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1.
Physiother Theory Pract ; 38(10): 1519-1527, 2022 Oct.
Article in English | MEDLINE | ID: mdl-33267720

ABSTRACT

BACKGROUND: Body mass index, pain, female sex, and age have been reported as predictors of physical activity in patients with lumbar spinal stenosis (LSS). However, no reports have examined the psychological factors associated with physical activity in people with LSS. PURPOSE: To use psychological assessments to identify the factors associated with physical activity measured as daily step count in people with LSS. METHODS: Seventy-one patients who received outpatient physical therapy were included. All patients completed the following scales at baseline: Zurich Claudication Questionnaire; self-paced walking test (SPWT); numerical rating scale of low back pain, leg pain, and leg numbness; Hospital Anxiety and Depression Scale (HADS); Pain Catastrophizing Scale; Pain Anxiety Symptoms Scale (PASS-20); and Tampa Scale for Kinesiophobia. Physical activity was measured using a pedometer as the average number of daily steps. RESULTS: Daily step count was significantly associated with age, number of stenoses, severity of stenosis at L3-L4, walking distance on the SPWT, PASS-20 total score, cognitive anxiety, escape/avoidance, fear, and HADS depression score (p < .05). Multiple regression analysis showed that age, severity of stenosis at L3-L4, walking distance on the SPWT, and PASS-20 fear predicted daily step count (r2 = 0.414). CONCLUSION: Older age, fewer stenoses, less severe stenosis at L3-L4, lower walking capacity, higher anxiety, and fear-avoidance beliefs about pain and depression are more closely associated with lower daily step count than are back and leg pain. Assessment and treatment of psychological factors might help to increase physical activity in patients with LSS.


Subject(s)
Low Back Pain , Spinal Stenosis , Constriction, Pathologic/complications , Female , Humans , Low Back Pain/complications , Low Back Pain/therapy , Lumbar Vertebrae , Spinal Stenosis/complications , Walking
2.
Asian Spine J ; 16(2): 270-278, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34015209

ABSTRACT

STUDY DESIGN: A retrospective study of prospectively collected clinical data. PURPOSE: To identify preoperative psychological factors associated with patient satisfaction after surgery for lumbar spinal stenosis (LSS). OVERVIEW OF LITERATURE: Associations between depressive symptoms, anxiety, and worse surgical outcome or patient dissatisfaction have been reported in LSS patients. However, the influence of preoperative pain catastrophizing and fear-avoidance beliefs on postoperative satisfaction is not well understood. METHODS: LSS patients who underwent decompression surgery with or without fusion were included. Clinical outcomes were measured before surgery and 6 months postoperatively using the Zurich Claudication Questionnaire (ZCQ); Visual Analog Scale (VAS) of low back pain, leg pain, and leg numbness; Japanese Orthopaedic Association Back Pain Evaluation Questionnaire; and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). The Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale, and Pain Anxiety Symptoms Scale were used to evaluate psychological status before surgery. Patients were classified as satisfied or dissatisfied with surgery based on a ZCQ satisfaction subscale cutoff score of 2.5. RESULTS: The satisfied and dissatisfied groups contained 128 and 29 patients, respectively. Six months postoperatively, outcome scores for the dissatisfied group were unchanged or worse than preoperative scores (p>0.05). Multivariate logistic regression analysis showed significant associations between dissatisfaction and preoperative low back pain VAS score ≥ median (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.10-0.74; p=0.01), preoperative mental health SF-36 score ≥ median (OR, 0.26; 95% CI, 0.08-0.89; p=0.03), and preoperative anxiety HADS score ≥ median (OR, 3.95; 95% CI, 1.16-13.46; p=0.03). CONCLUSIONS: Preoperative less severe low back pain, lower mental health, and higher anxiety are associated with patient dissatisfaction with lumbar surgery, not depression, pain catastrophizing, or fear-avoidance beliefs. Pre- and postoperative psychological status should be assessed carefully and managed appropriately.

