In Vivo Calcium Imaging Visualizes Incision-Induced Primary Afferent Sensitization and Its Amelioration by Capsaicin Pretreatment.

Previous studies have shown that infiltration of capsaicin into the surgical site can prevent incision-induced spontaneous pain like behaviors and heat hyperalgesia. In the present study, we aimed to monitor primary sensory neuron Ca2+ activity in the intact dorsal root ganglia (DRG) using Pirt-GCaMP3 male and female mice pretreated with capsaicin or vehicle before the plantar incision. Intraplantar injection of capsaicin (0.05%) significantly attenuated spontaneous pain, mechanical, and heat hypersensitivity after plantar incision. The Ca2+ response in in vivo DRG and in in situ spinal cord was significantly enhanced in the ipsilateral side compared with contralateral side or naive control. Primary sensory nerve fiber length was significantly decreased in the incision skin area in capsaicin-pretreated animals detected by immunohistochemistry and placental alkaline phosphatase (PLAP) staining. Thus, capsaicin pretreatment attenuates incisional pain by suppressing Ca2+ response because of degeneration of primary sensory nerve fibers in the skin.SIGNIFICANCE STATEMENT Postoperative surgery pain is a major health and economic problem worldwide with ∼235 million major surgical procedures annually. Approximately 50% of these patients report uncontrolled or poorly controlled postoperative pain. However, mechanistic studies of postoperative surgery pain in primary sensory neurons have been limited to in vitro models or small numbers of neurons. Using an innovative, distinctive, and interdisciplinary in vivo populational dorsal root ganglia (DRG) imaging (>1800 neurons/DRG) approach, we revealed increased DRG neuronal Ca2+ activity from postoperative pain mouse model. This indicates widespread DRG primary sensory neuron plasticity. Increased neuronal Ca2+ activity occurs among various sizes of neurons but mostly in small-diameter and medium-diameter nociceptors. Capsaicin pretreatment as a therapeutic option significantly attenuates Ca2+ activity and postoperative pain.

Identification of Individuals with Functional Dyspepsia With a Simple, Minimally Invasive Test: A Single Center Cohort Study of the Oral Capsaicin Test.

OBJECTIVES: The diagnosis of functional dyspepsia (FD) is challenging due to the lack of reliable biological markers to support the diagnosis. We assessed the relevance of a previously validated simple test for chemical hypersensitivity in the setting of a gastrointestinal outpatient department. METHODS: A total of 224 outpatients who were referred for evaluation of gastrointestinal symptoms in the absence of alarm symptoms swallowed a capsule containing 0.75 mg capsaicin. Severity of symptoms before and after capsule ingestion was assessed by a graded questionnaire and the difference in aggregate symptom scores (delta) was calculated. RESULTS: Sensitivity of the test was between 0.51-0.59, specificity was 0.84-0.89 and positive predictive value for the diagnosis of FD 70-71%. FD patients had significantly higher median delta symptom scores (10.0; 25% quartile: 3.0; 75% quartile: 16.0) as compared to inflammatory bowel disease (2.5; 1.0/8.5)(P=0.003), peptic ulcer disease (0.0; -1.5/4.5) (P<0.001), irritable bowel syndrome (3.0;0.5/8.5)(P=0.001), and patients classified with "other disease" (2.5;0.0/5.0)(P<0.001). Patients with gastroesophageal reflux disease had significantly lower symptom scores if FD was not concomitantly diagnosed (2.0; 0.0/6.0) than if FD was present (10.0; 4.0/15.0). CONCLUSIONS: Hypersensitivity for capsaicin discriminates functional dyspepsia from patients with other GI disorders. The capsaicin test is a simple and non invasive method to detect a large subgroup of functional dyspepsia with chemical hypersensitivity. These findings might open new diagnostic options in functional dyspepsia and possibly new therapeutic options by targeting the specific capsaicin receptor TRPV1.

Baby Shampoo to Relieve the Discomfort of Tear Gas and Pepper Spray Exposure: A Randomized Controlled Trial.

