Neural circuits regulating visceral pain.

Visceral hypersensitivity, a common clinical manifestation of irritable bowel syndrome, may contribute to the development of chronic visceral pain, which is a major challenge for both patients and health providers. Neural circuits in the brain encode, store, and transfer pain information across brain regions. In this review, we focus on the anterior cingulate cortex and paraventricular nucleus of the hypothalamus to highlight the progress in identifying the neural circuits involved in visceral pain. We also discuss several neural circuit mechanisms and emphasize the importance of cross-species, multiangle approaches and the identification of specific neurons in determining the neural circuits that control visceral pain.

Effect of deep neuromuscular block on the quality of early recovery after sleeve gastrectomy in obese patients: a randomized controlled trial.

BACKGROUND: Deep neuromuscular block (NMB) has been shown to improve surgical conditions and alleviate post-operative pain in bariatric surgery compared with moderate NMB. We hypothesized that deep NMB could also improve the quality of early recovery after laparoscopic sleeve gastrectomy (LSG). METHODS: Eighty patients were randomized to receive either deep (post-tetanic count 1-3) or moderate (train-of-four count 1-3) NMB. The QoR-15 questionnaire was used to evaluate the quality of early recovery at 1 day before surgery (T0), 24 and 48 h after surgery (T2, T3). Additionally, we recorded diaphragm excursion (DE), postoperative pain, surgical condition, cumulative dose of analgesics, time of first flatus and ambulation, post-operative nausea and vomiting, time of tracheal tube removal and hospitalization time. MAIN RESULTS: The quality of recovery was significantly better 24 h after surgery in patients who received a deep versus moderate block (114.4 ± 12.9 versus 102.1 ± 18.1). Diaphragm excursion was significantly greater in the deep NMB group when patients performed maximal inspiration at T2 and T3 (P < 0.05). Patients who underwent deep NMB reported lower visceral pain scores 40 min after surgery; additionally, these patients experienced lower pain during movement at T3 (P < 0.05). Optimal surgical conditions were rated in 87.5% and 64.6% of all measurements during deep and moderate NMB respectively (P < 0.001). The time to tracheal tube removal was significantly longer in the deep NMB group (P = 0.001). There were no differences in other outcomes. CONCLUSION: In obese patients receiving deep NMB during LSG, we observed improved QoR-15 scores, greater diaphragmatic excursions, improved surgical conditions, and visceral pain scores were lower. More evidence is needed to determine the effects of deep NMB on these outcomes. TRIAL REGISTRATION: ChiCTR2200065919. Date of retrospectively registered: 18/11/2022.

Effectiveness of Butorphanol in alleviating intra- and post-operative visceral pain following microwave ablation for hepatic tumor: a dual-central, randomized, controlled trial.

Many patients who underwent hepatic percutaneous microwave ablation (MWA) reported experiencing pain during the procedure. This study utilized a well-designed multicentral, randomized, and placebo-controlled format to investigate the effects of Butorphanol. Patients who underwent MWA were randomly assigned to either Butorphanol or normal saline group. The primary outcomes of the study were assessed by measuring the patients' intraoperative pain levels using a 10-point visual analog scale (VAS). Secondary outcomes included measuring postoperative pain levels at the 6-h mark (VAS) and evaluating comprehensive pain assessment outcomes. A total of 300 patients were divided between the control group (n = 100) and the experimental group (n = 200). Butorphanol showed statistically significant reductions in intraoperative pain levels compared to the placebo during surgery (5.00 ± 1.46 vs. 3.54 ± 1.67, P < 0.001). Significant differences were observed in postoperative pain levels at the 6-h mark and in the overall assessment of pain (1.39 + 1.21 vs. 0.65 + 0.81, P < 0.001). Butorphanol had a significant impact on reducing the heart rate of patients. The empirical evidence supports the effectiveness of Butorphanol in reducing the occurrence of visceral postoperative pain in patients undergoing microwave ablation for hepatic tumor. Furthermore, the study found no noticeable impact on circulatory and respiratory dynamics.

