The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown. Our previous study showed that neonatal maternal deprivation (NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors (AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion (DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall, our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β adrenergic signaling in DRGs.
Adrenergic Agents ; pharmacology ; Animals ; Ganglia, Spinal ; drug effects ; Hyperalgesia ; drug therapy ; physiopathology ; Hypersensitivity ; drug therapy ; Male ; Maternal Deprivation ; Neurons ; drug effects ; Patch-Clamp Techniques ; methods ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Stress, Physiological ; physiology ; Visceral Pain ; chemically induced ; metabolism

Two new sesquiterpenes, trivially named ricinusoids A (1) and ricinusoids B (2), were isolated from ethyl acetate fraction of Ricinus communis. The structures of new compounds were elucidated by detailed spectroscopic techniques, including 1D- and 2D-NMR, UV, IR spectroscopy, and mass spectrometry. The compounds (1-2) were also assessed for in-vivo sedative and analgesic like effects in open field and acetic acid induced writhing tests respectively at 5, 10, and 20 mg·kg i.p. Pretreatment of both test compounds caused significant (P ≤ 0.05) reduction in locomotive activity like sedative agents and abdominal constrictions like analgesics. Both compounds (1-2) possessed marked sedative and antinociceptive effects in animal models.
Analgesics ; administration & dosage ; chemistry ; isolation & purification ; Animals ; Humans ; Hypnotics and Sedatives ; administration & dosage ; chemistry ; isolation & purification ; Locomotion ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Structure ; Pain ; drug therapy ; physiopathology ; Plant Extracts ; administration & dosage ; chemistry ; isolation & purification ; Plant Leaves ; chemistry ; Ricinus ; chemistry ; Sesquiterpenes ; administration & dosage ; chemistry ; isolation & purification

Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia, where two different contexts (dark and bright) were matched with a high (52°C) or low (48°C) temperature in the hot-plate test during training. Before and after training, we set the temperature to the high level in both contexts. Rats showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone (an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.
Action Potentials ; drug effects ; physiology ; Analgesics ; pharmacology ; therapeutic use ; Animals ; Disease Models, Animal ; Electric Stimulation ; Female ; In Vitro Techniques ; Naloxone ; pharmacology ; Narcotic Antagonists ; pharmacology ; Optogenetics ; Pain ; drug therapy ; pathology ; physiopathology ; Pain Measurement ; drug effects ; Pain Threshold ; drug effects ; physiology ; Patch-Clamp Techniques ; Physical Stimulation ; Prefrontal Cortex ; drug effects ; metabolism ; pathology ; Pyramidal Cells ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Time Factors

The pain peptide adrenomedullin (AM) plays a pivotal role in pathological pain. The present study was designed to investigate the effect of blockade of AM receptor on bone cancer pain (BCP) and its mechanism. BCP was developed by inoculation of Walker 256 mammary gland carcinoma cells in the tibia medullary cavity of Sprague Dawley rats. The selective AM receptor antagonist AMwas administered intrathecally on 15 d after the inoculation. Quantitative real-time PCR was used to detect mRNA level of CC chemokine ligand 2 (CCL2) in dorsal root ganglion (DRG). Double immunofluorescence staining was used to analyze the localizations of CCL2 and AM in DRG of normal rats. The results showed that, from 6 to15 d after the inoculation, the animals showed significant reduction in the mechanical pain threshold in the ipsilateral hindpaw, companied by the decline in bone density of tibia bone. The expression of CCL2 mRNA in DRG of BCP rats was increased by 3 folds (P < 0.001 vs saline group). Intrathecal administration of AMabolished bone cancer-induced mechanical allodynia and increase of CCL2 mRNA level (P < 0.001). In normal rats, CCL2 was co-localized with AM in DRG neurons. These results suggest that AM may play a role in the pathogenesis of BCP. The increased AM bioactivity up-regulates CCL2 expression in DRG, which may contribute to the induction of pain hypersensitivity in bone cancer.
Adrenomedullin ; administration & dosage ; pharmacology ; Animals ; Bone Neoplasms ; drug therapy ; Chemokine CCL2 ; metabolism ; Ganglia, Spinal ; physiopathology ; Hyperalgesia ; drug therapy ; Pain ; drug therapy ; Pain Threshold ; Peptide Fragments ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Receptors, Adrenomedullin ; antagonists & inhibitors