3.
Clin Rehabil ; 35(7): 964-975, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33423549

ABSTRACT

OBJECTIVE: To compare the 1-year outcomes of patients with lumbar spinal stenosis treated with supervised physical therapy or unsupervised exercise. DESIGN: A single-center randomized controlled trial with concealed allocation, blinded assessor and intention-to-treat analysis. SETTING: Spine care center. SUBJECTS: A total of 86 patients presenting with symptoms of neurogenic claudication caused by lumbar spinal stenosis. INTERVENTIONS: The physical therapy group received supervised physical therapy sessions twice a week for 6 weeks and home exercise program. The home exercise group received 6-week home exercise program only. MAIN MEASURES: The primary outcome was symptom severity on the Zurich claudication questionnaire at 1 year. Secondary outcomes included physical function, pain, health-related quality of life and the surgery rate after 1 year. RESULTS: At 1 year, more patients in the physical therapy group than in the home exercise group achieved minimum clinically important differences in Zurich claudication questionnaire symptom severity (60.5% vs 32.6%; adjusted odds ratio [AOR] 4.3, [95% CI [1.5-12.3], P = 0.01); Zurich claudication questionnaire physical function (55.8% vs 32.6%; AOR 3.0 [1.1-8.1], P = 0.03); SF-36 bodily pain (48.8% vs 25.6%; AOR 2.8 [1.1-7.3], P = 0.03), and SF-36 general health (20.9% vs 7.0%; AOR 6.1 [1.1-33.0], P = 0.04). The surgery rate at 1 year was lower in the physical therapy than in the home exercise group (7.0% vs 23.3%; AOR 0.2 [0.04-0.9] P = 0.04). CONCLUSIONS: Supervised physical therapy produced greater improvements in symptom severity and physical function than unsupervised exercise and was associated with lower likelihood of receiving surgery within 1 year.


Subject(s)
Exercise Therapy , Lumbar Vertebrae/physiopathology , Physical Therapy Modalities , Spinal Stenosis/rehabilitation , Aged , Female , Follow-Up Studies , Humans , Intention to Treat Analysis , Male , Minimal Clinically Important Difference , Orthopedic Procedures/statistics & numerical data , Pain Measurement , Quality of Life , Severity of Illness Index , Spinal Stenosis/physiopathology
4.
Asian Spine J ; 15(4): 533-538, 2021 Aug.
Article in English | MEDLINE | ID: mdl-32872753

ABSTRACT

STUDY DESIGN: Cross-sectional study. PURPOSE: The purpose of this study was to investigate the effects of psychotic symptoms such as anxiety and fear in patients undergoing lumbar spinal canal stenosis. OVERVIEW OF LITERATURE: Recently, patients with spinal disorders have not only been evaluated objectively for their disease, but also for patient-reported outcomes (PROs) including pain, physical function, and quality of life (PROs). Since depression has been previously associated with surgical outcomes, several studies have indicated that psychological problems may worsen the effects of pain and make treatment increasingly difficult. METHODS: A questionnaire survey was conducted on 346 lumbar spinal stenosis (LSS) patients who visited our hospital from 2010 to 2016. The content of the questionnaire included questions on PROs (Japanese Orthopedic Association Back Pain Evaluation Questionnaire [JOABPEQ], Roland-Morris Disability Questionnaire, Japanese version [RDQ], and Zurich Claudication Questionnaire [ZCQ]) and psychological evaluation (Self-rating Questionnaire of Depression, Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale-20 [PASS-20], Hospital Anxiety and Depression Scale, and Brief Scale for Psychiatric Problems in Orthopedic Patients). IBM SPSS Statistics (IBM Corp., Armonk, NY, USA) was used for statistical analysis and Spearman's rank correlation coefficient, Mann-Whitney U-test, and multiple regression analysis were also performed. RESULTS: No significant correlations were found between psychological factors and PROs (r>0.4). However, patients with abnormal scores for preoperative psychological items on questionnaires other than the PASS-20 also had lower scores for lumbar spine dysfunction and social life dysfunction on the JOABPEQ subscales along with higher scores for the RDQ, symptom severity and physical function on the ZCQ compared to those with normal psychological scores (p<0.05). CONCLUSIONS: Preoperative psychological factors in patients with LSS were associated with their RDQ, JOABEPQ, and ZCQ scores. These results suggest that factors such as catastrophic thoughts on pain, anxiety, depression, and fear that may affect the clinical outcomes in patients with LSS should be evaluated before surgery to facilitate psychological interventions.