Overexpression of EphB2 in the basolateral amygdala is crucial for inducing visceral pain sensitization in rats subjected to water avoidance stress.

AIMS: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process. METHODS: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety- and depression-like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot. RESULTS: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety-like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety-like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N-methyl-D-aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety-like behaviors. CONCLUSIONS: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS-like symptoms. These findings may give insight into the treatment of IBS and related psychological distress.

Intracerebroventricular administration of TRH Agonist, RX-77368 alleviates visceral pain induced by colorectal distension in rats.

Thyrotropin-releasing hormone (TRH) acts centrally to exert pleiotropic actions independently from its endocrine function, including antinociceptive effects against somatic pain in rodents. Whether exogenous or endogenous activation of TRH signaling in the brain modulates visceral pain is unknown. Adult male Sprague-Dawley rats received an intracerebroventricular (ICV) injection of the stable TRH analog, RX-77368 (10, 30 and 100 ng/rat) or saline (5 µl) or were semi-restrained and exposed to cold (4°C) for 45 min. The visceromotor response (VMR) to graded phasic colorectal distensions (CRD) was monitored using non-invasive intracolonic pressure manometry. Naloxone (1 mg/kg) was injected subcutaneously 10 min before ICV RX-77368 or saline. Fecal pellet output was monitored for 1 h after ICV injection. RX-77368 ICV (10, 30 and 100 ng/rat) reduced significantly the VMR by 56.7%, 67.1% and 81.1% at 40 mmHg and by 30.3%, 58.9% and 87.4% at 60 mmHg respectively vs ICV saline. Naloxone reduced RX-77368 (30 and 100 ng, ICV) analgesic response by 51% and 28% at 40 mmHg and by 30% and 33% at 60 mmHg respectively, but had no effect per se. The visceral analgesia was mimicked by the acute exposure to cold. At the doses of 30 and 100 ng, ICV RX-77368 induced defecation within 30 min. These data established the antinociceptive action of RX-77368 injected ICV in a model of visceral pain induced by colonic distension through recruitment of both opioid and non-opioid dependent mechanisms.

Menthacarin treatment attenuates nociception in models of visceral hypersensitivity.

BACKGROUND: Chronic visceral hypersensitivity is closely associated with irritable bowel syndrome (IBS), a very common disorder which significantly impairs quality of life, characterized by abdominal pain, and distension. Imaging studies have found that IBS patients show higher metabolic activities and functional differences from normal controls in the anterior cingulate cortex (ACC), in response to visceral pain stimulation. Non-clinical data and clinical data suggest that medicinal products containing essential oils such as peppermint or caraway oil exert beneficial effects on IBS symptoms. METHODS: We assessed acute and long-term treatment effects of a mixture of peppermint and caraway essential oils (Menthacarin) on brain electrophysiological markers of gut pain sensitivity in two rat models of visceral hypersensitivity. KEY RESULTS: Chronic administration of corticosteroids and acute repeated mechanical hyperstimulation under anesthesia induced hyperalgesia and hypersensitivity, characterized by an increase in electrophysiological excitatory responses of ACC neurons to colorectal distension (CRD) and an increase in the proportion of neurons responding to otherwise subthreshold stimulation, respectively. Long-term, but not acute, oral administration of Menthacarin (60 mg kg-1 day-1) significantly reduced the net excitatory response to CRD in normally responsive control animals and counteracted the development of visceral hyperalgesia and hypersensitivity induced by repeated corticosterone administration and acute mechanical stimulation. CONCLUSIONS & INFERENCES: The present study shows that, using the CRD method, chronic Menthacarin administration at a clinically relevant dose attenuates the neuronal discharge associated with visceral pain stimuli in the rat ACC, particularly in models of hypersensitivity, suggesting a potential for treating exaggerated visceral pain sensitivity.

The Diagnostic Value of Carnett's Test with Chronic Abdominal Pain: A Narrative Review.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.