INTRODUCTION: Oleoresin capsicum (OC) or pepper spray, and tear gas (CS) are used by police and the military and produce severe discomfort. Some have proposed that washing with baby shampoo helps reduce this discomfort. METHODS: We conducted a prospective, randomized, controlled study to determine if baby shampoo is effective in reducing the severity and duration of these effects. Study subjects included volunteers undergoing OC or CS exposure as part of their police or military training. After standardized exposure to OC or CS all subjects were allowed to irrigate their eyes and skin ad lib with water. Those randomized to the intervention group were provided with baby shampoo for application to their head, neck, and face. Participants rated their subjective discomfort in two domains on a scale of 0-10 at 0, 3, 5, 10, and 15 minutes. We performed statistical analysis using a two-tailed Mann-Whitney Test. RESULTS: There were 58 participants. Of 40 subjects in the OC arm of the study, there were no significant differences in the ocular or respiratory discomfort at any of the time points between control (n=19) and intervention (n=21) groups. Of 18 subjects in the CS arm, there were no significant differences in the ocular or skin discomfort at any of the time points between control (n=8) and intervention (n=10) groups. CONCLUSION: Irrigation with water and baby shampoo provides no better relief from OC- or CS-induced discomfort than irrigation with water alone.

Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is characterized by symptoms of cyclic abdominal pain, nausea, and vomiting in the setting of prolonged cannabis use. The transient receptor potential vanilloid 1 (TRPV1) receptor may be involved in this syndrome. Topical capsaicin is a proposed treatment for CHS; it binds TRPV1 with high specificity, impairing substance P signaling in the area postrema and nucleus tractus solitarius via overstimulation of TRPV1. This may explain its apparent antiemetic effect in this syndrome. PURPOSE: We describe a series of thirteen cases of suspected cannabis hyperemesis syndrome treated with capsaicin in the emergency departments of two academic medical centers. METHODS: A query of the electronic health record at both centers identified thirteen patients with documented daily cannabis use and symptoms consistent with CHS who were administered topical capsaicin cream for symptom management. RESULTS: All 13 patients experienced symptom relief after administration of capsaicin cream. CONCLUSION: Topical capsaicin was associated with improvement in symptoms of CHS after other treatments failed.

Capsaicin Supplementation Reduces Physical Fatigue and Improves Exercise Performance in Mice.

Chili pepper is used as a food, seasoning and has been revered for its medicinal and health claims. It is very popular and is the most common spice worldwide. Capsaicin (CAP) is a major pungent and bioactive phytochemical in chili peppers. CAP has been shown to improve mitochondrial biogenesis and adenosine triphosphate (ATP) production. However, there is limited evidence around the effects of CAP on physical fatigue and exercise performance. The purpose of this study was to evaluate the potential beneficial effects of CAP on anti-fatigue and ergogenic functions following physiological challenge. Female Institute of Cancer Research (ICR) mice from four groups (n = 8 per group) were orally administered CAP for 4 weeks at 0, 205, 410, and 1025 mg/kg/day, which were respectively designated the vehicle, CAP-1X, CAP-2X, and CAP-5X groups. The anti-fatigue activity and exercise performance was evaluated using forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, BUN (blood urea nitrogen) and creatine kinase (CK) after a 15-min swimming exercise. The grip strength and exhaustive swimming time of the CAP-5X group were significantly higher than other groups. CAP supplementation dose-dependently reduced serum lactate, ammonia, BUN and CK levels, and increased glucose concentration after the 15-min swimming test. In addition, CAP also increased hepatic glycogen content, an important energy source for exercise. The possible mechanism was relevant to energy homeostasis and the physiological modulations by CAP supplementation. Therefore, our results suggest that CAP supplementation may have a wide spectrum of bioactivities for promoting health, performance improvement and fatigue amelioration.

Healthy Subjects Differentially Respond to Dietary Capsaicin Correlating with Specific Gut Enterotypes.

