Neuropathic pain

• Bennett (Planter mechanical stimulation, Planter thermal stimulation, Sensation stimulation)
• Chung (Planter mechanical stimulation, Planter thermal stimulation)
• Selzter (Planter mechanical stimulation, Planter thermal stimulation)

Neuropathic pain is a chronic painful disorder that manifests following peripheral/central neuropathy caused by physical disorder or due to functional disorder. We have extensive experience with Bennet, Chung, and Selzter models and are capable of preparing stable models.

Streptozotocin -induced (STZ) pain hypersensitivity (Planter mechanical stimulation)

Diabetic neuropathy is a diabetic complication and manifests earliest among the 3 main complications. Type 1 diabetes is induced by administration of streptozocin (STZ) for assessment of hypernociception.

Adjuvant induced hyperalgesia (Randall-Selitto)

The adjuvant-induced model is a model targeting pain due to systemic inflammation. It is widely used for screening/assessment of pain or anti-inflammatory drugs.

Carrageenin induced hyperalgesia (Randall-Selitto)

The carrageenan-induced model is a model targeting pain due to edema. It is widely used for screening/assessment of pain or anti-inflammatory drugs.

Anti-cancer agent-induced pain hypersensitivity (Planter mechanical stimulation, Sensation stimulation)

Taxane preparations including paclitaxel, vinca alkaloid preparations including vincristine, and platinum complex preparations including cisplatin and oxaliplatin cause adverse reactions due to peripheral neuropathy (numbness, sensory disturbance, pain) at high incidence.

Cancer pain model (Metastatic bone tumor)

Cancer pain, markedly impairing the patient QOL (Quality of life), needs to be controlled adequately. Using the bone metastasis model prepared by transplantation of rat breast cancer cell line MRMT-1 into the tibia of the same strain rat, we evaluate cancer pain.

Pain hypersensitivity of low temperature burns

Postoperative pain hypersensitivity (Planter mechanical stimulation)

Osteoarthritis (MIA-induced, weight distribution in hindlimb, mechanical stimulation of sole, heat stimulation)

Osteoarthritis (OA) is a disease characterized by degeneration and loss of articular cartilages and a lifestyle disease of the highest incidence among bone/joint diseases. We have a model of OA induced by administration of sodium monoiodoacetate (MIA) into the knee joint cavity.

Specific Alternation of Rhythm in Temperature (Fibromyalgia model, Planter mechanical stimulation)

Fibromyalgia of which cardinal symptom is cryptogenic generalized pain (wide-spread pain) with subsidiary symptoms including neuropsychiatric symptoms such as insomnia and depression, and autonomic nervous system symptoms such as irritable bowel syndrome and overactive bladder. The cold stress model is widely used as a fibromyalgia model.

Scopolamine-induced amnesia

Animals are housed in an operant-conditioning chamber equipped with levers and allowed to learn obtaining reward (tablet-type feed) by pressing the lever. Using this behavior, the effect of a drug on short-term memory can be assessed.

Lesions in the nucleus basalis of meynert model

4-vessel occlusion (4VO) model

Elevated plus maze test

The elevated plus-maze test (mice and rats), which was developed as an anxiety test method, can be used to evaluate the anxiolytic effects of test substances.

Social interaction test

Kainic acid-induced seizure model

The kainic acid-induced seizure model is a model presenting status epilepticus where epileptic seizure persists intermittently over several hours, prepared by intraperitoneal administration of kainic acid which strongly excites the glutamatergic neuron.

Pilocarpine-induced model

The pilocarpine-induced epilepsy model is a model of temporal lobe epilepsy induced by intraperitoneal administration of pilocarpine hydrochloride, a nonselective muscarinic receptor agonist.

Transient middle cerebral artery occlusion

Using the rat cerebral ischemia model by transient middle cerebral artery (MCA) occlusion, the efficacy of the test substance is assessed based on the volume of cerebral infarct area, neurological symptoms, or the results of the rotarod test as the indices. We have extensive experience in this field and are capable of preparing stable models.