The Gut Microbiota and Chronic Pain.

PURPOSE OF REVIEW: To examine the effects and interactions between gut microbia and chronic pain. RECENT FINDINGS: The gut microbiome has been an area of interest in both the scientific and general audience due to a growing body of evidence suggesting its influence in a variety of health and disease states. Communication between the central nervous system (CNS) and gut microbiome is said to be bidirectional, in what is referred to as the gut-brain axis. Chronic pain is a prevalent costly personal and public health burden and so, there is a vested interest in devising safe and efficacious treatments. Numerous studies, many of which are animal studies, have been conducted to examine the gut microbiome's role in the pathophysiology of chronic pain states, such as neuropathy, inflammation, visceral pain, etc. As the understanding of this relationship grows, so does the potential for therapeutic targeting of the gut microbiome in chronic pain.

Purine nucleoside phosphorylase inhibition is an effective approach for the treatment of chemical hemorrhagic cystitis.

Hemorrhagic cystitis may be induced by infection, radiation therapy, or medications or may be idiopathic. Along with hemorrhagic features, symptoms include urinary urgency and frequency, dysuria (painful urination), and visceral pain. Cystitis-induced visceral pain is one of the most challenging types of pain to treat, and an effective treatment would address a major unmet medical need. We assessed the efficacy of a purine nucleoside phosphorylase inhibitor, 8-aminoguanine (8-AG), for the treatment of hemorrhagic/ulcerative cystitis. Lower urinary tract (LUT) function and structure were assessed in adult Sprague-Dawley rats, treated chronically with cyclophosphamide (CYP; sacrificed day 8) and randomized to daily oral treatment with 8-AG (begun 14 days prior to CYP induction) or its vehicle. CYP-treated rats exhibited multiple abnormalities, including increased urinary frequency and neural mechanosensitivity, reduced bladder levels of inosine, urothelial inflammation/damage, and activation of spinal cord microglia, which is associated with pain hypersensitivity. 8-AG treatment of CYP-treated rats normalized all observed histological, structural, biochemical, and physiological abnormalities. In cystitis 8-AG improved function and reduced both pain and inflammation likely by increasing inosine, a tissue-protective purine metabolite. These findings demonstrate that 8-AG has translational potential for reducing pain and preventing bladder damage in cystitis-associated LUT dysfunctions.

Mucosal neuroimmune mechanisms in gastro-oesophageal reflux disease (GORD) pathogenesis.

Gastro-oesophageal reflux disease (GORD) is a chronic condition characterised by visceral pain in the distal oesophagus. The current first-line treatment for GORD is proton pump inhibitors (PPIs), however, PPIs are ineffective in a large cohort of patients and long-term use may have adverse effects. Emerging evidence suggests that nerve fibre number and location are likely to play interrelated roles in nociception in the oesophagus of GORD patients. Simultaneously, alterations in cells of the oesophageal mucosa, namely epithelial cells, mast cells, dendritic cells, and T lymphocytes, have been a focus of GORD research for several years. The oesophagus of GORD patients exhibits both macro- and micro-inflammation as a response to chronic acidic reflux at the epithelium. In other conditions of the GI tract, such as IBS and IBD, well-characterised bidirectional processes between immune cells and mucosal nerve fibres contribute to pathogenesis and symptom generation. Sensory alterations in these conditions such as nerve fibre outgrowth and hypersensitivity can be driven by inflammatory processes, which promote visceral pain signalling. This review will examine what is currently known of the molecular pathways linking inflammation and sensory perception leading to the development of GORD symptoms and explore potentially relevant mechanisms in other GI regions which may indicate new areas in GORD research.

