A review on ultrasonic neuromodulation of the peripheral nervous system: enhanced or suppressed activities?

Ultrasonic (US) neuromodulation has emerged as a promising therapeutic means by delivering focused energy deep into the tissue. Low-intensity ultrasound (US) directly activates and/or inhibits neurons in the central nervous system (CNS). US neuromodulation of the peripheral nervous system (PNS) is less developed and rarely used clinically. Literature on the neuromodulatory effects of US on the PNS is controversy with some documenting enhanced neural activities, some showing suppressed activities, and others reporting mixed effects. US, with different range of intensity and strength, is likely to generate distinct physical effects in the stimulated neuronal tissues, which underlies different experimental outcomes in the literature. In this review, we summarize all the major reports that documented the effects of US on peripheral nerve endings, axons, and/or somata in the dorsal root ganglion. In particular, we thoroughly discuss the potential impacts by the following key parameters to the study outcomes of PNS neuromodulation by the US: frequency, pulse repetition frequency, duty cycle, intensity, metrics for peripheral neural activities, and type of biological preparations used in the studies. Potential mechanisms of peripheral US neuromodulation are summarized to provide a plausible interpretation to the seemly contradictory effects of enhanced and suppressed neural activities from US neuromodulation.

Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article.

CONTEXT: Visceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also target the periphery with minimal CNS effects. EVIDENCE OF ACQUISITION: In this paper, reputable internet databases from 1960 - 2016 were searched including Pubmed and ClinicalTrials.org, and 97 original articles analyzed. Search was performed based on the following keywords and combinations: irritable bowel syndrome, clinical trial, pain, visceral pain, narcotics, opioid, chloride channel, neuropathy, primary afferent, intestine, microbiota, gut barrier, inflammation, diarrhea, constipation, serotonin, visceral hypersensitivity, nociceptor, sensitization, hyperalgesia. RESULTS: Certain conventional pain managing drugs do not effectively improve IBS symptoms, including NSAIDs, acetaminophen, aspirin, and various narcotics. Anxiolytic and antidepressant drugs (Benzodiazepines, TCAs, SSRI and SNRI) can attenuate pain in IBS patients with relevant comorbidities. Clonidine, gabapentin and pregabalin can moderately improve IBS symptoms. Lubiprostone relieves constipation predominant IBS (IBS-C) while loperamide improves diarrhea predominant IBS (IBS-D). Alosetron, granisetron and ondansetron can generally treat pain in IBS-D patients, of which alosetron needs to be used with caution due to cardiovascular toxicity. The optimal drugs for managing pain in IBS-D and IBS-C appear to be eluxadoline and linaclotide, respectively, both of which target peripheral GI tract. CONCLUSIONS: Conventional pain managing drugs are in general not suitable for treating IBS pain. Medications that target the GI tract and peripheral nerves have better therapeutic profiles by limiting adverse CNS effects.