UNASSIGNED: Visceral pain, characterized by pain that is diffuse and challenging to localize, occurs frequently and is difficult to treat. In cases where the pain becomes intractable despite optimal medical management, it can affect patients\' Quality of Life (QoL). Spinal Cord Stimulation (SCS) has emerged as a potential solution for intractable visceral pain.
UNASSIGNED: In this narrative review, we collected all evidence regarding the efficacy of SCS for visceral pain across various underlying conditions.
UNASSIGNED: A comprehensive literature search was conducted in PubMed, Embase, and Web of Science in which articles published from October 1st, 1963 up to March 7th, 2023 were identified.
UNASSIGNED: Seventy articles were included in this review of which most were retrospective cohort studies, case series and case reports. The studies, often with a small number of participants, reported on SCS for chronic pancreatitis, anorectal pain and bowel disorders, gynaecological diagnoses, visceral pelvic pain, urological disorders and finally general visceral pain. They found positive effects on pain and/or symptom relief, opioid consumption, anxiety and depression and QoL. Complications occurred frequently but were often minor and reversible.
UNASSIGNED: Better screening and selection criteria need to be established to optimally evaluate eligible patients who might benefit from SCS. A positive outcome of a sympathetic nerve block appears to be a potential indicator of SCS effectiveness. Additionally, women receiving SCS for endometriosis had a better outcome compared to other indications. Finally, SCS could also relief functional symptoms such as voiding problems and gastroparesis. Complications could often be resolved with revision surgery. Since SCS is expensive and not always covered by standard health insurance, the incorporation of cost-analyses is recommended. In order to establish a comprehensive treatment plan, including selection criteria for SCS, rigorous prospective, possibly randomized and controlled studies that are diagnosis-oriented, with substantial follow-up and adequate sample sizes, are needed.

OBJECTIVE: Chronic abdominal wall pain is a poorly recognized cause of chronic abdominal pain, and patients frequently go misdiagnosed despite a battery of medical tests. The Carnett\'s test is a diagnostic tool used to distinguish between abdominal wall pain and visceral pain. This review synthesizes the current literature on the Carnett\'s test, merges the viewpoints of diverse writers, and evaluates and reports on the Carnett\'s test\'s applicability.
RESULTS: Several clinical investigations have established the usefulness of the Carnett\'s test in the diagnosis of chronic abdominal wall pain. Furthermore, the Carnett\'s test is quite useful in determining the depth of the mass and detecting psychogenic abdominal pain. However, its diagnostic use for acute abdominal pain is limited. The Carnett\'s test is a simple and safe point-of-care diagnostic technique, with several studies supporting its usefulness. Early detection of abdominal wall pain is critical for chronic abdominal wall pain therapy. Carnett\'s test is very useful in patients with chronic, unexplained local abdominal discomfort who are compliant and do not have a clear rationale for surgery.

BACKGROUND: Visceral hypersensitivity (VH) is an overreaction of the gastrointestinal (GI) tract to various stimuli and is characterized by hyperalgesia and/or allodynia. VH contributes to the etiology of many GI dysfunctions, particularly irritable bowel syndrome (IBS). Although the exact mechanisms underlying VH are yet to be found, inflammation and oxidative stress, psychosocial factors, and sensorimotor alterations may play significant roles in it.
OBJECTIVE: In this review, we provide an overview of VH and its pathophysiological function in GI disorders. Adverse effects of synthetic drugs may make herbal agents a good candidate for pain management. Therefore, in this review, we will discuss the efficacy of herbal agents in the management of VH with a focus on their anti-inflammatory and antioxidant potentials.
METHODS: Data were extracted from clinical and animal studies published in English between 2004 and June, 2020, which were collected from PubMed, Google Scholar, Scopus, and Cochrane Library.
RESULTS: Overall, Radix, Melissia, Glycyrrhizae, Mentha, and Liquorice were the most efficient herbals for VH management in IBS and dyspepsia, predominantly through modulation of the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and suppression of 5- hydroxytryptamine 3 (5-HT3) or the serotonin receptors.
CONCLUSIONS: Considering the positive effects of herbal formulations in VH management, further research on novel herbal and/or herbal/chemical preparations is warranted.