Early in life stressful events induce chronic visceral pain and changes in bladder function in adult female mice through a mechanism involving TRPV1 and alpha 1A adrenoceptors.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder with multiple phenotypes, one of which is associated with an overactive adrenergic system. OBJECTIVE: We investigated if the maternal deprivation model (MDM) in female and male mice mimics IC/BPS phenotype and if the overstimulation of alpha 1A adrenoceptor (A1AAR) and the crosstalk with transient receptor potential vanilloid-1 (TRPV1) are involved in the generation of pain and bladder functional changes. DESIGN, SETTING, AND PARTICIPANTS: C57BL/6 female and male mice were submitted to MDM. TRPV1 knockout (KO) mice were used to study TRPV1 involvement. Silodosin administration to MDM mice was used to study A1AAR involvement. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was chronic visceral pain measured by Von Frey filaments analysis (effect size: 3 for wild type, 3.9 for TRPV1 KO). Bladder changes were secondary outcome measurements. Unpaired T test, Mann-Whitney test, one-way analysis of variance followed by Newman-Keuls multiple comparisons test, and Kruskal-Wallis followed by Dunn's multiple comparisons test were used where appropriate. RESULTS AND LIMITATIONS: MDM induces pain behavior in female and not in male mice. Bladder afferents seem sensitize as MDM also increase the number of small volume spots voided, the bladder reflex activity, and urothelial damage. These changes were similarly absent after A1AAR blockade with silodosin or by TRPV1 gene KO. The main limitation is the number/type of pain tests used. CONCLUSIONS: MDM induced in female mice is able to mimic IC/BPS phenotype, through mechanisms involving A1AAR and TRPV1. Therefore, the modulation of both receptors may represent a therapeutic approach to treat IC/BPS patients.

Sex differences in zymosan-induced behavioral visceral hypersensitivity and colorectal afferent sensitization.

Sex differences in visceral nociception have been reported in clinical and preclinical studies, but the potential differences in sensory neural encoding of the colorectum between males and females are not well understood. In this study, we systematically assessed sex differences in colorectal neural encoding by conducting high-throughput optical recordings in intact dorsal root ganglia (DRGs) from control and visceral hypersensitive mice. We found an apparent sex difference in zymosan-induced behavioral visceral hypersensitivity: enhanced visceromotor responses to colorectal distension were observed only in male mice, not in female mice. In addition, a higher number of mechanosensitive colorectal afferents were identified per mouse in the zymosan-treated male group than in the saline-treated male group, whereas the mechanosensitive afferents identified per mouse were comparable between the zymosan- and saline-treated female groups. The increased number of identified afferents in zymosan-treated male mice was predominantly from thoracolumbar (TL) innervation, which agrees with the significant increase in the TL afferent proportion in the zymosan group as compared with the control group in male mice. In contrast, female mice showed no difference in the proportion of colorectal neurons between saline- and zymosan-treated groups. Our results revealed a significant sex difference in colorectal afferent innervation and sensitization in the context of behavioral visceral hypersensitivity, which could drive differential clinical symptoms in male and female patients.NEW & NOTEWORTHY We used high-throughput GCaMP6f recordings to study 2,275 mechanosensitive colorectal afferents in mice. Our results revealed significant sex differences in the zymosan-induced behavioral visceral hypersensitivity, which were present in male but not female mice. Male mice also showed sensitization of colorectal afferents in the thoracolumbar pathway, whereas female mice did not. These findings highlight sex differences in sensory neural anatomy and function of the colorectum, with implications for sex-specific therapies for treating visceral pain.

Non-Intoxicating Cannabinoids in Visceral Pain.

Cannabis and cannabis products are becoming increasingly popular options for symptom management of inflammatory bowel diseases, particularly abdominal pain. While anecdotal and patient reports suggest efficacy of these compounds for these conditions, clinical research has shown mixed results. To date, clinical research has focused primarily on delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is a ligand of classical cannabinoid receptors (CBRs). CBD is one of a large group of nonintoxicating cannabinoids (niCBs) that mediate their effects on both CBRs and through non-CBR mechanisms of action. Because they are not psychotropic, there is increasing interest and availability of niCBs. The numerous niCBs show potential to rectify abnormal intestinal motility as well as have anti-inflammatory and analgesic effects. The effects of niCBs are frequently not mediated by CBRs, but rather through actions on other targets, including transient receptor potential channels and voltage-gated ion channels. Additionally, evidence suggests that niCBs can be combined to increase their potency through what is termed the entourage effect. This review examines the pre-clinical data available surrounding these niCBs in treatment of abdominal pain with a focus on non-CBR mechanisms.