5.
Spine Surg Relat Res ; 4(3): 247-255, 2020.
Article in English | MEDLINE | ID: mdl-32864492

ABSTRACT

INTRODUCTION: Sarcopenia, a condition characterized by decreased skeletal muscle mass, has increasingly been attracting attention in Japan, which has an aged society. The association between chronic low back pain (CLBP) and muscle mass is important. This study aimed to investigate the effect of exercise therapy for CLBP with or without sarcopenia. METHODS: This study was a prospective cohort study. Patients who were aged >65 years during 2017-2018 and had CLBP, with pain lasting >12 weeks and pain intensity being ≥3, were included in the study. The patients were divided into two groups: sarcopenia (S) and nonsarcopenia (NS) groups. The numerical rating scale (NRS) for pain intensity, Roland-Morris Disability Questionnaire (RMDQ), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Hospital Anxiety and Depression Scale (HADS), trunk muscle strength, a European Quality of Life instrument, and an NRS of treatment satisfaction were assessed. All patients underwent a high-intensity exercise therapy during 2 weeks of hospitalization and were followed up for 1 and 3 months. RESULTS: Twenty-eight patients with CLBP were included. The prevalence rate of sarcopenia was 42.9%. The NRS and RMDQ scores and gait function were clinically improved at the end points in all patients with or without sarcopenia. Moreover, high treatment satisfaction was achieved. The quality of life, treatment satisfaction, psychological disorder subscale score of the JOABPEQ, and HADS score tended to be lower in the S group than in the NS group. CONCLUSIONS: Our short-term exercise therapy was effective for low back pain, disability, and gait disturbance in elderly patients with CLBP with or without sarcopenia. However, the prevalence of sarcopenia was high in elderly patients with CLBP. Although low back pain and disability in patients in the S group were improved by exercise therapy, their quality of life and treatment satisfaction might be lower than those of patients without sarcopenia.

6.
Spine (Phila Pa 1976) ; 45(11): E639-E646, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-31842106

ABSTRACT

STUDY DESIGN: A retrospective study of a randomized clinical trial and a prospective study of patients with lumbar spinal stenosis (LSS). OBJECTIVE: The aim of this study was to identify the effects of the number of physical therapy (PT) sessions on clinical outcomes of patients with LSS. SUMMARY OF BACKGROUND DATA: Supervised PT for patients with LSS has been reported to lead to better short-term outcomes in terms of disability and leg pain than unsupervised exercise. However, no studies have investigated the relationship between the number of PT sessions and the therapeutic effects in patients with LSS. METHODS: All patients received exercise therapy for 6 weeks. Included were 43 patients receiving supervised PT twice a week (P2 group), 38 patients receiving supervised PT once a week (P1 group), and 43 patients receiving a home exercise program alone (HE group). Clinical outcomes were measured using the Zurich Claudication Questionnaire (ZCQ), a numerical rating scale (NRS) of back pain and leg pain, the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) at baseline and at 6 weeks. RESULTS: At 6 weeks, the P2 group showed significant improvements in ZCQ physical function, back and leg pain on the NRS compared with the P1 group (P < 0.05). Compared with the HE group, the P2 group showed significant improvements in ZCQ symptom severity and physical function, back and leg pain on the NRS, and JOABPEQ gait disturbance (P < 0.05). There were no significant differences in mean changes after 6 weeks between the P1 and HE groups. CONCLUSION: Six weeks of supervised PT twice a week resulted in significant short-term improvements in symptom severity, physical function, back and leg pain, and gait disturbance compared with once a week and/or home exercise alone. Patients with LSS should be treated with intensive and supervised exercise programs to obtain maximum benefit of exercise therapy. LEVEL OF EVIDENCE: 3.