CONTEXT: Previous population studies in evaluating the beneficial effects of capsaicin (CAP) have yielded inconclusive results, and the mechanisms responsible for possible benefit remain unclear. OBJECTIVE: The objective was to assess the effect of dietary CAP on metabolic and immune profiles and its potential associations with gut microbial patterns in healthy adults. DESIGN: In a 6-week controlled feeding trial, subjects were given the weight maintenance diet sequentially contained with 0, 5, 0, and 10 mg/d CAP from chili powder. SETTING AND PARTICIPANTS: The study was conducted in 12 healthy subjects enrolled in Third Military Medical University in Chongqing. MAIN OUTCOME MEASURES: At the end of each period, anthropometric and basal metabolism measures together with blood and fecal samples were collected. Plasma metabolic and inflammatory markers and gut microbial ecology of each subject were subsequently assessed. RESULT: Dietary CAP increased the Firmicutes/Bacteroidetes ratio and Faecalibacterium abundance, accompanied with increased plasma levels of glucagon-like peptide 1 and gastric inhibitory polypeptide and decreased plasma ghrelin level. Further enterotype analysis revealed that these subjects could be clustered into Bacteroides enterotype (E1) and Prevotella enterotype (E2), and the above beneficial effects were mainly obtained in E1 subjects. Moreover, E1 subjects had significantly higher fecal Faecalibacterium abundance and butyrate concentration after CAP interventions than those in E2 subjects. CONCLUSION: Our study showed that gut enterotypes may influence the beneficial effects of dietary CAP, providing new evidence for the personalized nutrition guidance of CAP intervention on health promotion linking with gut microbiota patterns.

Amitriptyline, but Not Pregabalin, Reverses the Attenuation of Noxious Stimulus-Induced Analgesia After Nerve Injury in Rats.

BACKGROUND: Noxious stimulus-induced analgesia (NSIA) is a type of conditioned pain modulation in rats that has been used to assess endogenous pain control systems. The descending noradrenergic system is involved in NSIA, and nerve injury induces plastic changes of descending noradrenergic neurons. Thus, we hypothesized that nerve injury would affect NSIA strength and that amitriptyline and pregabalin, which often are used for treating neuropathic pain, might further modulate NSIA through effects on the descending noradrenergic system. METHODS: We examined the change in NSIA over time after right L5 spinal nerve ligation (SNL) in rats by measuring the contralateral hind paw withdrawal threshold after left forepaw capsaicin injection. In addition, we examined NSIA after 5 daily intraperitoneal injection of amitriptyline or pregabalin. Microdialysis studies were performed to measure noradrenaline levels after left forepaw capsaicin injection in the left spinal dorsal horn in noninjured rats, SNL rats, and SNL rats that had received 5 daily intraperitoneal injections of amitriptyline or pregabalin. RESULTS: NSIA was dramatically attenuated 5 and 6 weeks after SNL (P < 0.001). The noradrenaline level in the lumbar spinal cord was significantly increased in noninjured rats receiving forepaw injection of capsaicin compared with vehicle injection (P < 0.001), but not in rats 6 weeks after SNL surgery. Five daily intraperitoneal injections of amitriptyline (10 mg/kg/d) or pregabalin (10 mg/kg/d) at 5 weeks after SNL gradually increased the ipsilateral hindpaw withdrawal threshold (P < 0.001). At 6 weeks after SNL, amitriptyline, but not pregabalin, reversed the attenuation of NSIA by SNL (P < 0.001) and increased the spinal noradrenaline level after forepaw injection of capsaicin (P = 0.005). CONCLUSIONS: These data suggest that endogenous analgesia in neuropathic pain states is strongly decreased from a certain time after nerve injury and that amitriptyline reverses the attenuation of endogenous analgesia through effects on the descending noradrenergic system.

Effects of Capsaicin and Carbachol on Secretion From Transplanted Submandibular Glands and Prevention of Duct Obstruction.

PURPOSE: To investigate whether capsaicin and carbachol promote secretion from and prevent duct obstruction in transplanted submandibular glands (SMGs). METHODS: This retrospective cohort study included consecutive patients with severe keratoconjunctivitis sicca and successful SMG transplantation. Patients were divided into 2 groups: an exposed group receiving both capsaicin and carbachol after surgery and an unexposed group receiving neither. Secretion changes in response to capsaicin and carbachol administration were recorded in the exposed group. The main outcome measures were the secretory flow rate and duct obstruction rate in the transplanted SMGs. RESULTS: Forty-four patients (44 eyes) in the unexposed group and 115 patients (128 eyes) in the exposed group were followed up for more than 3 months postoperatively. The baseline characteristics were similar between the groups. The secretory flow rate before and 5, 25, 55 minutes after administration was 1 mm (0-2 mm) (median with interquartile range), 3 mm (1-5 mm), 4 mm (2-5 mm), 1 mm (0-2.5 mm), respectively, for capsaicin and 1 mm (0-3 mm), 1050 mm (450-1500 mm), 375 mm (150-600 mm), 0 mm (0-150 mm), respectively, for carbachol (P < 0.001 for both). In the exposed group, 6.2% of eyes had duct obstruction, whereas 18.2% of eyes in the unexposed group had duct obstruction (P = 0.031) (odds ratio = 0.3, 95% confidence interval, 0.105-0.856). CONCLUSIONS: This study provides evidence that capsaicin and carbachol effectively promote secretion from and prevent duct obstruction in transplanted SMGs during at least 3 months after transplantation.