Sex differences in visceral sensitivity and brain activity in a rat model of comorbid pain: a longitudinal study.

ABSTRACT: Temporomandibular disorder (TMD) and irritable bowel syndrome (IBS) are 2 chronic overlapping pain conditions (COPCs) that present with significant comorbidity. Both conditions are more prevalent in women and are exacerbated by stress. While peripheral mechanisms might contribute to pain hypersensitivity for each individual condition, mechanisms underlying the comorbidity are poorly understood, complicating pain management when multiple conditions are involved. In this study, longitudinal behavioral and functional MRI-based brain changes have been identified in an animal model of TMD-like pain (masseter muscle inflammation followed by stress) that induces de novo IBS-like comorbid visceral pain hypersensitivity in rats. In particular, data indicate that increased activity in the insula and regions of the reward and limbic systems are associated with more pronounced and longer-lasting visceral pain behaviors in female rats, while the faster pain resolution in male rats may be due to increased activity in descending pain inhibitory pathways. These findings suggest the critical role of brain mechanisms in chronic pain conditions and that sex may be a risk factor of developing COPCs.

Vicarious facilitation of facial responses to pain.

INTRODUCTION: Observing facial expressions of pain has been shown to lead to increased subjective, neural and autonomic pain responses. Surprisingly, these vicarious facilitation effects on its corresponding response channel, namely facial responses to pain have mostly been neglected. We aim to examine whether the prior exposure to facial expressions of pain leads to a facilitation of facial responses to experimental pain; and whether this facilitation is linked to the valence (pain vs. neutral expression) or also linked to specific motor-features of the facial pain expressions (different facial muscle movements). METHOD: Subjective (intensity and unpleasantness ratings) and facial responses (Facial Action Coding System) of 64 participants (34 female) to painful and non-painful heat stimuli were assessed. Before each heat stimulus, video clips of computer-generated facial expressions (three different pain expressions and a neutral expression) were presented. RESULTS: The prior exposure to facial expressions of pain led to increased subjective and facial responses to pain. Further, vicarious pain facilitation of facial responses was significantly correlated with facilitation of unpleasantness ratings. We also found evidence that this vicarious facilitation of facial responses was not only linked to the presentation of pain versus neutral expressions but also to specific motor-features of the pain cue (increase in congruent facial muscle movements). DISCUSSION: Vicarious pain facilitation was found for subjective and facial responses to pain. The results are discussed with reference to the motivational priming hypothesis as well as with reference to motor priming. SIGNIFICANCE: Our study uncovers evidence that facial pain responses are not only influenced by motivational priming (similar to other types of pain responses), but also by motor-priming. These findings shed light on the complexity - ranging from social, affective and motor mechanisms - underling vicarious facilitation of pain.

Fundamental Neurochemistry Review: The role of enteroendocrine cells in visceral pain.

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.

Peripheral neural mechanism of visceral pain and acupoint sensitization in 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis model mice. / ç»“è‚ ç‚Žæ¨¡åž‹å°é¼ å† è„ç—›åŠç©´ä½æ•åŒ–çš„å¤–å‘¨ç¥žç»æœºåˆ¶æŽ¢è®¨.