While visceral pain is commonly associated with disorders of the gut-brain axis, underlying mechanisms are not fully understood. Dorsal root ganglion (DRG) neurons innervate visceral structures and undergo hypersensitization in inflammatory models. The characterization of peripheral DRG neuron terminals is an active area of research, but recent work suggests that they communicate with enteroendocrine cells (EECs) in the gut. EECs sense stimuli in the intestinal lumen and communicate information to the brain through hormonal and electrical signaling. In that context, EECs are a target for developing therapeutics to treat visceral pain. Linaclotide is an FDA-approved treatment for chronic constipation that activates the intestinal membrane receptor guanylyl cyclase C (GUCY2C). Clinical trials revealed that linaclotide relieves both constipation and visceral pain. We recently demonstrated that the analgesic effect of linaclotide reflects the overexpression of GUCY2C on neuropod cells, a specialized subtype of EECs. While this brings some clarity to the relationship between linaclotide and visceral analgesia, questions remain about the intracellular signaling mechanisms and neurotransmitters mediating this communication. In this Fundamental Neurochemistry Review, we discuss what is currently known about visceral nociceptors, enteroendocrine cells, and the gut-brain axis, and ongoing areas of research regarding that axis and visceral pain.

Visceral pain is a complex and heterogeneous pain condition that is often associated with pain-related negative emotional states, including anxiety and depression, and can exert serious effects on a patient\'s physical and mental health. According to modeling stimulation protocols, the current animal models of visceral pain mainly include the mechanical dilatation model, the ischemic model, and the inflammatory model. Acupuncture can exert analgesic effects by integrating and interacting input signals from acupuncture points and the sites of pain in the central nervous system. The brain nuclei involved in regulating visceral pain mainly include the nucleus of the solitary tract, parabrachial nucleus (PBN), locus coeruleus (LC), rostral ventromedial medulla (RVM), anterior cingulate cortex (ACC), paraventricular nucleus (PVN), and the amygdala. The neural circuits involved are PBN-amygdala, LC-RVM, amygdala-insula, ACC-amygdala, claustrum-ACC, bed nucleus of the stria terminalis-PVN and the PVN-ventral lateral septum circuit. Signals generated by acupuncture can modulate the central structures and interconnected neural circuits of multiple brain regions, including the medulla oblongata, cerebral cortex, thalamus, and hypothalamus. This analgesic process also involves the participation of various neurotransmitters and/or receptors, such as 5-hydroxytryptamine, glutamate, and enkephalin. In addition, acupuncture can regulate visceral pain by influencing functional connections between different brain regions and regulating glucose metabolism. However, there are still some limitations in the research efforts focusing on the specific brain mechanisms associated with the effects of acupuncture on the alleviation of visceral pain. Further animal experiments and clinical studies are now needed to improve our understanding of this area.

Patients with inflammatory bowel disease often experience ongoing pain even after achieving mucosal healing (i.e., post-inflammatory pain). Factors related to the brain-gut axis, such as peripheral and central sensitization, altered sympatho-vagal balance, hypothalamic-pituitary-adrenal axis activation, and psychosocial factors, play a significant role in the development of post-inflammatory pain. A comprehensive study investigating the interaction between multiple predisposing factors, including clinical psycho-physiological phenotypes, molecular mechanisms, and multi-omics data, is still needed to fully understand the complex mechanism of post-inflammatory pain. Furthermore, current treatment options are limited and new treatments consistent with the underlying pathophysiology are needed to improve clinical outcomes.

Different gentian preparations are used as traditional remedies for internal pain control in: Persian traditional medicine (PTM), Chinese traditional medicine (CTM) and Ancient Greek medicine (AGM) from the time of the Roman Empire. Objective: To present a survey of the ethnopharmacological applications of gentians recorded as being used in Eastern and Western traditional medical systems (PTM, CTM and AGM) and their pharmacological effects, chemical composition as well as an in silico investigation of the possible active component/s for the alleviation of internal pain via molecular docking studies. Major traditional medicine literature (PTM, CTM and AGM, 50 AD- 1770) and ethnobotanical studies for the application of gentians were reviewed. Nine European species representing 5 of the 13 sections currently attributed to Gentiana were selected. Chemical compounds and pharmacological activity data of these species were gathered from different databases including Google Scholar, PubChem, PubMed and Web of Science (between 1972 and 2020). The possible active constituents of gentians on visceral pain receptors were investigated, in silico. In all investigated literature, traditional uses of gentian were indicated to have anti-nociceptive effects on visceral pain and possess diuretic action. According to our computational study, acylated flavonoid glycosides, viz. trans-feruloyl-2\"-isovitexin (33), trans-feruloyl-2\"-isovitexin-4\'-O-β-D-glucoside (34), iso-orientin-4\'-O-glucoside (38), trans-caffeoyl-2\"-iso-orientin-4\'-O-β-D-glucoside (39), iso-orientin-2\"-O-β-D-glucoside (40) and isoscoparin (41), might be responsible for visceral pain reduction by interacting with the purinergic receptor (P2X3) and vanilloid receptor 1 (TrpV1). This finding shows a good correlation with different traditional gentian uses in Persian, Chinese and European ethnomedicine for visceral pain control.