Subject(s)
Exercise Therapy/methods , Lumbar Vertebrae , Pain Measurement/methods , Spinal Stenosis/diagnosis , Spinal Stenosis/therapy , Aged , Aged, 80 and over , Back Pain/diagnosis , Back Pain/physiopathology , Back Pain/therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Physical Therapy Modalities , Prospective Studies , Retrospective Studies , Spinal Stenosis/physiopathology , Surveys and Questionnaires
7.
Spine J ; 19(8): 1310-1318, 2019 08.
Article in English | MEDLINE | ID: mdl-30986577

ABSTRACT

BACKGROUND CONTEXT: Exercise has been reported to improve short-term outcomes for patients with LSS in terms of disability and back and leg pain. However, no studies have compared supervised exercise with unsupervised exercise or quantified physical activity using a pedometer to confirm compliance with a home exercise program. PURPOSE: To compare the effectiveness of supervised physical therapy (PT) with unsupervised exercise for patients with lumbar spinal stenosis (LSS). STUDY DESIGN/SETTING: A single-center, open-label, randomized controlled trial. PATIENT SAMPLE: Patients presenting with symptoms of neurogenic claudication caused by LSS, which was confirmed by magnetic resonance imaging. OUTCOME MEASURES: The primary outcome was improvement in symptom severity scores on the Zurich Claudication Questionnaire (ZCQ) at 6 weeks. Secondary outcomes included physical function on the ZCQ, self-paced walking test (SPWT) performance, pain indicated using a numerical rating scale (NRS), and the number of daily steps measured by pedometer. METHODS: Patients with LSS were randomized to a PT group, who performed supervised PT twice a week for 6 weeks, or a home exercise (HE) group. PT sessions included manual therapy, individually tailored stretching and strengthening exercises, cycling, and body weight-supported treadmill walking. RESULTS: Forty-three patients were randomly allocated to the PT group and 43 patients to the HE group. Compared with the HE group, the PT group had greater percentage of responders achieving minimum clinically important difference in ZCQ symptom severity (difference for percentage between groups [95%confidence interval], 30.2% [9.1-48.6], p=.01), ZCQ physical function (32.6% [11.6-50.6], p<.01), walking distance on the SPWT (39.5% [18.8-56.7], p<.01), leg pain on the NRS (34.9% [13.9-52.7], p<.01), and number of daily steps (25.6% [4.9-43.9], p=.01). CONCLUSIONS: Supervised PT for patients with LSS resulted in significant short-term improvements in symptom severity, physical function, walking distance, pain, and physical activity compared with unsupervised exercise.


Subject(s)
Exercise Therapy/methods , Lumbar Vertebrae/physiopathology , Spinal Stenosis/therapy , Aged , Exercise Therapy/adverse effects , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Pain/etiology , Surveys and Questionnaires , Walking
8.
J Nutr Sci Vitaminol (Tokyo) ; 58(5): 371-5, 2012.
Article in English | MEDLINE | ID: mdl-23327974

ABSTRACT

The effects of betaine supplementation on non-alcoholic steatohepatitis (NASH) model mice were examined by measuring the accumulation of fat in the livers of NASH model mice compared to a control. Betaine from sugar beets was provided to the model mice as a dietary supplement. After 3 wk of dietary supplementation, there were no significant differences in body weight or liver weight between the groups. However, the liver to body weight ratio in the high-fat diet with betaine (HFB) group was significantly (p<0.05) higher than that in the high-fat diet (HF) group. There were no differences in serum triglyceride (TG) concentrations, AST and ALT activities, or hepatic glutathione concentrations between the groups. Hepatic TG level in the HFB group was significantly (p<0.05) lower than that in the HF group. Hepatic cells obtained from the HF group showed increased occurrence of explosive puff and necrosis as compared with those in the HFB group. Betaine supplementation had an inhibitory effect on fat accumulation in the liver: the Oil red-positive area in the HFB group (0.82 ± 0.85%) was significantly (p<0.001) smaller than that in the HF group (9.06 ± 2.24%). These results indicate the potential of betaine to serve as an agent for amelioration of hepatic steatosis in NASH model mice.