BACKGROUND: Although both pregabalin and gabapentin are known to be useful for treating lumbar radiating pain and reducing the incidence of surgery, the oral corticosteroids sometimes offer a dramatic effect on severe radiating pain despite the lack of scientific evidence. METHODS: A total of 54 patients were enrolled among 703 patients who complained of lumbar radiating pain. Twenty patients who received an oral corticosteroid was classified as group A and 20 patients who received the control drugs (pregabalin or gabapentin) as group B. Oswestry Disability Index (ODI), Revised Roland Morris disability questionnaire (RMDQ), Short Form 36 (SF-36) questionnaire, lumbar radiating pain, objective patient satisfaction, and objective improvement of patients or physicians were assessed at 2, 6, and 12 weeks after medication. RESULTS: No difference in the sex ratio and age was observed between the groups (p = 0.70 and p = 0.13, respectively). Group A showed greater improvement in radiating pain after 2, 6, and 12 weeks than group B (p < 0.001, p = 0.001, and p < 0.001, respectively). No differences were observed between the groups in satisfaction at the beginning and 12 weeks after taking the medication (p = 0.062 and p = 0.061, respectively) and in objective improvement of patients and physicians (p = 0.657 and p = 0.748, respectively). Group A was less disabled and had greater physical health scores than group B (p = 0.014 and p = 0.017, respectively). CONCLUSIONS: Oral corticosteroids for the treatment of lumbar radiating pain can be more effective in pain relief than gabapentin or pregabalin. The satisfaction of patients and physicians with the drug and objective improvement status were not inferior to that with gabapentin or pregabalin.
Adolescent ; Adrenal Cortex Hormones/*therapeutic use ; Adult ; Aged ; Amines/therapeutic use ; Analgesics/therapeutic use ; Cyclohexanecarboxylic Acids/therapeutic use ; Female ; Humans ; Low Back Pain/*drug therapy/*physiopathology ; Lumbosacral Region/physiopathology ; Male ; Middle Aged ; Patient Satisfaction/statistics & numerical data ; Pregabalin/therapeutic use ; Quality of Life ; Radiculopathy/drug therapy ; Surveys and Questionnaires ; Young Adult ; gamma-Aminobutyric Acid/therapeutic use

Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD50), median effective dose (ED50) and half maximal inhibitory concentration (IC50) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti-inflammatory and analgesic effects and it may help reduce the damage of ALI.
Acetic Acid ; Acute Lung Injury ; chemically induced ; drug therapy ; pathology ; Analgesics ; pharmacology ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Carrageenan ; administration & dosage ; Chlorogenic Acid ; pharmacology ; Dinoprostone ; antagonists & inhibitors ; biosynthesis ; Disease Models, Animal ; Dosage Forms ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Ear ; pathology ; Edema ; chemically induced ; drug therapy ; pathology ; Flavonoids ; pharmacology ; Lipopolysaccharides ; administration & dosage ; Male ; Mice ; Mice, Inbred Strains ; Pain ; chemically induced ; drug therapy ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Xylenes ; administration & dosage

Although the development of the 2009 SpA classification criteria by Assessment of SpondyloArthritis international Society (ASAS) represents an important step towards a better definition of the early disease stage particularly in axial spondyloarthritis (axSpA), the specificity of the criteria has been criticized these days. As the commonest zoonotic infection worldwide, human brucellosis can mimic a large number of diseases, including SpA. This study was performed to determine the frequency of rheumatologic manifestations in patients with brucellosis and the chance of misdiagnosing them as having axSpA in central China. The results showed that clinical manifestations of axSpA could be observed in brucellosis. Over half of patients had back pain, and one fifth of the patients with back pain were less than 45 years old at onset and had the symptom for more than 3 months. Two young males were falsely classified as suffering from axSpA according to the ASAS criteria, and one with MRI proved sacroiliitis was once given Etanercept for treatment. Therefore, differential diagnosis including human brucellosis should always be kept in mind when applying the ASAS criteria, even in traditionally non-endemic areas.
Adult ; Aged ; Antirheumatic Agents ; therapeutic use ; Back Pain ; physiopathology ; Brucellosis ; diagnosis ; drug therapy ; physiopathology ; China ; Diagnosis, Differential ; Diagnostic Errors ; prevention & control ; statistics & numerical data ; Etanercept ; therapeutic use ; Female ; Humans ; Inappropriate Prescribing ; statistics & numerical data ; Male ; Middle Aged ; Practice Guidelines as Topic ; Rheumatologists ; ethics ; Sacroiliitis ; physiopathology ; Spondylarthritis ; diagnosis ; drug therapy ; physiopathology

Adhesive capsulitis is a common cause of shoulder pain and limited movement. The objectives of this review were to assess the efficacy and safety of corticosteroid injections for adhesive capsulitis and to evaluate the optimum dose and anatomical site of injections. PubMed and CENTRAL databases were searched for randomised trials and a total of ten trials were included. Results revealed that corticosteroid injection is superior to placebo and physiotherapy in the short-term (up to 12 weeks). There was no difference in outcomes between corticosteroid injection and oral nonsteroidal anti-inflammatory drugs at 24 weeks. Dosages of intra-articular triamcinolone 20 mg and 40 mg showed identical outcomes, while subacromial and glenohumeral corticosteroid injections had similar efficacy. The use of corticosteroid injections is also generally safe, with infrequent and minor side effects. Physicians may consider corticosteroid injection to treat adhesive capsulitis, especially in the early stages when pain is the predominant presentation.
Adrenal Cortex Hormones ; pharmacology ; Bursitis ; complications ; drug therapy ; therapy ; Female ; Humans ; Injections ; Male ; Pain ; complications ; Physical Therapy Modalities ; Primary Health Care ; Randomized Controlled Trials as Topic ; Shoulder ; physiopathology ; Shoulder Joint ; physiopathology ; Treatment Outcome ; Visual Analog Scale