OBJECTIVES: To explore the neural mechanism of visceral pain and related somatic (acupoints) sensitization by using in vivo calcium imaging of dorsal root ganglia (DRG) neurons. METHODS: Eight BALB/c mice were randomly divided into control and model groups, with 4 mice in each group. The colitis model was induced by colorectal perfusion of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) once daily for 7 days. Mice of the control group received colorectal perfusion of normal saline once daily for 7 days. The location and area of the somatic neurogenic inflammation (cutaneous exudation of Evans blue ï¼»EBï¼½) of the 2 groups of mice were observed after intravenous injection of EB. For pain behavioral tests, sixteen C57BL/6J mice were randomly divided into control and model groups, with 8 mice in each group, and a Von Frey filament was used to stimulate the referred somatic reactive regions in colitis mice, and the number of avoidance and paw withdraw reaction within 10 tests was recorded. For in vivo DRG calcium imaging tests, 24 Pirt-GCaMP6s transgenic mice were randomly and equally divided into control group and colitis model group. The responses of the neurons in L6 or L4 DRG to colorectal distension (CRD), lower back brushing, or mechanical stimulation at the hindpaw were observed using confocal fluorescence microscope. RESULTS: Compared with the control group, the area of EB exudation spot in the hindpaw and lower back regions was increased in the colitis model group (P<0.05), and the avoidance or paw withdraw numbers induced by Von Frey stimulation at the lower back and hindpaw were increased (P<0.01, P<0.05), indicating that colitis induced regional skin (acupoints) sensitization in the lower back and hindpaw regions. Compared with the control group, the percentage of L6 DRG neurons activated by 60 mm Hg CRD in the colitis model mice were apparently increased (P<0.01), the activated neurons mainly involved the medium-sized DRG neurons (P<0.01). In Pirt-GCaMP6s transgenic mice, following brushing the skin of the receptive field (lower back) of L6 DRG neurons, the fluorescence intensity of the brushing-activated DRG neurons and small, medium and large-sized neurons were significantly higher in the colitis model group than those in the control group (P<0.001, P<0.01, P<0.05). After brushing and clamping the skin of the right hindpaw (receptive field of L4 DRG neurons), the percentages of the activated L4 DRG neurons were obviously higher in the colitis model group than those in the control group (P<0.01, P<0.05), while there were no significant changes in the proportion of small, medium and large-sized neurons between the control and colitis model groups. CONCLUSIONS: Colitis may lead to body surface sensitization at the same and adjacent neuro-segments as well as to an increase of the number and activity of the responsive lumbar DRG neurons, among which the L6 DRG neurons at the same neuro-segment as the rectum colon showed an increase in the number of responders and intensity of calcium fluorescence signal while L4 DRG neurons at the level adjacent to the rectum colon showed an increase in the number of responders, suggesting that there may be different mechanisms of peripheral neural sensitization.

Clinical analysis of acute postoperative pain after total laparoscopic hysterectomy for adenomyosis and uterine fibroids - a prospective observational study.

OBJECTIVE: To investigate the outcome of total laparoscopic hysterectomy (TLH) and postoperative pain characteristics and compare the pain severity after TLH for adenomyosis or uterine fibroids. METHODS: This prospective observational study collected 101 patients received TLH for adenomyosis (AD group) including 41 patients were injected goserelin (3.6 mg) 28 days before TLH, while other adenomyosis patients received TLH without preoperative treatment, and 113 patients received TLH for uterine fibroids (UF group). Pain scores were evaluated at different time sites from operation day to postoperative 72 h using the numeric rating scale. Clinical data were collected from clinical record. RESULTS: Operative time and anaesthetic time were longer in the AD group than those in the UF group (66.88 ± 8.65 vs. 64.46 ± 7.21, p = 0.04; 83.95 ± 10.05 vs. 79.77 ± 6.88, p < 0.01), severe endometriosis was quite more common in AD group (23.76% vs. 2.65%, p < 0.01). Postoperative usage of Flurbiprofen in AD group were more than that of UF group (15.48 ± 38.00 vs. 4.79 ± 18.16, p = 0.02). Total pains and abdominal visceral pains of AD group were more severe compared with UF group in motion and rest pattern at several time sites, while incision pain and shoulder pain were similar. The total postoperative pains after goserelin preoperative treatment in AD group were less than that without goserelin preoperative treatment (p < 0.05). The levels of serum NPY, PGE2 and NGF after laparoscopic hysterectomy of adenomyosis reduced with GnRH agonist pretreatment. CONCLUSIONS: Acute postoperative pain for adenomyosis and uterine fibroids showed considerably different severity, postoperative total pain and abdominal visceral pains of TLH for adenomyosis were more severe compared with uterine fibroids. While patients received goserelin before laparoscopic hysterectomy of adenomyosis suffered from less severity of postoperative total pain than that without goserelin preoperative treatment.