Methamphetamine-induced hyperactivity (Schizophrenia)

Alcohol-induced movement disorder

Forced swimming test (Immobility time)

The anti-depression-like effect of a drug is assessed based on duration of immobility as the index when the animal is forced to swim in water (forced swim). The forced swim test is performed under the conditions designed to fit the experimental environment of our company while still following the original method and has been conducted and observed by our company extensively.

Tail suspension test (Immobility time)

The anti-depression-like effect of a drug is assessed based on duration of immobility as the index when the animal is suspended with the tail fixed (tail suspension). We have extensive background data from the tail suspension test where varying mouse strains and their drug sensitivities resulting in depression-like behavior were investigated.

Reserpine-induced hypothermia

Lipopolysaccharide-induced depression

Antidepressant-like effects of the drug are evaluated using a depression model (mouse) created by administering lipopolysaccharide (LPS) as an indicator of forced swimming and tail suspension immobility time.

Treadmill fatigue test

6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (rat)

Test using ALS model (rat)

*Prior consultation is necessary for procurement of animals.

Neonatal HIE model (rat)

Using the HIE model created, the efficacy of the drug is examined by the cylinder test, Morris water maze, etc. as indices.

Spontaneous hypertention

Spontaneously hypertensive rats (SHR) can be used to study the antihypertensive or prophylactic effects of the test substance. Blood pressure measurements are performed using a non-heating/non-invasive blood pressure monitor for rats and mice.

Hypertension induced by ligation of renal artery

Salt-loaded hypertension (Dahl rats)

Dahl rats develop hypertension spontaneously when fed a high salt diet. The spontaneous hypertension model (Dahl rats) can be used to study the antihypertensive or prophylactic effects of drugs. Blood pressure is measured using a non-heating/non-invasive blood pressure monitor, but can also be measured using a catheter transducer.

Cardiac infraction (Permanent ligation / ishcemia-reperfusion), Cardiac failure (chronic phase)

Cardiac disease is evaluated by the acute phase assessment for consideration of the therapy at the time of onset of myocardial infarction similar to that in clinical practice and by the chronic phase assessment for investigation of prognosis for prevention of cardiac failure and for life prolonging effect. We also undertake tests in the field of regenerative medicine.

Calcium chloride-induced

Abdominal aortic aneurysm (AAA) is a highly lethal disease when left untreated and surgery is said to be the only treatment. We have a calcium chloride-induced AAA model. This model enables measurement of the abdominal aorta diameter using the ultrasonograph.

Ligation of femoral artery

Peripheral arterial disease (PAD) is frequently found in diabetic patients and elderly people, and when the disease becomes severe, leg amputation is inevitable, which leads to marked decrease of QOL (Quality of Life). The hindlimb ischemia model is widely used as the PAD model and frequently employed in studies not only on drugs but also on the regenerative effect of cell components such as bone marrow mononuclear cells.

Aortic arch stenosis model

Citric acid- or capsaicin-induced

Lipopolysaccharide (LPS) Exposure (Acute)

Acute respiratory distress syndrome (ARDS) is a type of respiratory failure that occurs suddenly in patients with clinically severe conditions. In particular, the conditions before and after the onset of the disease are referred to as acute lung injury. We create an acute lung injury model by inhalation of lipopolysaccharide (LPS).

Bleomycin-induced pulmonary fibrosis model

Idiopathic pulmonary fibrosis is a lung disease consisting primarily in severe fibrosis of the lung. The lung disease has poor response to steroids or immunosuppressive agents and poor prognosis. We prepare the bleomycin-induced pulmonary fibrosis model.

Spontaneous diabetes model

STZ-induced type I diabetes nephropathy model

Systemic lupus erythematosus (SLE) model

Systemic lupus erythematosus (SLE) is an autoimmune disease where inflammation of unknown origin occurs in organs in the body, being classified as a collagen disease. Both MRL/lpr mice and NZBWF1 mice are known to have SLE-like lupus nephritis spontaneously and the animals are widely used as SLE models.