PURPOSE: To compare pain scores of patients during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection procedures. METHODS: Seventy eyes of 70 patients who had not previously undergone intravitreal anti-vascular endothelial growth factor therapy were included in this study. Thirty-five patients received ranibizumab and 35 patients received bevacizumab. The diagnoses of the patients were: 27 age related macular degeneration, 15 diabetic macular edema, 9 diabetic vitreous hemorrhage, 6 central retinal vein occlusion, 11 branch retinal vein occlusion and 2 central serous chorioretinopathy. Bevacizumab (1.25 mg/0.05 mL) was injected into the vitreous cavity using a 27-gauge needle, and ranibizumab (0.5 mg/0.05 mL) was injected with 30-gauge needle. Patients were asked just after the injection to rate their perceived pain during the injection using the visual analogue scale (VAS) of 0 (no pain) to 10 (unbearable/worst pain). The average of these scores was used as the primary outcome. RESULTS: The VAS pain scores in the ranibizumab and bevacizumab groups were 1.06 +/- 0.91 (range, 0 to 3) and 1.94 +/- 1.55 (range, 0 to 7), respectively, a significant difference (p = 0.005). Patients <65 and > or =65 years of age in both the ranibizumab and bevacizumab groups were then compared. For patients <65, there was a significant difference in the average VAS pain scores between groups (p = 0.003). However, for patients > or =65 years, there was not a significant difference in the average VAS pain scores between groups (p = 0.238). Female and male patients in both ranibizumab and bevacizumab groups were also compared. For female patients, there was a significant difference in the average VAS pain scores between groups (p = 0.016), although not for male patients (p = 0.078). CONCLUSIONS: Thirty-gauge intravitreal injection is more comfortable than 27-gauge injection. Injection of bevacizumab with 30-gauge needle syringes may be more tolerable for patients.
Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Bevacizumab/*administration & dosage ; Diabetic Retinopathy/drug therapy/physiopathology ; Female ; Humans ; *Intravitreal Injections ; Macular Degeneration/drug therapy/physiopathology ; Macular Edema/drug therapy/physiopathology ; Male ; Middle Aged ; Pain Measurement ; Ranibizumab/*administration & dosage ; Retinal Vein Occlusion/drug therapy/physiopathology

PURPOSE: To compare pain scores of patients during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection procedures. METHODS: Seventy eyes of 70 patients who had not previously undergone intravitreal anti-vascular endothelial growth factor therapy were included in this study. Thirty-five patients received ranibizumab and 35 patients received bevacizumab. The diagnoses of the patients were: 27 age related macular degeneration, 15 diabetic macular edema, 9 diabetic vitreous hemorrhage, 6 central retinal vein occlusion, 11 branch retinal vein occlusion and 2 central serous chorioretinopathy. Bevacizumab (1.25 mg/0.05 mL) was injected into the vitreous cavity using a 27-gauge needle, and ranibizumab (0.5 mg/0.05 mL) was injected with 30-gauge needle. Patients were asked just after the injection to rate their perceived pain during the injection using the visual analogue scale (VAS) of 0 (no pain) to 10 (unbearable/worst pain). The average of these scores was used as the primary outcome. RESULTS: The VAS pain scores in the ranibizumab and bevacizumab groups were 1.06 +/- 0.91 (range, 0 to 3) and 1.94 +/- 1.55 (range, 0 to 7), respectively, a significant difference (p = 0.005). Patients <65 and > or =65 years of age in both the ranibizumab and bevacizumab groups were then compared. For patients <65, there was a significant difference in the average VAS pain scores between groups (p = 0.003). However, for patients > or =65 years, there was not a significant difference in the average VAS pain scores between groups (p = 0.238). Female and male patients in both ranibizumab and bevacizumab groups were also compared. For female patients, there was a significant difference in the average VAS pain scores between groups (p = 0.016), although not for male patients (p = 0.078). CONCLUSIONS: Thirty-gauge intravitreal injection is more comfortable than 27-gauge injection. Injection of bevacizumab with 30-gauge needle syringes may be more tolerable for patients.
Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Bevacizumab/*administration & dosage ; Diabetic Retinopathy/drug therapy/physiopathology ; Female ; Humans ; *Intravitreal Injections ; Macular Degeneration/drug therapy/physiopathology ; Macular Edema/drug therapy/physiopathology ; Male ; Middle Aged ; Pain Measurement ; Ranibizumab/*administration & dosage ; Retinal Vein Occlusion/drug therapy/physiopathology