Tachycardia in response to remote capsaicin injection as a model for nociception in the ball python (Python regius).

OBJECTIVES: To quantify the effect of subcutaneous (SC) capsaicin injection on heart rate (HR) in ball pythons (Python regius) and to assess the efficacy of two opioids (morphine and butorphanol) in modifying this response. STUDY DESIGN: Prospective, randomized, unmatched study. ANIMALS: Eleven mixed-sex, captive-bred ball pythons. METHODS: Snakes were randomly assigned to three groups (n = 6) by intramuscular premedication: 1) control: saline (0.9 mL); 2) morphine (10 mg kg(-1) ); and 3) butorphanol (10 mg kg(-1) ). Three snakes were tested twice and another two were tested three times in different treatments administered 1 month apart. Under isoflurane anaesthesia, snakes were instrumented with SC electrocardiogram (ECG) electrodes and an SC catheter for remote stimulus delivery. After recovery from anaesthesia, all snakes, in visual and audial isolation from the experimenter, received a sham stimulus of saline (0.4 mL) via the SC catheter. A nociceptive stimulus of SC capsaicin (3 mg in 0.2 mL saline with 7% Tween 80) was then applied by catheter at 7 hours after premedication. In a subset (n = 3), two sham injections (saline 0.2 mL) preceded the capsaicin treatment. HR was recorded via ECG, and changes in HR (ΔHR) from baseline were calculated for all stimulations. RESULTS: Capsaicin injection was associated with a significant increase in HR [peak ΔHR: saline group: 8.8 ± 7.1 beats minute(-1) ; capsaicin group: 21.1 ± 5.8 beats minute(-1) (p = 0.0055)] and integrated ΔHR as a function of time. The administration of morphine or butorphanol 7 hours prior to nociception failed to significantly reduce the peak and integrated ΔHR. Butorphanol caused marked, long-lasting sedation as assessed by muscle tone. CONCLUSIONS AND CLINICAL RELEVANCE: The HR response to an SC capsaicin injection can serve as a nociceptive model in P. regius. Morphine and butorphanol administration did not reduce HR response to capsaicin stimulation but produced significantly different effects on pre-stimulation HR and sedation.

Therapeutic role of endoscopic ultrasound in pancreaticobiliary disease: A comprehensive review.

With the development of technology and accessories, the role of endoscopic ultrasound (EUS) has evolved from diagnostics to therapeutics. In order to characterise the therapeutic role of EUS, we searched Web of Knowledge database and reviewed articles associated with therapeutic EUS. There are two modalities for the therapeutic purpose: drainage and fine-needle injection. EUS-guided drainage is a promising procedure for the treatment of peripancreatic fluid collection and biliary obstruction; EUS-guided fine-needle injections such as celiac plexus neurolysis, for the purpose of pain relief for pancreatic cancer and chronic pancreatitis, has emerged as a promising procedure. The aim of the study was to perform a comprehensive and conscientious review on the techniques, complications and clinical outcomes of those EUS-based procedures.

Single high-concentration capsaicin application prevents c-Fos expression in spinothalamic and postsynaptic dorsal column neurons after surgical incision.