The purpose of this narrative review was to show that referred orofacial pain can be the chief symptom or a prominent symptom of visceral diseases of the chest and throat, with implications for dental and medical practice.
A search of PubMed was performed to identify dentally relevant clinical case reports and case series using the following terms: jaw pain, orofacial pain, toothache, temporomandibular disorders, otalgia, neuralgia, and neuropathicpain crossed with angina, myocardial infarction, carotid artery, esophagus, mediastinum, thyroid, heart, pericardium, aorta, lung, thymus gland, and stomach.
Numerous acute, visceral disorders of the throat and chest have been reported to produce pain in the orofacial region, which may be difficult to distinguish from dental-related diseases on the basis of symptoms alone. Chest organs and structures reported to cause such pain include the heart, aorta, esophagus, stomach, lungs, and mediastinum. Throat organs and structures reported to cause pain in the orofacial region include the thyroid gland, carotid arteries, and vagus and glossopharyngeal nerves. Coronary artery diseases, aortic and carotid dissection, mediastinal tumors, subacute thyroiditis, and gastroesophageal reflux disease have a predilection for referring pain orofacially.
Misdiagnosis of referred visceral orofacial pain can lead to delayed diagnosis and unnecessary treatment. Dentists can play a key role in the management of these conditions by means of ruling out odontogenic facial pain, promptly referring patients to medical specialists, and educating patients. Future research is needed to determine the incidence and mechanism of orofacial pain in these disorders. Visceral pain referred to the orofacial region may not be as rare a phenomenon as is sometimes assumed.

BACKGROUND: Irritable bowel syndrome (IBS) is a highly prevalent and economically burdensome condition; and pain is often the most unpleasant, disruptive, and difficult-to-treat symptom. Visceral hypersensitivity is a common feature driving pain in IBS, suggesting that neuropathic mechanisms may be implicated. We conducted a systematic review of available evidence to examine the role of anti-neuropathic medicines in the management of pain in IBS.
METHODS: We systematically searched scientific repositories for trials investigating conventional oral, and/or parenteral, pharmaceutical antineuropathic treatments in patients with IBS. We summarized key participant characteristics, outcomes related to pain (primary outcome), and selected secondary outcomes.
RESULTS: We included 13 studies (n = 629 participants): six investigated amitriptyline, three duloxetine, three pregabalin, and one gabapentin. There was considerable methodological and statistical heterogeneity, so we performed a narrative synthesis and limited meta-analysis. Amitriptyline was most extensively studied, though only in diarrhea-predominant patients. In individual trials, amitriptyline, pregabalin and gabapentin generally appeared beneficial for pain outcomes. While duloxetine studies tended to report improvements in pain, all were un-controlled trials with high risk of bias. Meta-analysis of three studies (n = 278) yielded a pooled relative-risk of 0.50 (95%CI 0.38-0.66) for not improving with anti-neuropathic agent vs control. We did not identify any eligible studies investigating the role of parenteral anti-neuropathics.
UNASSIGNED: Anti-neuropathic analgesics may improve pain in IBS, and deserve further, high-quality investigation, potentially considering parenteral administration and agents with minimal gastrointestinal motility effects. Investigation of amitriptyline\'s efficacy in non-diarrhea-predominant subtypes is currently lacking, and we recommend particular caution for its use in IBS-C.

OBJECTIVE: Pain is a prevalent symptom in the lives of patients with cancer. In light of the ongoing opioid epidemic and increasing awareness of the potential for opioid abuse and addiction, clinicians are progressively turning to interventional therapies. This article reviews the interventional techniques available to mitigate the debilitating effects that untreated or poorly treated pain have in this population.
RESULTS: A range of interventional therapies and technical approaches are available for the treatment of cancer-related pain. Many of the techniques described may offer effective analgesia with less systemic toxicity and dependency than first- and second-line oral and parenteral agents. Neuromodulatory techniques including dorsal root ganglion stimulation and peripheral nerve stimulation are increasingly finding roles in the management of oncologic pain. The goal of this pragmatic narrative review is to discuss interventional approaches to cancer-related pain and the potential of such therapies to improve the quality of life of cancer patients.