Subject(s)
Betaine/pharmacology , Dietary Supplements , Fatty Liver/drug therapy , Alanine Transaminase/blood , Animals , Body Weight , Diet, High-Fat , Dietary Fats/administration & dosage , Disease Models, Animal , Glutamyl Aminopeptidase/blood , Glutathione/analysis , Hepatocytes/drug effects , Hepatocytes/metabolism , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease , Organ Size , Triglycerides/blood
9.
Neurosci Lett ; 402(1-2): 167-72, 2006 Jul 10.
Article in English | MEDLINE | ID: mdl-16644120

ABSTRACT

Intracolonic (i.col.) administration of the PAR2-activating peptide (PAR2AP) SLIGRL-NH2 slowly develops visceral hypersensitivity to i.col. capsaicin in ddY mice. Thus, we further analyzed roles of PAR2 in colonic hypersensitivity, using the novel potent PAR2AP, 2-furoyl-LIGRL-NH2 and PAR2-knockout (KO) mice. In ddY mice, i.col. 2-furoyl-LIGRL-NH2 produced delayed (6 h later) facilitation of capsaicin-evoked visceral nociception, an effect being much more potent than SLIGRL-NH2. Such effects were mimicked by i.col. trypsin. In wild-type (WT), but not PAR2-KO, mice of C57BL/6 background, i.col. PAR2 agonists caused delayed facilitation of sensitivity to capsaicin. The PAR2-triggered visceral hypersensitivity was abolished by a bradykinin B2 receptor antagonist, HOE-140. Our data thus provide ultimate evidence for role of PAR2 in colonic hypersensitivity, and suggest involvement of the bradykinin-B2 pathway.


Subject(s)
Bradykinin/metabolism , Colon/physiopathology , Hyperalgesia/pathology , Oligopeptides/administration & dosage , Receptor, PAR-2/physiology , Animals , Capsaicin/pharmacology , Colon/drug effects , Dose-Response Relationship, Drug , Drug Interactions , Hyperalgesia/chemically induced , Hyperalgesia/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Oligopeptides/pharmacology , Pain Measurement/methods , Receptor, PAR-2/agonists , Receptor, PAR-2/deficiency , Time Factors , Trypsin/pharmacology
10.
Arterioscler Thromb Vasc Biol ; 25(7): 1376-82, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15879304

ABSTRACT

OBJECTIVES: We performed a detailed kinetic analysis in a rat balloon injury model to clarify the essential roles of alphavbeta3 integrin and endothelial cell (EC) regeneration in neointima formation. Using this model, we evaluated the antistenotic effect of Dainippon compound BS-1417, a novel alphavbeta3 integrin antagonist. METHODS AND RESULTS: Kinetic analysis using RT-PCR showed that alphavbeta3 integrin-related genes are upregulated before neointima formation. Morphological and functional analyses revealed that EC regeneration requires >4 weeks after injury, and that recovery of EC normal function coincides with the arrest of neointima formation. Subcutaneous infusion of BS-1417 for 2, 4, 7, or 12 weeks after injury potently inhibited neointima formation without affecting EC regeneration. Although withdrawal of treatment with BS-1417 after short-term administration after injury resulted in catch-up growth of neointima, a long-term study suggested that this catch-up growth can be prevented by continuous administration of BS-1417 until EC regeneration. CONCLUSIONS: We clarified that alphavbeta3 integrin and EC regeneration play an essential role in neointima formation, and that continuous administration of BS-1417 potently and stably inhibits neointima formation without affecting EC regeneration. These findings suggest that BS-1417 might be useful as a novel systemic drug for the treatment of restenosis.