BACKGROUND: Allodynia and hyperalgesia present after surgical interventions are often a major complain of surgical patients. It is thought that both peripheral and central mechanisms contribute to these symptoms. In this study, the role of peripheral nerve fibres that express transient receptor potential vanilloid 1 (TRPV1) receptors in the activation of spinothalamic tract (STT) and postsynaptic dorsal column (PSDC) neurons was assessed in a model of surgical pain. METHODS: Spinothalamic tract and PSDC neurons retrogradely labelled from the thalamus and nucleus gracilis were used. Activation of these projection neurons was evaluated after plantar incision as expression of the early gene product, c-Fos protein, in the nuclei of these neurons. RESULTS: There was a robust increase in c-Fos immunopositivity in the STT and PSDC neurons, in the control animals after a plantar incision. This increase in c-Fos expression was significantly attenuated in animals in which a single high-concentration capsaicin injection was made intradermally at the incision site 24 h before the surgery. CONCLUSIONS: Our results suggest that activation of both STT and PSDC neurons is involved in development of pain states present after surgical incision and that TRPV1-containing peripheral nerve fibres are needed for c-Fos expression in these dorsal horn neurons after plantar incision.

Nociceptor-selective peripheral nerve block induces delayed mechanical hypersensitivity and neurotoxicity in rats.

BACKGROUND: Long-lasting, sensory-specific peripheral nerve blockade would advance perioperative analgesia. Perineural injection of a combination of transient receptor potential vanilloid 1 channel agonists and lidocaine or its hydrophilic derivative, QX-314, produces prolonged sensory or nociceptor-selective nerve block in rodents. In this study, the authors tested the efficacy of these combinations in peripheral nerve block after incisional surgery in rats. METHODS: The authors administered perisciatic lidocaine (2%), QX-314 (0.2%) followed by dilute capsaicin (0.05%, 10 min later), or vehicle in rats and the duration of motor and sensory block to thermal and mechanical stimuli assessed in normal animals and those after incisional surgery to the hind paw. Other animals receiving these injections were evaluated 7 weeks later by behavior and histology for potential neurotoxicity. RESULTS: Perineural injection of the combination not only attenuated mechanical hypersensitivity for 72 h after incision but also resulted in delayed onset mechanical hypersensitivity several weeks later, accompanied by degeneration of central terminals of isolectin B4 (nonpeptidergic) and calcitonin gene-related peptide-containing (peptidergic) afferents in the ipsilateral spinal cord. Dorsal root ganglia ipsilateral to injection of the combination showed increased expression of activating transcription factor-3 and satellite cell activation. CONCLUSIONS: Combined administration of local anesthetics with the transient receptor potential vanilloid 1 agonist capsaicin induced a near complete blockade of incision-induced hypersensitivity for several days. However, the same combination induced delayed mechanical hypersensitivity and neurotoxicity in naïve rats. Combination of these drugs in these concentrations is likely to result in neurotoxicity, and the safety of other concentrations warrants further study.

Capsaicin treatment reduces nasal hyperreactivity and transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) overexpression in patients with idiopathic rhinitis.

BACKGROUND: Idiopathic rhinitis (IR) is a prevalent condition for which capsaicin nasal spray is the most effective treatment. However, the mechanisms underlying IR and the therapeutic action of capsaicin remain unknown. OBJECTIVE: We sought to investigate the molecular and cellular bases of IR and the therapeutic action of capsaicin. METHODS: Fourteen patients with IR and 12 healthy control subjects (HCs) were treated with intranasal capsaicin. The therapeutic effect was assessed in patients with IR by using visual analog scale and therapeutic response evaluation scores, and nasal hyperreactivity was evaluated by means of cold dry air provocation. Nasal samples served to measure the levels of neuromediators and expression of chemosensory cation channels, protein gene product 9.5 (PGP 9.5), and the mast cell marker c-kit. The effects of capsaicin were also tested in vitro on human nasal epithelial cells and mast cells. RESULTS: Patients with IR had higher baseline transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) expression in the nasal mucosa and higher concentrations of substance P (SP) in nasal secretions than HCs. Symptomatic relief was observed in 11 of 14 patients with IR after capsaicin treatment. Expression of TRPV1; transient receptor potential cation channel subfamily M, receptor 8 (TRPM8); and PGP 9.5 was only reduced in patients with IR after capsaicin treatment. Capsaicin did not alter c-KIT expression or nasal epithelial morphology in patients with IR and HCs nor did it induce apoptosis or necrosis in cultured human nasal epithelial cells and mast cells. CONCLUSION: IR features an overexpression of TRPV1 in the nasal mucosa and increased SP levels in nasal secretions. Capsaicin exerts its therapeutic action by ablating the TRPV1-SP nociceptive signaling pathway in the nasal mucosa.

Pain fiber anesthetic reduces brainstem Fos after tooth extraction.