Acute postoperative pain for adenomyosis and uterine fibroids showed considerably different severity, postoperative total pain and abdominal visceral pains of TLH for adenomyosis were more severe compared with uterine fibroids.Patients received goserelin before laparoscopic hysterectomy of adenomyosis suffered from less severity of postoperative total pain than that without goserelin preoperative treatment.

Spinal cord stimulation for visceral pain associated with medullary sponge kidney.

Chronic pain is a common reason for which people in the USA seek medical care. It is linked to opioid consumption, anxiety and a reduction in quality of life. Over the past 50 years, spinal cord stimulation (SCS) has evolved as a safe and efficacious treatment for chronic pain etiologies. The authors present the first known case of SCS for pain due to medullary sponge kidney disease. This report adds to the growing body of literature supporting the use of SCS for treating visceral organ pain, while also highlighting the utility of ventral lead placement for treating visceral pain. As SCS utilization increases, it is expected that there will be a decrease in opioid consumption, and this will help us contain the opioid epidemic.

Chronic pain is one of the most common reasons that people in the USA seek medical care. It is associated with an increased reliance on opioids, anxiety, depression and a lower quality of life. Over the past 50 years, a treatment modality known as spinal cord stimulation (SCS) has emerged and evolved. Based on evidence, SCS has shown promising results in treating chronic pain related to different causes and has also led to an improvement in the quality of life in those suffering from pain. In this case report, the authors present a case of a patient with chronic pain due to recurrent kidney stones secondary to their hereditary kidney disease, and who responded well to treatment with SCS. The patient self-reported almost 80% pain relief after undergoing treatment with SCS as well as an improved quality of life, based on their ability to engage in their daily professional and leisurely activities without being so restricted by pain from their recurrent kidney stones. This case report adds to the growing body of literature that underscores the utility of SCS in treating a variety of pain mediated pathologies. As SCS continues to show promising results, we hope that SCS usage to target pain will increase, and this will lead to a decrease in opioid prescriptions and help curb the opioid epidemic.

Enteric glia promote visceral hypersensitivity during inflammation through intercellular signaling with gut nociceptors.

Inflammation in the intestines causes abdominal pain that is challenging to manage. The terminals of sensory neurons innervating the gut are surrounded by glia. Here, using a mouse model of acute colitis, we found that enteric glia contribute to visceral pain by secreting factors that sensitized sensory nerves innervating the gut in response to inflammation. Acute colitis induced a transient increase in the production of proinflammatory cytokines in the intestines of male and female mice. Of these, IL-1ß was produced in part by glia and augmented the opening of the intercellular communication hemichannel connexin-43 in glia, which made normally innocuous stimuli painful in female mice. Chemogenetic glial activation paired with calcium imaging in nerve terminals demonstrated that glia sensitized gut-innervating nociceptors only under inflammatory conditions. This inflammatory, glial-driven visceral hypersensitivity involved an increased abundance of the enzyme COX-2 in glia, resulting in greater production and release of prostaglandin E2 that activated EP4 receptors on sensory nerve terminals. Blocking EP4 receptors reduced nociceptor sensitivity in response to glial stimulation in tissue samples from colitis-model mice, and impairing glial connexin-43 reduced visceral hypersensitivity induced by IL-1ß in female mice. The findings suggest that therapies targeting enteric glial-neuron signaling might alleviate visceral pain caused by inflammatory disorders.