Chronic GVHD Model

Graft-versus-host disease (GVHD) is a general term for a condition in which the immune response of a donor (organ donor) organ attacks the recipient (patient). The mouse model of chronic GVHD develops lupus nephritis-like symptoms.

Adenine-induced renal failure

The adenine renal failure model develops hyperphosphatemia secondary to adenine loading, resulting in severe renal failure.

Pyuromycin nephritis

Nephrosis can be induced in rats by administration of puromycin.

Renal ischemia-reperfusion model

Acute renal injury occurs when a state of reperfusion develops from decreased renal blood flow due to cardiac failure, dehydration, hemorrhage, or renal artery stenosis or occlusion.

Overactive bladder

Dysuria in spinal cord

Cystitis (hydrochloric acid, cyclophosphamide, acetic acid-induced, or hydrogen peroxide-induced)

Lower urinary tract symptoms (benign prostatic hyperplasia)

Stress urinary incontinence

Carrageenin-induced edema

The carrageenan-induced model is a model targeting pain due to edema. It is widely used for screening/assessment of pain or anti-inflammatory drugs.

Yeast-induced pain

Adjuvant arthritis

The adjuvant-induced model is a model targeting pain due to systemic inflammation. It is widely used for screening/assessment of pain or anti-inflammatory drugs.

Type II collagen-induced arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease based on abnormal immune function, of which cardinal symptoms are polyarthritis and joint symptoms such as rapidly progressive joint destruction. This model prepared by immunization with type II collagen to induce arthritis is widely used as an arthritis model.

Osteoarthritis (MIA induced, hindlimb weight distribution, plantar mechanical stimulation)

Osteoarthritis (OA: Osteoarthritis) is a disease characterized by degeneration and loss of cartilage in joints and is one of the most frequent lifestyle diseases among bone and joint diseases. We have an OA model created by monoiodoacetate sodium salt (MIA) administered into the knee joint cavity.

UV-induced erythema

We are able to produce a guinea pig model of erythema by UV irradiation and evaluate the drug efficacy of test substances using skin reaction scores as parameters.

Spontaneous atopic dermatitis

Pruritus observed in atopic dermatitis and other conditions significantly reduces quality of life (QOL). We maintain a conventional housing environment and have a pathological model of spontaneous onset of atopic dermatitis by housing NC mice in a conventional environment.

Allergic encephalomyelitis (EAE) model (Score evaluation)

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune model induced by immunization with protein antigens and peptides derived from central nervous tissue, and is similar to Multiple Sclerosis (MS) and is used for research on MS, etc., as its pathological symptoms are similar to those of Multiple Sclerosis (MS). We have two types of sclerosis models: the relapse-remission type model (SJL mice) and the chronic model (C57BL mice).

X ray-induced oral mucositis model

Passive cutaneous anaphylaxis (PCA) Type I

Delayed type hyper responsiveness, Type IV

Pruritic response (Substance P-induced/development of spontaneous dermatitis)

Pruritus is an unendurable impulse caused by various factors. We have scratching activity models induced by chemicals. These models enable objective evaluation of scratching activities caused by chemicals using the scratching measuring system.

OVA-induced allergic conjunctivitis

DNP-Ascaris-induced allergic conjunctivitis

Ragweed pollen-induced allergic conjunctivitis

Pylorus-ligated gastric ulcer

Aspirin-induced gastric ulcer

Indomethacin-induced gastric ulcer

Dextran sulfate sodium-induced coitis

Ulcerative colitis is a nonspecific inflammatory disease where ulcer and erosion are formed mainly on the colonic mucosa. The DSS-induced colitis model is widely used as the model of ulcerative colitis.

Measurement by telemetry of gastrointestinal motility in unanesthetized and unrestrained conditions

Using a telemeter designated for gastrointestinal motility and the PowerLab system, the effects of test substances on gastrointestinal motility can be investigated by measuring gastrointestinal motility in the gastric body, gastric antrum, duodenum, and jejunum in unanesthetized and unrestrained dogs under fasting conditions.