We recently demonstrated that pain-sensing neurons in the trigeminal system can be selectively anesthetized by co-application of QX-314 with the TRPV1 receptor agonist, capsaicin (QX cocktail). Here we examined whether this new anesthetic strategy can block the neuronal changes in the brainstem following molar tooth extraction in the rat. Adult male Sprague-Dawley rats received infiltration injection of anesthetic 10 min prior to lower molar tooth extraction. Neuronal activation was determined by immunohistochemistry for the proto-oncogene protein c-Fos in transverse sections of the trigeminal subnucleus caudalis (Sp5C). After tooth extraction, c-Fos-like immunoreactivity (Fos-LI) detected in the dorsomedial region of bilateral Sp5C was highest at 2 hrs (p < .01 vs. naïve ipsilateral) and declined to pre-injury levels by 8 hrs. Pre-administration of the QX cocktail significantly reduced to sham levels Fos-LI examined 2 hrs after tooth extraction; reduced Fos-LI was also observed with the conventional local anesthetic lidocaine. Pulpal anesthesia by infiltration injection was confirmed by inhibition of the jaw-opening reflex in response to electrical tooth pulp stimulation. Our results suggest that the QX cocktail anesthetic is effective in reducing neuronal activation following tooth extraction. Thus, a selective pain fiber 'nociceptive anesthetic' strategy may provide an effective local anesthetic option for dental patients in the clinic.

The capsaicin 8% patch for neuropathic pain in clinical practice: a retrospective analysis.

OBJECTIVE: To investigate the response of patients with peripheral neuropathic pain (PNP) to capsaicin 8% patch treatment in a clinical setting. DESIGN: Retrospective analysis. SETTING: The Clinic for Pain Therapy and Palliative Medicine at the Medical Centre for the region of Aachen, Germany. SUBJECTS: Patients diagnosed with PNP who attended the clinic for capsaicin 8% patch treatment between January 13, 2010 and February 7, 2011. OUTCOME MEASURES: Pain intensity was assessed using the Numeric Pain Rating Scale (NPRS) at baseline and following each capsaicin 8% patch treatment. Changes in prescribed concomitant neuropathic pain (NP) medications and response duration were recorded. RESULTS: Overall, 68 patients with PNP conditions, including facial neuropathy (severe trigeminal neuralgia in V2), polyneuropathy, post-herpetic neuralgia, and mononeuropathies, received 96 treatments with the capsaicin 8% patch. The 53 patients with a follow-up of ≥8 weeks demonstrated a 48.4% mean reduction in NPRS score from baseline to Weeks 1-8. Among the 37 responders (those exhibiting ≥30% reduction in NPRS score from baseline to Weeks 1-8), the median time to re-treatment was 125 days. Following treatment, there was a significant (P < 0.001) 54% reduction in the mean number of prescribed concomitant NP medications taken by patients. CONCLUSIONS: This analysis demonstrates that in clinical practice, the capsaicin 8% patch provides rapid and sustained pain reductions in patients with a variety of PNP conditions and a significant reduction in prescribed concomitant NP medications. The capsaicin 8% patch can be a valuable addition to the NP treatment armory for certain patients.

Day surgery, variations in routines and practices a questionnaire survey.

BACKGROUND: Day surgery is expanding however little is known about every day practice and routines. METHODS: A web-based questionnaire including 34 questions with fixed multiple choice responses around routine and practice for the perioperative handling of patients scheduled for day case surgery was send to 100 hospitals. RESULTS: There was an overall response rate of 70%. Most centres had a dedicated day surgery unit (87%). Preoperative assessment routines, when, how and by whom varied. Patient self-assessment questionnaires were common practice (87%). Upper age limit was uncommon (10%), lower age limit common (77%), and fixed high body mass index-limitation showed a mixed pattern, mean 40%. Postoperative nauseas and vomiting-risk stratification varied mean 46%. Anxiolytic premedication was uncommon. Administration of oral analgesics varied, mean 70%; paracetamol (94%), NSAIDs (80%) and opioid (28%). Preferred general anaesthesia technique varied considerable. Laryngeal mask airway was consistently used. Management of pain while in hospital was consistently performed. A majority centres provided take-home analgesics "tablet-package" (69%) or as prescription (80%). Strong opioids to be taken at home were given or prescribed by 59% of units. Written information about the postoperative care was common practice (90%), written instruction about management of pain was less frequently provided (69%). Most hospitals (93%) had standardised discharge criteria, including demand of an escort (75%) and not being alone first postoperative night (81%). CONCLUSIONS: We found that regime for day surgical anaesthesia practice varied between as well as within countries. There is obvious room for further research on how to achieve safe and cost-effective logistics and practice for day case surgery.

Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients.

The purpose of this study was to evaluate the short-term efficacy of topical capsaicin treatment in patients severely affected by fibromyalgia. One hundred and thirty fibromyalgia patients were randomly divided into two groups. The control group, 56 women and 4 men who continued their medical treatment, and the capsaicin group, 70 women who apart from continuing their medical treatment, also underwent topical capsaicin 0.075 % 3 times daily for 6 weeks. At the beginning of the program, there were no significant differences between the two groups in any of the analyzed parameters. At the end of the treatment, there were significant improvements in the capsaicin group in the myalgic score (5.21 vs 3.8, p = 0.02) and global subjective improvement (22.8 vs 5 %, p = 0.001). Six weeks after the end of the treatment, the experimental group showed significant differences in Visual Analogue Scale of depression (5.63 vs 7.35, p = 0.02), Fibromyalgia Impact Questionnaire (67.89 vs 77.7, p = 0.02), role limitations due to emotional problems (36.17 vs 17.2, p = 0.05), Fatigue Severity Scale (6.2 vs 6.6, p = 0.04), myalgic score (3.94 vs 2.66, p = 0.02) and pressure pain threshold (79.25 vs 56.71, p = 0.004). In conclusion, patients severely affected by fibromyalgia can obtain short-term improvements following topical capsaicin 0.075 % treatment three times daily for 6 weeks.

Sensory dysfunction of bladder mucosa and bladder oversensitivity in a rat model of metabolic syndrome.

PURPOSE: To study the role of sensory dysfunction of bladder mucosa in bladder oversensitivity of rats with metabolic syndrome. MATERIALS AND METHODS: Female Wistar rats were fed a fructose-rich diet (60%) or a normal diet for 3 months. Based on cystometry, the fructose-fed rats (FFRs) were divided into a group with normal detrusor function or detrusor overactivity (DO). Acidic adenosine triphosphate (ATP) solution (5mM, pH 3.3) was used to elicit reflex micturition. Cystometric parameters were evaluated before and after drug administration. Functional proteins of the bladder mucosa were assessed by western blotting. RESULTS: Compared to the controls, intravesical acidic ATP solution instillation induced a significant increase in provoked phasic contractions in both FFR groups and a significant decrease in the mean functional bladder capacity of group DO. Pretreatment with capsaicin for C-fiber desentization, intravesical liposome for mucosal protection, or intravenous pyridoxal 5-phosphate 6-azophenyl-2',4'-disulfonic acid for antagonized purinergic receptors can interfere with the urodynamic effects of intravesical ATP in FFRs and controls. Over-expression of TRPV1, P2X(3), and iNOS proteins, and down-regulation of eNOS proteins were observed in the bladder mucosa of both fructose-fed groups. CONCLUSIONS: Alterations of sensory receptors and enzymes in the bladder mucosa, including over-expression of TRPV1, P2X(3), and iNOS proteins, can precipitate the emergence of bladder phasic contractions and oversensitivity through the activation of C-afferents during acidic ATP solution stimulation in FFRs. The down-regulation of eNOS protein in the bladder mucosa of FFRs may lead to a failure to suppress bladder oversensitivity and phasic contractions. Sensory dysfunction of bladder mucosa and DO causing by metabolic syndrome are easier to elicit bladder oversensitivity to certain urothelium stimuli.

Effect of capsaicin supplementation on repeated sprinting performance.