Subject(s)
Angioplasty, Balloon/adverse effects , Carotid Artery Injuries/drug therapy , Carotid Artery Injuries/pathology , Carotid Stenosis/therapy , Integrin alphaVbeta3/antagonists & inhibitors , Piperazines/pharmacology , Animals , Carotid Arteries/drug effects , Carotid Arteries/pathology , Carotid Arteries/physiology , Carotid Stenosis/pathology , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Endothelium, Vascular/physiology , Gene Expression/drug effects , Integrin alphaVbeta3/genetics , Male , Rats , Rats, Sprague-Dawley , Regeneration/drug effects , Time Factors , Tunica Intima/drug effects , Tunica Intima/pathology , Tunica Intima/physiology , Up-Regulation/drug effects
11.
Bioorg Med Chem Lett ; 14(10): 2567-70, 2004 May 17.
Article in English | MEDLINE | ID: mdl-15109653

ABSTRACT

A new series of phenylpiperazine-based derivatives with strong antagonistic activity for alpha v beta 3 integrin were synthesized. Of these derivatives, the fluorine-substituted compound 8 showed strong inhibitory activity and high selectivity for alpha v beta 3 integrin receptor (IC(50) = 0.055 nM). In vivo evaluation of the antistenotic effects of 8 indicated that this compound significantly inhibits neointima formation in rat balloon injury model.


Subject(s)
Angioplasty, Balloon/adverse effects , Integrin alphaVbeta3/antagonists & inhibitors , Piperazines/therapeutic use , Tunica Intima/drug effects , Animals , Carotid Arteries/drug effects , Constriction, Pathologic/drug therapy , Dose-Response Relationship, Drug , Inhibitory Concentration 50 , Models, Animal , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Piperazines/blood , Piperazines/chemical synthesis , Rats , Tunica Intima/growth & development
12.
J Pharmacol Sci ; 94(3): 277-85, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15037813

ABSTRACT

Protease-activated receptors (PARs) 1 and 2 are expressed in capsaicin-sensitive sensory neurons, being anti- and pro-nociceptive, respectively. Given the possible cross talk between PAR-2 and capsaicin receptors, we investigated if PAR-2 activation could facilitate capsaicin-evoked visceral pain and referred hyperalgesia in the mouse and also examined the effect of PAR-1 activation in this model. Intracolonic (i.col.) administration of capsaicin triggered visceral pain-related nociceptive behavior, followed by referred hyperalgesia. The capsaicin-evoked visceral nociception was suppressed by intraperitoneal (i.p.) TFLLR-NH2, a PAR-1-activating peptide, but not FTLLR-NH2, a control peptide, and unaffected by i.col. TFLLR-NH2. SLIGRL-NH2, a PAR-2-activating peptide, but not LRGILS-NH2, a control peptide, administered i.col., facilitated the capsaicin-evoked visceral nociception 6-18 h after administration, while i.p. SLIGRL-NH2 had no effect. The capsaicin-evoked referred hyperalgesia was augmented by i.col. SLIGRL-NH2, but not LRGILS-NH2, 6-18 h after administration, and unaffected by i.p. SLIGRL-NH2, and i.p. or i.col. TFLLR-NH2. Our data suggest that PAR-1 is antinociceptive in processing of visceral pain, whereas PAR-2 expressed in the colonic luminal surface, upon activation, produces delayed sensitization of capsaicin receptors, resulting in facilitation of visceral pain and referred hyperalgesia.


Subject(s)
Capsaicin/adverse effects , Hyperalgesia/chemically induced , Pain/chemically induced , Receptor, PAR-1/metabolism , Receptor, PAR-2/metabolism , Viscera/drug effects , Administration, Rectal , Animals , Behavior, Animal/drug effects , Capsaicin/administration & dosage , Capsaicin/antagonists & inhibitors , Colon/drug effects , Colon/innervation , Dose-Response Relationship, Drug , Drug Synergism , Drug Therapy, Combination , Hyperalgesia/complications , Hyperalgesia/physiopathology , Injections, Intraperitoneal , Male , Mice , Oligopeptides/administration & dosage , Oligopeptides/chemistry , Oligopeptides/pharmacokinetics , Pain/complications , Pain/physiopathology , Pain Measurement/methods , Peptides/administration & dosage , Peptides/pharmacokinetics , Receptor, PAR-1/drug effects , Receptor, PAR-1/genetics , Receptor, PAR-2/drug effects , Receptor, PAR-2/genetics , Time Factors , Up-Regulation , Viscera/innervation , Viscera/physiopathology
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