Enteral infusion high-speed injection load diarrhea

Defecation (enema)

Difficulty in defecation and fecal incontinence significantly reduce quality of life. It is estimated that there are approximately 5 million potential patients with fecal incontinence in Japan, and it is predicted that the number of patients will increase further due to the aging of the population. Currently, drug treatments are inadequate, and the development of new treatments is desired. Screening using model animals is important for the development of new therapeutic agents, but until now, only experimental designs using small animals under anesthesia were available.
We have established a gastrointestinal and internal anal sphincter measurement system in dogs using a gastrointestinal motility measurement system, which enables us to examine the effects of test substances on internal anal sphincter motility under consicous conditions that better reflect biological responses.

Low-fiber diet

Morphine (Dihydrocodeine)

Ligature

This experimental system is a method to evaluate the inhibitory effect of the test substance on esophageal mucosal damage using a rat model of reflux esophagitis.

Thioacetamide-induced liver fibrosis

Thioacetamide (TAA) is metabolized in the liver and this process is known to produce hepatic disorder. The disorder resembles human liver fibrosis in its histopathological findings in the hepatic hilus and biochemical changes in the blood. We conduct pre-clinical studies on thioacetamide-induced liver fibrosis in order to develop drugs that improve liver function.

D-galactosamine-induced hepatitis

D-galactosamine is specifically metabolized in the liver and this process is known to produce hepatic disorder. The disorder resembles human viral hepatitis in its histopathological findings in the liver and biochemical changes in the blood, and has been used in general use along with carbon tetrachloride-induced models. This study system is designed to search for the effects of various test substances for hepatoprotective effects in the D-galactosamine-induced acute liver injury model.

Concanavalin A (ConA) induced liver injury

Non-alcoholic steatohepatitis (NASH)

Non-alcoholic steatohepatitis (NASH) is a pathological condition showing alcoholic steatohepatitis-like chronic hepatic disorder in spite of absence of drinking history. We have developed a unique NASH model accompanied with hepatic fibrogenesis and hyperlipidemia.

Carbon tetrachloride-induced hepatitis (acute, chronic)

Models of cut, skin defect, and decubitus - bedsore -

Models of erythema - UV irradiation -, moisture retention, decreased collagen synthesis, and skin pigmentation

Sunburn can be divided into two types: "sunburn" in which the skin is exposed to ultraviolet (UVB) rays from the sun, causing erythema within minutes to hours, and "suntan" in which melanin pigmentation occurs several days after the sunburn has disappeared. We conduct evaluation studies of test substances using pigmented guinea pigs as a model of pigmentation caused by UV irradiation.

Type-1 and type-2 diabetes model

Diabetes causes complications including neuropathy, nephropathy, and cataract. It is very important to control blood glucose level for control of onset of complications. We have extensive experience with the streptozotocin (STZ)-induced type-1 diabetes model and models of type-2 diabetes typically in ZDF, GK rats, db/db, and KK-Ay mice; thus are able to deal with any strain.

High-calorie diet loading

Obesity represents abnormal energy metabolism characterized by the imbalance between energy taken and energy consumed, being a cause of many lifestyle diseases. We have the obesity model prepared by loading high-calorie diet (diet-induced obesity (DIO)).

Respiratory metabolism measurement

Metabolic syndrome is a condition where hyperglycemia, dyslipidemia, and hypertension are caused with visceral fat accumulation as the common factor, possibly leading to life-threatening diseases when two or more such diseases occur concurrently. Prevention/improvement through diet modification and exercise is important and therapeutic agents for obesity are actively being developed. Respiratory quotient and energy consumption estimated by measurement of respiratory metabolism are important indices to assess the anti-obesity effect.

Oral glucose tolerance test (OGTT), Insulin tolerance test (ITT)

Spontaneous

High-cholesterol diet loading

Corn oil emulsion loading (inhibition of digestion-absorption of lipid)