pain were reported. RESULTS: Studies on pain markers not specific for cancer typology (inflammatory, genetic markers predicting response to analgesic drugs, neuroimaging markers) and pain markers for specific types of cancer (bone cancer, breast cancer, lung cancer, head and neck cancer, prostate cancer, cancer in pediatrics) have been presented and commented on. CONCLUSION: This overview supports the view of the involvement of inflammatory mediators in the mechanisms underlying cancer pain. Only a small amount of data from research up till today is available on markers that can help in the management of pain, except for pro-inflammatory cytokines and other inflammatory indexes such as C-reactive protein (CRP). However, biomarkers are a promising strategy useful to predict pain intensity and to objectively quantify analgesic response in guiding decisions regarding individual-tailored treatments for cancer patients.

Clinical use of omega-3 fatty acids in migraine: A narrative review.

BACKGROUND: Omega-3 fatty acids (FAs) can produce several beneficial effects and are commonly used for the treatment of migraine symptoms. Although current therapeutic measures for migraine included pharmacological therapies, dietary supplements, and herbal ingredients, dietary patterns, acupuncture, relaxation techniques, biofeedback, and psychotherapy, omega-3 FAs therapeutic role seems to be obtained through the inhibition or reduction of the release of inflammatory cytokines. The present review aims to provide updated information about the effects of omega-3 FAs in migraine treatment, investigating their clinical effects alone or in combination with other substances. METHODS: Bibliographic research was conducted by examining scientific literature from January 2000 until January 31, 2020. Ten clinical studies were included in the review. Quality assessment of randomized controlled trials was performed by using the JADAD scale. RESULTS: Clinical studies methodology is not always of good quality and results show moderate evidence concerning the therapeutic role of omega-3 FAs in migraine. CONCLUSION: Further clinical trials are necessary to implement the knowledge concerning the use of omega-3 fatty acids in the treatment of migraine.

Preclinical and Clinical Pharmacology of Hydrocodone for Chronic Pain: A Mini Review.

Hydrocodone is one of the most prescribed oral analgesic drugs and it is one of the most abused drugs in general population. It is a mu-opioid agonist predominantly metabolized to the O-demethylated product hydromorphone and to the N-demethylated product norhydrocodone. The purpose of the study is to summarize the preclinical and clinical characteristics of hydrocodone. Pharmacokinetic aspect (terminal half-life, maximum serum concentration, and time to maximum serum concentration) of hydrocodone and the influence of metabolic genetic polymorphism in analgesic response to hydrocodone are also illustrated and commented. Literature on experimental preclinical pharmacology investigating analgesic activity in laboratory animals is furtherly discussed. Moreover, the authors discuss and comment on the updated data regarding safety profile and effectiveness of hydrocodone in the treatment of chronic pain. A bibliographic research was carried out (from February 01, 2018 to August 28, 2018) independently by two researchers (blinded to the authors and initially on results) in the major scientific databases and research engines of peer-reviewed literature on life sciences and biomedical topics, starting from January 1990 to August 2018. Analysis of results of clinical studies suggests that abuse-deterrent extended-release (ER) hydrocodone formulations can be effective and they are well tolerated in the treatment of chronic low back pain. Weaker is the evidence of the analgesic effectiveness of ER hydrocodone on other chronic pain syndromes and non-cancer non-neuropathic chronic pain. In these conditions, hydrocodone showed to have positive effects in non-controlled open studies and needs to be further studied to assess the real strength of results.

Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain.

OBJECTIVE: This study aimed to evaluate pain and its symptoms in patients with failed back surgery syndrome (FBSS) refractory to other therapies, treated with a combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in association with spinal cord stimulation (SCS). SETTINGS: Outpatients referred at Pain Unit of San Vincenzo Hospital in Taormina (Italy), between September 2014 and January 2016. SUBJECTS: Eleven FBSS patients diagnosed with neuropathic pain using the Douleur Neuropathique 4 questionnaire and suffering from moderate to severe chronic refractory pain, and undergoing treatment with SCS and a combination of THC/CBD for 12 consecutive months. MATERIALS AND METHODS: All the included patients discontinued previous unsuccessful therapy at least 2 months before the beginning of the cannabinoid therapy, with the exception of the SCS that was continued. Patients received a fixed dosage of cannabinoid agonists (THC/CBD) that could be increased subjective to pain control response. A Brief Pain Inventory questionnaire was administered to measure pain and its interference with characteristic dimensions of feelings and functions. The duration of treatment with SCS and THC/CBD combination was 12 months. RESULTS: Effective pain management as compared to baseline result was achieved in all the cases studied. The positive effect of cannabinoid agonists on refractory pain was maintained during the entire duration of treatment with minimal dosage titration. Pain perception, evaluated through numeric rating scale, decreased from a baseline mean value of 8.18±1.07-4.72±0.9 by the end of the study duration (12 months) (P<0.001). CONCLUSION: The results indicate that cannabinoid agonists (THC/CBD) can have remarkable analgesic capabilities, as adjuvant of SCS, for the treatment of chronic refractory pain of FBSS patients.