Performance in many team sports is partially dependent on the ability to perform repeatedly at high intensity. Previous research demonstrates that capsaicin (CAP) has physiological and metabolic effects that could influence exercise performance and inflammation. The purpose of this study was to investigate the influence of CAP on performance of and the interleukin-6 (IL-6) response to repeated sprints. Nineteen healthy male experienced athletes, age 18-30 years, participated in a placebo (PCB)-controlled, crossover study. During 1 trial, they consumed 3 g·d(-1) cayenne (25.8 mg·d(-1) CAP) and the other a PCB for days. Directly after the supplementation period, they completed a repeated sprint test (RST) consisting of 15 30-m maximal effort sprints on 35-second intervals with sprint times measured via an electronic dual-beam timing system. Fasted blood draws for IL-6 were taken at baseline before supplementation, 45 minute pre-RST, and immediately post-RST. Rate of perceived exertion (RPE), muscle soreness (MS), and gastrointestinal distress (GD) for 5 symptom subscales were measured 1-minute pretest, during, posttest, and 1-minute posttest. The MS was additionally measured for 3-day posttest. Relative to the PCB, CAP significantly increased the sum of ratings of GD symptoms by 6.3-fold. There was no difference between treatments in fastest or mean sprint time, fatigue, IL-6 response, RPE, or MS. In summary, CAP did not influence repeated sprint performance or the IL-6 response but caused substantial GD. The CAP is not recommended for athletes involved in repeated sprinting.

Capsaicin instillation for postoperative pain following total knee arthroplasty: a preliminary report of a randomized, double-blind, parallel-group, placebo-controlled, multicentre trial.

BACKGROUND: Pain following total knee arthroplasty (TKA) interferes with rehabilitation. Capsaicin applied in high concentration to nociceptors can cause relatively selective C-fibre desensitization for a period of weeks to months. Resultant long-lasting analgesia might facilitate rehabilitation. OBJECTIVE: The objective of this study was to determine if direct instillation of a high-concentration capsaicin preparation into the wound following TKA would provide pain relief, improve physical functioning and rehabilitation, and reduce opioid requirements. METHODS: This was a randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase II trial carried out in a teaching hospital system. Non-opioid-tolerant males or females aged 18-85 years with a body mass index (BMI) ≤45 kg/m2, American Society of Anesthesiologists (ASA) physical status 1-3 and end-stage osteoarthritis who were scheduled for primary unilateral TKA were included. Patients received placebo vehicle or capsaicin 15 mg (Anesiva 4975) by instillation immediately prior to wound closure. Surgery was conducted under spinal anaesthesia and femoral nerve block. Postoperative rescue analgesia consisted of intravenous patient-controlled analgesia with morphine for 24 hours; oral oxycodone was provided thereafter as needed. It was hypothesized prior to data collection that capsaicin instillation would reduce postoperative pain scores and result in improved patient satisfaction and ambulation. The primary outcome was the area under the numerical rating scale (NRS) for pain score-time curve from 4 to 24 hours (AUC(4-24)). NRS for pain scores were obtained every 4 hours for 24 hours then daily with ambulation and physical therapy for 3 days. Function and patient satisfaction were assessed at 14, 28 and 42 days. RESULTS: Data from 14 patients (seven per group) from a single centre (data were not available from other sites because of sponsor bankruptcy) were available for this preliminary report. AUC(4-24) was not significantly different clinically (placebo 70.3; capsaicin 65.7) in this sample; however, a significant opioid-sparing effect was seen in the capsaicin group despite the fact that patients in this group had higher BMIs. Pain scores tended to be lower in the capsaicin group, despite the fact that patients in this group received significantly less rescue opioid medication. Morphine use from 12-24 hours was lower (capsaicin group mean 13.4 mg; 95% confidence interval [CI] 7.4, 19.5; range 10-21 mg vs placebo group mean 25.9 mg; 95% CI 19.8, 32.0; range 15-36 mg; p = 0.009). Total intravenous and oral opioid in morphine equivalents over 72 hours was also lower with capsaicin compared with placebo (p = 0.03). Active range of motion (ROM) was also significantly improved at day 14 in the capsaicin group compared with the placebo group (p = 0.0014). A higher percentage of patients in the capsaicin group reported being extremely satisfied with their treatment. The only statistically significant difference in treatment-emergent adverse events was for pruritus, which was more frequent in the placebo group (p = 0.03). CONCLUSION: Despite having higher BMIs, patients in the capsaicin group achieved comparable or better pain scores with significantly less opioid use in the first 3 postoperative days. They also had less pruritus, which may have been a consequence of the opioid-sparing effect. The effects of capsaicin with respect to function, however, appeared to be longer lasting, with improved active ROM reported at 14 days.